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A F H Pfeiffer

Publications and source records attributed to A F H Pfeiffer.

At least 19 recordsLinked to original sources
PubMed2006

Adiponectin oligomers in human serum during acute and chronic exercise: relation to lipid metabolism and insulin sensitivity.

Beneficial effects of physical exercise include improved insulin sensitivity, which may be affected by a modulated release of adiponectin, which is exclusively synthesized in white adipose tissue and mediates insulin sensitivity. Adiponectin circulates in three different oligomers, which also have a distinct biological function. We therefore aimed to investigate the distribution of adiponectin oligomers in human serum in relation to physical activity. Thirty-eight lean and healthy individuals were investigated. Seven healthy women and 8 healthy men volunteered to investigate the effect of chronic exercise, at 3 different time points with different training intensities. These individuals were all highly trained and were compared to a control group with low physical activity (n = 15). For studying acute exercise effects, 8 healthy men participated in a bicycle test. Adiponectin was determined by ELISA, oligomers were detected by non-denaturating western blot. Total adiponectin and oligomers were unchanged by acute exercise. LDL cholesterol was significantly lower in the chronic exercise group (p = 0.03). Total adiponectin levels and oligomers were not different between these two groups and were unaltered by different training intensities. However, total adiponectin and specifically HMW oligomers correlated with HDL cholesterol (r = 0.459; p = 0.009). We conclude that acute and chronic exercise does not directly affect circulating adiponectin or oligomer distribution in lean and healthy individuals. Whether such regulation is relevant in individuals with a metabolic disorder remains to be determined. However, our data suggest that adiponectin oligomers have distinct physiological functions IN VIVO, and specifically HMW adiponectin is closely correlated with HDL cholesterol.

Adiponectin↗
PubMed2006

Effect of human body weight changes on circulating levels of peptide YY and peptide YY3-36.

BACKGROUND: Recent findings suggest that low plasma peptide YY (PYY) levels may contribute to diet-induced human obesity and justify PYY replacement therapy. Although the pharmacological value of PYY is controversial, further study of the secretion of the precursor PYY(1-36) and the pharmacologically active PYY(3-36) is indicated to determine the potential role in energy balance regulation. AIM: Our objective was to determine the effects of acute and chronic changes in human body weight on circulating levels of the putative satiety hormone peptide YY. DESIGN: Total plasma PYY levels (PYY(1-36) + PYY(3-36)) were measured in 66 lean, 18 anorectic, 63 obese, and 16 morbidly obese humans. In addition, total PYY was measured in 17 of the obese patients after weight loss and in the 18 anorectic patients after weight gain. Fasting PYY(3-36) levels were measured in 17 lean and 15 obese individuals. RESULTS: Fasting total plasma PYY levels were highest in patients with anorexia nervosa (80.9 +/- 12.9 pg/ml, P < 0.05) compared with lean (52.4 +/- 4.6 pg/ml), obese (43.9 +/- 3.8 pg/ml), or morbidly obese (45.6 +/- 11.2 pg/ml) subjects. In obese patients, weight loss of 5.4% was associated with a 30% decrease in fasting total PYY plasma levels. In anorectic patients, weight gain had no effect on fasting PYY. PYY(3-36) levels did not differ between lean (96.2 +/- 8.6 pg/ml) and obese (91.5 +/- 6.9 pg/ml) subjects. CONCLUSION: Our findings do not support a role for abnormal circulating PYY in human obesity. We conclude that circulating PYY levels in humans are significantly elevated in anorexia nervosa and, given the controversially discussed anorectic effect of PYY, could theoretically contribute to that syndrome.

Adult↗
PubMed2006

Predicting impaired glucose metabolism in women with polycystic ovary syndrome by decision tree modelling.

