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J Hilsted

Publications and source records attributed to J Hilsted.

At least 19 recordsLinked to original sources
PubMed2002

Minor long-term changes in weight have beneficial effects on insulin sensitivity and beta-cell function in obese subjects.

AIM: To evaluate the long-term effect of changes in body composition induced by weight loss on insulin sensitivity (SI), non-insulin mediated glucose disposal, glucose effectiveness (SG)and beta-cell function. DESIGN: Glucose metabolism was evaluated before and after participation in a two-year weight loss trial of Orlistat vs. placebo, combined with an energy and fat restricted diet. SUBJECTS: Twelve obese patients (11 women, 1 man), age 45.8 +/- 10.5 years, body weight (BW) 99.7 +/- 13.3 kg, BMI 35.3 +/- 2.8 kg/m(2). MEASUREMENTS: At inclusion and 2 years later an oral glucose tolerance test (OGTT) and a frequently sampled intravenous glucose tolerance test (FSIGT) were performed. Body composition was estimated by a dual-energy X-ray absorptiometry (DXA) whole body scanning. RESULTS: The patients obtained varying changes in BW ranging from a weight loss of 17.8 kg to a weight gain of 6.0 kg. Corresponding changes in fat mass (FM) varied from a 40% reduction to a19% increase. A significant decrease in both fasting (p = 0.038) and 2 h (p = 0.047) blood glucose at OGTT was found. The improvement in insulin sensitivity (SI) estimated by means of Bergmans Minimal Model, was significantly and linearly correlated to change in total FM (r = - 0.83,p = 0.0026). A multiple regression analysis showed that changes in truncal FM was the strongest predictor of change in S(I) explaining 67% of the variation. First phase insulin response (AIRg)remained unchanged whereas insulin disposition index increased significantly (p = 0.044). At inclusion five patients had impaired glucose tolerance of which four, who lost weight, were normalized at the retest 2 years later. CONCLUSION: In obese subjects long-term minimal or moderate changes in weight were found to be linearly associated with changes in insulin sensitivity. In obese subjects with impaired glucose tolerance even a minor weight loss was able to normalize glucose tolerance.

Absorptiometry, Photon↗
PubMed2002

Body composition in adults with Type 1 diabetes at onset and during the first year of insulin therapy.

AIMS: To describe body composition in patients with Type 1 diabetes at diagnosis and during the first year after initiation of insulin therapy. RESEARCH DESIGN AND METHODS: In 10 (eight male and two female) newly onset Type 1 patients, age 31.5 +/- 3.2 years (27-37 years) (sd and range), body mass index (BMI) 20.8 +/- 1.6 (19.2-23.4) kg/m2, body composition was estimated by means of dual-energy X-ray absorptiometry (DXA) whole body scanning supplemented by estimation of total body water (TBW) (isotope dilution technique with 3H2O) at diagnosis and after 1, 3, 6 and 12 months of insulin therapy. RESULTS: During the first year after onset of diabetes body weight (BW) increased 4.3 +/- 2.9 (0.1-8.3) kg (P = 0.0012) distributed as a 13.3% (1.6 kg) increase in total fat mass (FM) and 4.9% (2.5 kg) increase in lean body soft tissue mass (LBM). The self-reported weight loss at onset was 6.3 +/- 2.5 kg (1.5-10.0 kg). Compared with two reference populations the Metropolitan Life Insurance Co. and a healthy age and sex-matched local DXA scanned group the initial body composition data demonstrated BW 6.2 kg below ideal weight and a significant reduction of the FM (25% or -0.87 sd), whereas LBM was within the expected range. CONCLUSIONS: During the first year after onset of Type 1 diabetes the mean increase in BW is 6.5% with a 13.3% increase in FM and a 4.9% increase in LBM. Self-reported data on premorbid BW suggest an approximately 10% reduction in BW at onset of Type 1 diabetes. Compared with a healthy reference population initial body composition data demonstrate a 25% reduction of the FM, whereas only a minor and non-significant reduction in the LBM is encountered. These data indicate that uncontrolled diabetes is rather a fat catabolic state than, as previously believed, a protein catabolic state.

Absorptiometry, Photon↗
PubMed2001

Predictors of weight loss and maintenance during 2 years of treatment by sibutramine in obesity. Results from the European multi-centre STORM trial. Sibutramine Trial of Obesity Reduction and Maintenance.