AIMS/HYPOTHESIS: Polycystic ovary syndrome (PCOS) is a risk factor of type 2 diabetes. Screening for impaired glucose metabolism (IGM) with an OGTT has been recommended, but this is relatively time-consuming and inconvenient. Thus, a strategy that could minimise the need for an OGTT would be beneficial. MATERIALS AND METHODS: Consecutive PCOS patients (n=118) with fasting glucose <6.1 mmol/l were included in the study. Parameters derived from medical history, clinical examination and fasting blood samples were assessed by decision tree modelling for their ability to discriminate women with IGM (2-h OGTT value >/=7.8 mmol/l) from those with NGT. RESULTS: According to the OGTT results, 93 PCOS women had NGT and 25 had IGM. The best decision tree consisted of HOMA-IR, the proinsulin:insulin ratio, proinsulin, 17-OH progesterone and the ratio of luteinising hormone:follicle-stimulating hormone. This tree identified 69 women with NGT. The remaining 49 women included all women with IGM (100% sensitivity, 74% specificity to detect IGM). Pruning this tree to three levels still identified 53 women with NGT (100% sensitivity, 57% specificity to detect IGM). Restricting the data matrix used for tree modelling to medical history and clinical parameters produced a tree using BMI, waist circumference and WHR. Pruning this tree to two levels separated 27 women with NGT (100% sensitivity, 29% specificity to detect IGM). The validity of both trees was tested by a leave-10%-out cross-validation. CONCLUSIONS/INTERPRETATION: Decision trees are useful tools for separating PCOS women with NGT from those with IGM. They can be used for stratifying the metabolic screening of PCOS women, whereby the number of OGTTs can be markedly reduced.

Adult↗
PubMed2006

Glucagon suppression of ghrelin secretion is exerted at hypothalamus-pituitary level.

CONTEXT: The mechanisms underlying the well-known glucagon-induced satiety effect are unclear. Recently, we showed that glucagon induces a remarkable decrease in the orexigenic hormone ghrelin that might be responsible for this effect. OBJECTIVE: The objective of this study was to evaluate the putative role of the hypothalamic pituitary axis in glucagon's suppressive effect on ghrelin secretion. DESIGN, SUBJECTS, AND METHODS: Prospectively, we studied the endocrine and metabolic responses to im glucagon administration in 22 patients (16 males; age, 21-68 yr; body mass index, 28.1 +/- 1.1 kg/m(2)) with a known hypothalamic-pituitary lesion and at least one pituitary hormone deficiency. Control experiments were performed in 27 healthy subjects (15 males; age, 19-65 yr; body mass index, 25.5 +/- 0.9 kg/m(2)). RESULTS: The suppression of ghrelin by glucagon measured as area under the curve(240 min) was significantly greater in controls when compared with patients (P < 0.01). Although there was a significant decrease in ghrelin in controls (P < 0.001), ghrelin was almost unchanged in patients (P = 0.359). Changes in glucagon, glucose, and insulin levels were comparable between both groups. CONCLUSIONS: We show that the hypothalamic-pituitary axis plays an essential role in the suppression of ghrelin induced by im glucagon administration. Glucagon significantly decreases ghrelin levels in healthy subjects. However, in the absence of an intact hypothalamic-pituitary axis, this effect was abolished. The mechanisms responsible for our observation are unlikely to include changes in glucose or insulin levels.

Adult↗
PubMed2006

Signalling mechanisms linking hepatic glucose and lipid metabolism.

Fatty liver and hepatic triglyceride accumulation are strongly associated with obesity, insulin resistance and type 2 diabetes, and are subject to nutritional influences. Hepatic regulation of glucose and lipid homeostasis is influenced by a complex system of hormones, hormonally regulated signalling pathways and transcription factors. Recently, considerable progress has been made in elucidating molecular pathways and potential factors that are affected in insulin-resistant states. In this review we discuss some of the key factors that are involved in both the regulation of glucose and lipid metabolism in the liver. Understanding the molecular network that links hepatic lipid accumulation and impaired glucose metabolism may provide targets for dietary or pharmacological interventions.

Animals↗
PubMed2006

Free fatty acids increase androgen precursors in vivo.

CONTEXT: There is considerable evidence that metabolic factors such as insulin resistance may induce hyperandrogenemia in polycystic ovary syndrome. However, other metabolic factors such as free fatty acids (FFAs) may also contribute to androgen excess. OBJECTIVE: The objective was to study effects of FFAs on adrenal production of androgen precursors in vivo. DESIGN AND PARTICIPANTS: We investigated eight healthy young men, because male individuals produce the androgen precursors dehydroepiandrosterone (DHEA), DHEA sulfate, and androstenedione predominantly in the adrenal gland. A randomized controlled crossover trial was performed. INTERVENTION: After a 10-h overnight fast, 20% lipid/heparin or saline/heparin infusion was given at a rate of 1.5 ml/min. Four hours after start of lipid infusion, a euglycemic hyperinsulinemic clamp was performed. MAIN OUTCOME MEASURES: DHEA, androstenedione, 17-OH-progesterone, testosterone, estrone, LH, FSH, ACTH, and cortisol were measured. RESULTS: The adrenal androgen precursors DHEA and androstenedione showed a circadian decline during saline/heparin infusion (P < 0.05 vs. baseline, respectively), whereas no significant changes were observed during lipid/heparin infusion (P = not significant vs. baseline, respectively). Correspondingly, DHEA and androstenedione values were significantly elevated during lipid compared with saline infusion (P < 0.05, respectively), and areas under curve of both androgen precursors were significantly increased with lipid compared with saline infusion. Notably, all changes were detected before induction of insulin resistance. CONCLUSIONS: This study demonstrates that FFAs increase production of androgen precursors in vivo in men. These data tentatively suggest that hyperandrogenemia in polycystic ovary syndrome may be induced, at least in part, by elevated FFAs.

17-alpha-Hydroxyprogesterone↗
PubMed2006

Increase in adiponectin levels during pioglitazone therapy in relation to glucose control, insulin resistance as well as ghrelin and resistin levels.

Glitazones increase the secretion of the adipocyte-derived hormone adiponectin. Furthermore, the gastric signal peptide ghrelin is known to suppress adiponectin expression in adipocyte cell culture models. It is not known whether the increase in adiponectin during glitazone therapy is due to a suppression of ghrelin levels, a decrease of resistin concentrations or an amelioration of glucose control. In 10 patients (age 71+/-9 yr, body mass index 29.9+/-3.6 kg/m(2), HbA1c 6.9+/-0.5%) with Type 2 diabetes, who had already been treated with sulfonylureas, we additionally initiated a pioglitazone therapy (30 mg/day) for 12 weeks. To investigate the pioglitazone effect independently of blood glucose, glycosylated hemoglobin (HbA1c) was kept unchanged by reducing the daily dose of sulfonylurea if necessary. Ghrelin concentration [radioimmunoassay (RIA), Phoenix Pharmaceuticals, Mountain View, CA, USA], adiponectin levels [enzyme-linked immunosorbent assay (ELISA), Biovendor, Heidelberg, Germany] as well as resistin concentrations (ELISA, Linco Research, St. Charles, MO, USA) were measured before and after pioglitazone. Glucose control remained unchanged within the 12-week pioglitazone therapy (HbA1c 6.9+/-0.5% before vs 6.8+/-0.6% after pioglitazone) while body weight increased from 86.6+/-9.2 to 88.0+/-9.4 kg (p<0.05), and insulin concentration decreased from 19.6+/-5.7 to 10.1+/-1.6 microU/ml (p<0.05). Adiponectin concentration increased in all patients from 7.70+/-2.47 to 23.33+/-8.28 microg/ml (p<0.01), while resistin concentrations tended to decrease (by 15%; p=0.059). However, ghrelin remained unchanged during therapy. No correlations were observed either between ghrelin, resistin, insulin and adiponectin, or between body weight and hormone plasma levels. The increase in adiponectin levels during pioglitazone therapy seems to be at least partly independent of blood glucose and insulin concentration as well as of ghrelin levels, and it was not associated with a decrease in resistin concentrations.

Adiponectin↗
PubMed2006

Serum resistin increases in a postprandial state during liquid meal challenge test in healthy human subjects.

The role of resistin in humans is controversial although resistin has been linked to atherosclerotic and inflammatory processes. In rodents, resistin expression is suppressed after food restriction while central administration of resistin promotes short-term satiety. However, the nature of postprandial responses in circulating resistin in humans is unknown. Therefore, we investigated postprandial resistin concentrations in a pilot study in 19 healthy subjects and 19 controls matched for age and body mass index (BMI). Serum resistin, insulin and non-esterified fatty acids (NEFA) concentrations as well as plasma glucose and triglycerides were repeatedly assessed before and after ingestion of an isocaloric standardized liquid meal during a 300 min period.After consumption of liquid meal, serum resistin levels increased compared to fasting control (p=0.037). Postprandial plasma glucose and serum insulin increased (p<0.001) with lower glucose responses in females (p=0.001) and lower insulin responses in males (p=0.012). Plasma triglycerides increased and serum NEFA decreased with similar gender responses (p=0.025 and p<0.001, respectively). Serum resistin was not correlated to glucose, insulin, triglyceride, and NEFA responses to liquid meal challenge tests. The present data suggest that serum resistin increases postprandially in healthy humans. Additional studies are needed to elucidate normal 24-h daytime profiles in humans and differential response of serum resistin to macronutrient composition of meals.