BACKGROUND: In this report we assess pre-treatment determinants of weight loss and maintenance outcome in The Sibutramine Trial of Obesity Reduction and Maintenance (STORM), a 2 y randomized, double-blind, placebo-controlled, European multicenter study examining the effect of sibutramine (Sib) on inducing and maintaining weight loss in obese subjects. MATERIAL: A total of 605 obese patients (BMI: 30-45 kg/m2) of both gender were included from eight European centers and treated for 24 months. The patients were treated for the initial 6 months by Sib (10 mg/day) and a low-fat low-energy, individualized diet (600 kcal/day deficit). The 467 patients who achieved >5% weight loss after 6 months were randomized 3&ratio;1 to Sib (10 mg/day) (Sib/Sib) and placebo (Sib/Pla) for weight maintenance over a further 18 months. MAIN OUTCOME AND ANALYSES: Pre-treatment individual characteristics were assessed as predictors of 6 months weight loss (kg) and 24 months weight maintenance using simple and multivariate correlation and regression analyses. RESULTS: In univariate analyses, the 6 month weight loss (n=505) was positively associated with pre-treatment body weight (r=0.27), height (r=0.18), fat-free mass (r=0.21) (all P<0.001), fat mass (r=0.13, P<0.03), and resting metabolic rate (r=0.13, P<0.003). However, no relation was found with age, gender, smoking status, age at onset of obesity, or number of previous slimming attempts. The same predictors were found for weight change to endpoint in the Sib/Sib group (n=350), while no predictors were identified in the Sib/Pla (n=114). In the multivariate regression analysis only pre-treatment body weight predicted weight loss at 6 months (P<0.001). Weight change (kg) to 24 month was predicted by: 4.34+0.07*body weight (kg)-4*treatment (Sib=1, Pla=0)-0.06*age (y), (r2=8%, P<0.001). CONCLUSION: Only pre-treatment body weight seems to be an important independent predictor of 6 months weight loss and 24 month weight maintenance in this study on diet and Sib. As only 8% of the variation in 24 months weight change could be explained by the predictors, the clinical value of this information is limited.

Adolescent↗
PubMed2001

Neuroendocrine responses to hypoglycaemia decrease within the first year after diagnosis of type 1 diabetes.

Neuroendocrine responses (adrenaline, noradrenaline and pancreatic polypeptide (PP)) to hypoglycaemia are often diminished in long-term diabetic patients, but the role of autonomic nervous system changes in these reductions is not yet fully clarified. In order to establish whether such changes in neuroendocrine responses occur early in the course of diabetes, we investigated the responses to insulin-induced hxypoglycaemia during the first year of type 1 diabetes. Autonomic and somatic nerve function tests were performed concomitantly. Six type 1 diabetes patients were studied 3 and 12 months after diagnosis of diabetes. Hypoglycaemia was induced by i.v. insulin infusion after an overnight normalization of blood glucose. Autonomic nerve function was evaluated by cardiovascular tests, and somatic nerve function by nerve conduction velocities A 50% reduction was found in adrenaline (p < 0.025) and noradrenaline (p < 0.05) responses to hypoglycaemia; PP, too, was significantly diminished at 12 months compared with 3 months after diagnosis of type 1 diabetes. Rate of glucose recovery did not differ at month 12 compared with month 3. Cardiovascular autonomic nerve function tests did not change and remained within the normal range throughout the study. Altered neuroendocrine responses to hypoglycaemia may occur early in the course of type 1 diabetes. These are unlikely to be due to structural changes (i.e. autonomic neuropathy), but rather to changes in central nervous system activity patterns, i.e. a higher threshold (i.e. a lower blood glucose level) for hypothalamic activation of the sympathoadrenal system.

Adult↗
PubMed2001

Gene expression of a truncated and the full-length growth hormone (GH) receptor in subcutaneous fat and skeletal muscle in GH-deficient adults: impact of GH treatment.

In humans at least two GH receptors are significantly expressed. One is the full-length receptor (GHR); the other is a truncated form (GHRtr), that lacks most of the intracellular domain. This receptor may inhibit the action of the full-length receptor. Circulating GH-binding protein (GHBP) is a proteolytically cleaved product from both of these receptors. The clinical relevance of the different receptor types is unknown. We examined the gene expression of GHR and GHRtr in human adipose tissue and skeletal muscle and the influence of GH treatment on this expression. Furthermore, we studied the relationship of circulating GHBP and body composition to GHR and GHRtr gene expression. Eleven adult GH-deficient patients were studied before and after 4 months of GH substitution therapy. Abdominal fat obtained by liposuction and femoral muscle biopsies were taken at baseline and after 4 months. Gene expression of GHR and GHRtr in adipose tissue and skeletal muscle was determined and expressed relative to the expression of beta-actin. Gene expression of GHR in abdominal sc adipose tissue was not altered, whereas the expression of GHRtr increased significantly. In skeletal muscle inverse changes were seen in the expression of messenger ribonucleic acid (mRNA) levels for the two GH receptor forms: expression of GHR increased significantly, whereas mRNA levels for GHRtr decreased. As expected, body composition changed with reduction of body fat mass after 4 months of GH treatment. Levels of circulating GHBP decreased significantly. We conclude that GH treatment in GH-deficient adults changes the expression of mRNA for GHR and GHRtr in adipose tissue and skeletal muscle. Whether these changes are responsible for the observed changes in body composition in response to GH treatment and the observed changes in levels of circulating GHBP, however, needs further elucidation.

Adipose Tissue↗
PubMed2000

The effect of 30 months of low-dose replacement therapy with recombinant human growth hormone (rhGH) on insulin and C-peptide kinetics, insulin secretion, insulin sensitivity, glucose effectiveness, and body composition in GH-deficient adults.

The aim of the present study was to evaluate the long-term (30 months) metabolic effects of recombinant human GH (rhGH) given in a mean dose of 6.7 microg/kg x day (= 1.6 IU/day), in 11 patients with adult GH deficiency. Glucose metabolism was evaluated by an oral glucose tolerance test and an iv (frequently sampled iv glucose tolerance test) glucose tolerance test, and body composition was estimated by dual-energy x-ray absorptiometry. Treatment with rhGH induced persistent favorable changes in body composition, with a 10% increase in lean body mass (P < 0.001) and a 12% reduction of fat mass (P < 0.002); however, the glucose tolerance deteriorated significantly, and three patients developed impaired glucose tolerance. Fasting insulin level (P < 0.003) and the homeostasis model assessment insulin resistance score increased significantly, indicating a deterioration in insulin sensitivity; whereas the insulin sensitivity index, calculated from the frequently sampled iv glucose tolerance test, only decreased slightly. The clearance of C-peptide and insulin increased 100% and 60%, respectively, and the prehepatic insulin secretion was tripled during rhGH treatment; but related to the impairment in glucose tolerance, beta-cell response was still inappropriate. Our conclusion is that long-term rhGH-replacement therapy in GH deficiency adults induced a significant deterioration in glucose tolerance, profound changes in kinetics of C-peptide, and insulin and prehepatic insulin secretion, despite an increase in lean body mass and a reduction of fat mass. Therefore, rhGH treatment may precipitate diabetes in some patients already susceptible to the disorder.

Adult↗
PubMed2000

Bone mineral metabolism, bone mineral density, and body composition in patients with chronic pancreatitis and pancreatic exocrine insufficiency.

BACKGROUND: Calcium and vitamin D homeostasis seem to be abnormal in patients with exocrine pancreatic dysfunction resulting from cystic fibrosis. Only a few studies have evaluated and described bone mineral metabolism in patients with chronic pancreatitis and pancreatic insufficiency. METHODS: Thirty-two patients with chronic pancreatitis and residual exocrine pancreatic function (group 1) and 26 patients with pancreatic exocrine insufficiency (i.e., meal-stimulated intraduodenal lipase <10% of lowest normal range and steatorrhea) (group 2) were studied. Serum levels of total calcium, phosphate, 25 (OH)D, 1.25(OH)2D, alkaline phosphatase, and parathyroid hormone were measured. Bone mineral density (BMD), bone mineral content (BMC), lean body mass (LBM), and fat mass (FM) were measured using a dual-energy X-ray absorptiometry (DXA) scanner. RESULTS: Alcohol was a causative factor in 79% of the patients. Fifty-six percent in group 1 and 69% in group 2 had Z-scores of the BMD < -1. The mean Z-score was -1.16 +/- 1.29 in group 1 and -1.32 +/- 0.90 in group 2. The mean Z-score of the BMC was -1.02 +/- 1.17 vs -1.39 +/- 0.987. In both groups mean 25 (OH)D and mean 1.25(OH)2D were below reference range. Plasma concentrations of albumin-corrected calcium, alkaline phosphatase, and parathyroid hormone were in the upper range of the reference range. Mean Z-scores of LBM were -0.69 +/- 1.34 in group 1 vs -1.01 +/- 1.12 in group 2 and Z-scores of FM were -0.27 +/- 1.70 in group 1 vs -0.95 +/- 1.01 in group 2 (p <0.05). CONCLUSION: Patients with chronic pancreatitis, in particular patients with advanced disease and steatorrhea, are at risk of developing significant bone loss. Despite normal body mass index the patients are characterized by loss of lean body mass and fat mass. The present study shows that these patients have decreased serum levels of vitamin D metabolites and low bone mass.