Adult↗
PubMed2005

Impact of cereal fibre on glucose-regulating factors.

AIMS/HYPOTHESIS: Insoluble dietary fibre intake is associated, by unknown mechanisms, with a reduced risk of type 2 diabetes. We investigated whether a short-term dietary intervention with purified insoluble fibres influences acute and delayed responses of glucose, insulin, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1. METHODS: Fourteen healthy women with NGT were studied for 300 min on six to eight occasions. Subjects consumed three matched portions of control (C) or fibre-enriched bread (10.4-10.6 g/portion; wheat fibre [WF], oat fibre [OF], and, in a substudy [n=9], resistant starch [RS]) followed by control (C-C, C-WF, C-OF, C-RS) on subsequent days. RESULTS: Fibre enrichment accelerated the early insulin response (fibrextime interaction p=0.026 for WF, p<0.001 for OF, p=0.126 for RS; time of maximal concentration [T(max)], C 57.9+/-5.9, WF 49.3+/-2.5 [p=0.086], OF 46.1+/-2.9 [p=0.026], RS 46.7+/-5.8 min [p=0.029]). It was also associated with an earlier postprandial GIP response after OF (T(max), C 83.6+/-7.2, WF 70.7+/-6.0 [p=0.054], OF 64.3+/-6.9 [p=0.022], RS 60.0+/-5.0 [p>0.15]). Increased fibre intake for 24 h was further associated with a reduced postprandial glucose response on the following day subsequent to ingestion of a control meal (AUC(C-C) 4,140+/-401, AUC(C-WF) 2,850+/-331 [p=0.007], AUC(C-OF) 2,830+/-277 [p=0.011]), with no difference in maximal concentration and T(max) of glucose responses. No differences in insulin responses were observed 24 h after the fibre-enriched diets compared with control (p>0.15). Colonic fermentation was increased only on study days C-OF (p=0.017) and C-RS (p=0.016). CONCLUSIONS/INTERPRETATION: The consumption of highly purified insoluble dietary fibres accelerated the acute GIP and insulin response and was further associated with enhanced postprandial carbohydrate handling the following day upon ingestion of a control meal.

Adult↗
PubMed2005

A dietary pattern protective against type 2 diabetes in the European Prospective Investigation into Cancer and Nutrition (EPIC)--Potsdam Study cohort.

AIMS/HYPOTHESIS: The aim of this study was to identify a dietary pattern associated with diabetes-related biomarkers and to investigate whether this pattern is associated with the incidence of type 2 diabetes. METHODS: A nested case-control study of 192 cases of incident type 2 diabetes and 382 control subjects matched for sex and age was conducted. All subjects were participants in the population-based European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study. Dietary pattern score was derived using intake data on 48 food groups as exposure variables and the biomarkers HbA1c, HDL cholesterol, C-reactive protein and adiponectin as response variables in reduced rank regression. The association of the score with diabetes risk was estimated by conditional logistic regression analysis. RESULTS: A high score for the identified dietary pattern was characterised by a high intake of fresh fruit and a low intake of high-caloric soft drinks, beer, red meat, poultry, processed meat, legumes and bread (excluding wholegrain bread). Subjects with high scores had high plasma concentrations of HDL cholesterol and adiponectin and low plasma concentrations of HbA1c and C-reactive protein. After multivariate adjustment, the odds ratios for type 2 diabetes across increasing quintiles of the dietary pattern score were 1.0, 0.59, 0.51, 0.26 and 0.27, respectively (p = 0.0006 for trend). CONCLUSIONS/INTERPRETATION: A high score for the identified dietary pattern is associated with a more favourable biomarker profile and a substantially reduced incidence of type 2 diabetes.

Adiponectin↗
PubMed2005

[Preventing type 2 diabetes: what does dietary fiber achieve?].

On the basis of the currently available data, an increase in the uptake of indigestible roughage can be recommended as a means of reducing the risk of developing type 2 diabetes and cardiovascular diseases. In concert with other factors of a healthy lifestyle--including physical exercise, abstention from nicotine, the consumption of only moderate amounts of alcohol, reducing the intake of saturated fats, and--the main factor--ensuring that overweight does not develop, this dietary modification would appear to be an effective measure for avoiding most cases of type 2 diabetes.