Adult↗
PubMed1999

The effect of the deterioration of insulin sensitivity on beta-cell function in growth-hormone-deficient adults following 4-month growth hormone replacement therapy.

The purpose of the present study was to evaluate the combined effect of GH treatment on body composition and glucose metabolism, with special focus on beta-cell function in adult GHD patients. In a double-blind placebo-controlled design, 24 GHD adults (18M/6F), were randomized to 4 months treatment with biosynthetic GH 2 IU/m2s.c. daily (n =13) or placebo (n =11). At inclusion and 4 months later an oral glucose tolerance test (OGTT), a frequently sampled intravenous glucose tolerance test (FSIGT) and dual-energy X-ray absorptiometry (DXA) whole-body scanning were performed. During the study period, body weight decreased 1.6 kg from 94.0 +/- 18.7 to 92.4 +/- 19.4 kg (mean +/- SD) (P<0.05) in the GH-treated group, but remained unchanged in the placebo group. Fat mass decreased from 32.4 +/- 9.6 to 28.1 +/- 10.5 kg (P<0.001), whereas lean body mass increased from 58.3 +/- 11.5 to 61.0 +/- 11.7 kg (P<0.01) in the GH-treated group. Treatment with GH for 4 months resulted in a significant increase in fasting blood glucose (before GH 5.0 +/- 0.3 and after 5.4 +/- 0.6 mmol/l, P<0.05), fasting plasma insulin (before GH 38.4 +/- 30.2 and after 55.3 +/- 34.7 pmol/l, P<0.02) and fasting proinsulin (before 8. 1 +/- 6.7 and after 14.6 +/- 16.1 pmol/l, P<0.05). The insulin sensitivity index SI, estimated by Bergmans Minimal Model, decreased significantly [before GH 1.1 +/- 0.7 and after 0.4 +/- 0.2 10(-4)(min x pmol/l), P<0.003]. The non-insulin-dependent glucose uptake (glucose effectiveness SG did not change (before GH 0.017 +/- 0.005 and after 0.015 +/- 0.006 min-1, NS). Insulin secretion was enhanced during GH therapy, but insufficiently to match the changes in SI, resulting in a higher blood glucose level during an OGTT. Blood glucose at 120 min was 5.5 and 6.3 mmol/l before and after GH treatment, respectively (P = 0.07). One patient developed impaired glucose tolerance. Short-term GH replacement therapy in a dose of about 2 IU/m2 daily in GHD adults induces a reduction in insulin sensitivity, despite favourable changes in body composition, and an inadequate enhancement of insulin secretion.

Adenoma↗
PubMed1999

Long-term effects of growth hormone (GH) on body fluid distribution in GH deficient adults: a four months double blind placebo controlled trial.

OBJECTIVE: Short-term growth hormone (GH) treatment normalises body fluid distribution in adult GH deficient patients, but the impact of long-term treatment on body fluid homeostasis has hitherto not been thoroughly examined in placebo controlled trials. To investigate if the water retaining effect of GH persists for a longer time we examined the impact of 4 months GH treatment on extracellular volume (ECV) and plasma volume (PV) in GH deficient adults. DESIGN: Twenty-four (18 male, 6 female) adult GH deficient patients aged 25-64 years were included and received either GH (n=11) or placebo (n=13) in a double blind parallel design. METHODS: Before and at the end of each 4 month period ECV and PV were assessed directly using 82Br- and 125I-albumin respectively, and blood samples were obtained. RESULTS: During GH treatment ECV increased significantly (before: 20.48+/-0.99 l, 4 months: 23.77+/-1.38 l (P<0.01)), but remained unchanged during placebo administration (before: 16.92+/-1.01 l, 4 months: 17.60+/-1.24 l (P=0.37)). The difference between the groups was significant (P<0.05). GH treatment also increased PV (before: 3.39+/-0.27 l. 4 months: 3.71+/-0.261 (P=0.01)), although an insignificant increase in the placebo treated patients (before: 2.81+/-0.18 l, 4 months: 2.89+/-0.20 l (P=0.37)) resulted in an insignificant treatment effect (P=0.07). Serum insulin-like growth factor-I increased significantly during GH treatment and was not affected by placebo treatment. Plasma renin (mIU/l) increased during GH administration (before: 14.73+/-2.16, 4 months: 26.00+/-6.22 (P=0.03)) and remained unchanged following placebo (before: 20.77+/-5.13, 4 months: 20.69+/-6.67 (P=0.99)) leaving no significant treatment effect (P=0.08). CONCLUSION: The long-term impact of GH treatment on body fluid distribution in adult GH deficient patients involves expansion of ECV and probably also PV. These data substantiate the role of GH as a regulator of fluid homeostasis in adult GH deficiency.

Adult↗
PubMed1998

Counterregulatory hormones in insulin-treated diabetic patients admitted to an accident and emergency department with hypoglycaemia.

The aim of the study was (1) to describe hormone responses in insulin-induced hypoglycaemia and (2) to investigate if a combined treatment with intravenous glucose and intramuscular glucagon (group A) would improve glucose recovery as compared to treatment with intravenous glucose alone (group B). Eighteen adult patients with insulin-treated diabetes mellitus admitted to the Accident and Emergency Department with hypoglycaemia (plasma glucose 1.23 +/- 0.15 mmol l(-1) on admission) were randomized to one of the above treatments and plasma glucose and counterregulatory hormones were measured before and 30-120 min after treatment. Pre-treatment counterregulatory hormone concentrations were significantly lower than hormone concentrations during induced hypoglycaemia in healthy control subjects but significantly higher than healthy fasting concentrations for plasma adrenaline (p = 0.020), glucagon (p = 0.008), growth hormone (p = 0.011), and cortisol (p<0.00001). Thus, although glucagon and adrenaline responses may be absent when studying Type 1 diabetic patients in the experimental setting, both hormones increase to a significant extent in 'real-life' hypoglycaemia in this patient group, although to a lesser degree than might be expected. Plasma glucose did not differ significantly between the two treatments at any time point. Despite access to food, one of four patients in group B and one of five patients in group A had plasma glucose below 4.0 mmol l(-1) after 120 min. In conclusion, low yet significantly elevated concentrations of adrenaline and glucagon were found in diabetic patients admitted with severe hypoglycaemia to an Accident and Emergency Department.

Adult↗
PubMed1998

Long-term administration of theophylline and glucose recovery after hypoglycaemia in patients with type 1 diabetes mellitus.

The methylxanthine theophylline increases intrahepatic c-AMP and c-AMP mediates the hepatic glucose response to adrenaline and glucagon. Intravenous theophylline increases glucose recovery during acute insulin-induced hypoglycaemia and caffeine increases hypoglycaemia awareness and glucoregulatory hormone secretion. In this study we tested the hypothesis that long-term administration of theophylline might augment glucose recovery after insulin-induced hypoglycaemia. Eleven healthy subjects and 8 patients with Type 1 diabetes mellitus were made hypoglycaemic by 60 min insulin infusion (40 mU m(-2)) after 2 weeks' oral therapy with Euphyllin Retard (theophylline) or placebo. Plasma glucose nadir was 2.54 (2.31-2.77) mmol l(-1) after Euphyllin Retard and 2.27 (2.05-2.48) mmol l(-1) after placebo (mean difference 0.26 (0.05-0.58) mmol l(-1), p = 0.09) for healthy control subjects and 2.56 (2.07-3.04) mmol l(-1) and 2.19 (1.37-2.65) mmol l(-1) (mean difference 0.38 (0.12-0.63) mmol l(-1), p = 0.01), respectively, for diabetic patients. The area under the glucose curve was greater after theophylline treatment for healthy control subjects (p = 0.0292) and for diabetic patients (p = 0.0241) but there were no concomitant significant increases in plasma c-AMP or in endogenous glucose production rate. Whether the increase in glucose recovery is large enough to suggest that chronic theophylline administration will protect against insulin-induced hypoglycaemia remains unsettled.

Adult↗
PubMed1997

Body composition analysis by DEXA by using dynamically changing samarium filtration.

Dual-energy X-ray absorptiometry (DEXA) has a high accuracy for body composition analysis but is influenced by beam hardening and other error sources in the extremes of measurement. To compensate for beam hardening, the Norland XR-36 introduces a dynamically changing samarium filtration system, which depends on the current-absorber thickness. With this system we found a good agreement (r = 0.99) between reference and measured amounts of tissue or fat percentages in a plastic phantom and in smaller (approximately 0.5-4 kg) and larger (approximately 5-20 kg) piles of tissue (ox muscle and lard). Scans of six healthy volunteers covered with combinations of beef and lard (approximately 5-15 kg) showed a good agreement (r = 0.99) between reference and DEXA values of added soft tissue mass and fat percentage. We conclude that the DEXA method (and, in particular, the Norland XR-36 using dynamic filtration) has a high accuracy for body composition analysis. It has a potential for gaining status as a reference method in the future and may presently be used as a supplement to the traditional methods for body composition analysis.

Absorptiometry, Photon↗
PubMed1997

Adult growth hormone (GH)-deficient patients demonstrate heterogeneity between childhood onset and adult onset before and during human GH treatment. Adult Growth Hormone Deficiency Study Group.

The onset of adult GH deficiency may be during either adulthood (AO) or childhood (CO), but potential differences have not previously been examined. In this study the baseline and GH therapy (12.5 micrograms/kg per day) data from CO (n = 74; mean age 29 yr) and AO (n = 99; mean age 44 yr) GH-deficient adult patients have been compared. The first 6 months comprised randomized, double-blind treatment with GH or placebo, then all patients were GH-treated for a further 12 months. At baseline the height, body weight, body mass index, lean body mass, and waist/hip ratio of AO patients were significantly (P < 0.001) greater than in CO patients. Serum insulin-like growth factor-I (IGF-I) levels were below normal but were lower in CO than AO patients (P < 0.001), and the correlation with IGF binding protein-3 was stronger in CO than in AO patients. Osteocalcin concentration in CO patients was above the normal range and significantly greater than in AO patients. Both groups had significant psychosocial distress, but the deviation from normality was greater in AO patients. Throughout GH therapy there was a significant increase in lean body mass and significant decrease in percent body fat and sum of skinfolds in each group. Wais/hip ratio was decreased by long-term therapy in AO but not CO patients. Total and low density lipoprotein cholesterol levels were decreased from baseline at 6 months in AO but not CO patients and high density lipoprotein cholesterol was increased in both groups throughout therapy. IGF-I and IGF binding protein-3 were increased into the normal range by GH therapy in both groups. Mean osteocalcin level in AO patients was increased at 6 months with no further change with GH therapy, whereas in CO patients there was a steep increase up to 12 months but then a sharp decrease. Nottingham Health Profile scores showed significant improvements in physical mobility and energy at 18 months of therapy in AO patients but no consistent effects in CO patients. GH-induced side effects were mainly reported by AO patients; very few CO patients reported treatment-emergent adverse events. These results demonstrate significant differences in clinical and biochemical presentation and responses to therapy of the adult GH deficiency syndrome. This is consistent with the existence of two entities, developmental (CO) and metabolic (AO), and the different functions of GH at different periods of life.

Adult↗
PubMed1997

Basal serum pancreatic polypeptide is dependent on age and gender in an adult population.

This study is the first epidemiologically based study of basal levels of serum pancreatic polypeptide (s-PP). The basal level of serum PP has become a field of interest mainly due to the role of PP as an endocrine tumour marker, and as a marker of pancreatic neuroendocrine function after pancreas transplantation and in the case of diabetic autonomic neuropathy. The study population consisted of primarily Caucasian adults representative of a general population living around Copenhagen. Serum pancreatic polypeptide was measured in random serum samples from fasting persons (n = 623), aged 25-64 y, using a monospecific radioimmunoassay. Fasting serum pancreatic polypeptide depended on age and gender. The results demonstrated that fasting pancreatic polypeptide levels increase exponentially with age. Fitted separately for each sex, basal serum pancreatic polypeptide was found to increase by approximately 3% per year of age. Males had higher concentrations of pancreatic polypeptide in serum compared to age-matched females. Normal range and 95% reference intervals are given. The lower limit for the reference interval of the normal range was close to detection limit. We conclude that discrepancies among earlier reports on the fasting levels of serum pancreatic polypeptide are most likely due to lack of adjustment for age and gender. Thus, variation due to age and gender should be considered in evaluating fasting levels of serum pancreatic polypeptide. Whether similar considerations are important when evaluating stimulated serum pancreatic polypeptide levels remains to be elucidated.

Adult↗
PubMed1996

No effect of beta-adrenergic blockade on hypoglycaemic effect of glucagon-like peptide-1 (GLP-1) in normal subjects.

GLP-1 administration decreases blood glucose levels in normal subjects and non-insulin-dependent diabetes mellitus patients and is therefore proposed as a treatment for diabetic hyperglycaemia. The glucose lowering effect of GLP-1 is glucose dependent and therefore self-limiting, but it is not known to which extent counterregulatory mechanisms participate in this. GLP-1 was infused i.v. into 8 healthy subjects after an overnight fast at a rate of 100 pmol kg-1 h-1 for 1 h with and without beta-adrenoceptor blockade (i.v. bolus of 5 mg propranolol followed by a continuous infusion of 0.08 mg min-1). In a control experiment, saline and propranolol were infused. Hepatic glucose production was measured and blood was analysed for plasma glucose, insulin, glucagon, catecholamines, and radioactivity. Plasma GLP-1 levels were similar on the two GLP-1 infusion days and resulted in: (1) a significant decrease in plasma glucose from 5.2 +/- 0.2 to 4.1 +/- 0.1 mmol l-1 with GLP-1/propranolol infusion, and from 5.2 +/- 0.1 to 4.0 +/- 0.1 mmol l-1 with GLP-1/saline infusion (NS); (2) a corresponding significant increase in plasma insulin from 58.0 +/- 6.3 to 144.5 +/- 22.3 pmol l-1 and from 61.7 +/- 6.4 to 148.2 +/- 34.0 pmol l-1, respectively (NS); (3) a significant decrease in plasma glucagon from 11.7 +/- 1.6 to 6.5 +/- 1.5 pmol l-1 and from 10.4 +/- 1.6 to 4.6 +/- 1.0 pmol l-1, respectively; (4) a significant decrease in the rate of glucose appearance which was not significantly different on the two GLP-1 infusion days; and (5) an increase in catecholamine levels in the GLP-1/saline experiment and also in the beta-blockade experiments. We conclude that adrenergic counterregulation plays an insignificant role in curtailing GLP-1's glucose lowering effect.

Adrenergic beta-Antagonists↗
PubMed1996

Cardiovascular, metabolic, and hormonal responses to noradrenaline in diabetic patients with autonomic neuropathy.

Denervation hypersensitivity is a well-known phenomenon in patients with autonomic failure. In diabetic autonomic neuropathy hypersensitivity to beta-adrenergic stimulation has been demonstrated. We infused noradrenaline, mainly an alpha-adrenoceptor agonist, in three escalating doses (0.5, 2.5, and 5 micrograms min-1) in three age and sex matched groups of eight subjects: healthy volunteers, diabetic patients with and without autonomic neuropathy. During steady state in each infusion period we measured heart rate, blood pressure, cardiac output, hepato-splanchnic blood flow, vascular resistance, glucose kinetics, metabolites (beta-hydroxybuturate, glycerol, and lactate), and glucoregulatory hormones (noradrenaline, adrenaline, growth hormone, pancreatic polypeptide, cortisol, and insulin). Systolic and mean blood pressure increased in all groups but diabetic patients with autonomic neuropathy showed a significantly higher increase (p < 0.01) than the other two groups, with a lower threshold for increase in blood pressure. Cardiac output, hepato-splanchnic blood flow, vascular resistance, and heart rate did not change in any of the groups. The incremental increase in glucose and beta-hydroxybuturate was higher in patients with autonomic neuropathy. Otherwise, only minor changes were seen in hormonal and metabolic parameters. The cardiovascular hypersensitivity seen in diabetic autonomic neuropathy was mainly explained by increased peripheral vascular resistance, which increased significantly (p < 0.05) more in these patients. In conclusion, diabetic patients with autonomic neuropathy show denervation hypersensitivity to alpha-adrenergic stimulation by noradrenaline, especially as regards cardiovascular effects.

3-Hydroxybutyric Acid↗