Adult↗
PubMed2005

Ghrelin is not suppressed in hyperglycemic clamps by gastric inhibitory polypeptide and arginine.

UNLABELLED: Systemic ghrelin concentration falls rapidly after nutrient ingestion in vivo. The effect incretins on ghrelin secretion in humans remains unclear. We quantified circulating ghrelin concentrations under hyperglycemic conditions combined with infusion of gastric inhibitory polypeptide (GIP) and arginine. METHODS: Eight healthy volunteers were studied with a hyperglycemic clamp followed by addition of GIP (2 pmol.kg(-1).min(-1), 60-115 min) and an arginine-bolus and -infusion (10 mg.kg(-1).min(-1), 90-115 min). RESULTS: Hyperglycemia alone increased circulating insulin concentrations (p<0.01), and decreased ghrelin concentrations to 89.8% of basal (p=0.208). GIP-infusion resulted in circulating insulin concentration of 1109+/-942 pmol/l (p<0.02) and no further decrease of ghrelin (86.2% of baseline, p=0.050). Under arginine- and GIP-infusion together, insulin concentrations increased progressively to 3005+/-1604 pmol/l (p<0.01) without further decreasing in ghrelin concentrations (98.9% of baseline, p=0.575). CONCLUSIONS: Hyperglycemic hyperinsulinemia and further increases of hyperinsulinemia to supraphysiological and high supraphysiological concentrations under GIP- and arginine-infusion do not significantly decrease ghrelin concentrations in healthy subjects. Moreover, there is no dose-dependent suppression of ghrelin by insulin in the hyperglycemic condition. Neither GIP nor arginine affected ghrelin release.

Adult↗
PubMed2005

Effects of marked weight loss on plasma levels of adiponectin, markers of chronic subclinical inflammation and insulin resistance in morbidly obese women.

OBJECTIVE: Obesity is linked to the insulin resistance syndrome (IRS), type 2 diabetes (T2D) and cardiovascular disease. Markers of chronic subclinical inflammation such as high-sensitive C-reactive protein (hs-CRP) and interleukin 6 (IL-6) are closely related to insulin resistance and obesity. Recent evidence suggests that adiponectin, a protein whose circulating levels are decreased in obesity, has anti-inflammatory properties, and also appears to enhance potently insulin action and therefore appears to function as a signal produced by adipose tissue that influences whole-body glucose metabolism. SUBJECTS AND METHODS: We investigated the cross-sectional and longitudinal association of adiponectin with CRP and IL-6 in 41 morbidly obese women with different stages of glucose tolerance before and 17 months after significant weight loss induced by gastric surgery. Adiponectin was measured by RIA. CRP and IL-6 were determined by commercially available ELISA systems. RESULTS: Weight loss induced a significant shift from T2D (preoperatively 34% vs postoperatively 2%) to impaired glucose tolerance (IGT) (37% preoperatively vs 30% postoperatively) and normal glucose tolerance (NGT) (29% preoperatively vs 68% postoperatively). Preoperatively adiponectin levels were negatively correlated with CRP (r=-0.59, P<0.0006), IL-6 (r=-0.42, P<0.02) and leukocytes (r=-0.41, P<0.007). After gastroplasty, adiponectin concentrations increased significantly (15.4+/-8.2 vs 19.8+/-6.2 microg/ml, P<0.005) associated with changes of weight and body mass index (r=-0.45, P<0.007; r=-0.35, P<0.04). Furthermore, preoperative CRP was significantly associated with changes in adiponectin even after adjustment for sex, age, preoperative body mass index (BMI) impaired glucose metabolism and changes in BMI and changes in BMI (standardized beta 0.61, P=0.005). CONCLUSION: Levels of adiponectin, which are associated with markers of chronic subclinical inflammation, could be significantly increased after weight loss in morbidly obese patients. This increase was more pronounced in patients with NGT compared to those with T2D and IGT. Preoperative levels of CRP are predictive for changes of adiponectin after weight loss.

Adiponectin↗
PubMed2005

Arabinoxylan-enriched meal increases serum ghrelin levels in healthy humans.

Soluble fibre like arabinoxylan (AX) is thought to have beneficial effects on metabolism. In this study, we investigated the effect of a breakfast enriched in AX fibre on glucose, insulin and ghrelin values. AX-enriched and control breakfasts were served to fifteen young volunteers (nine female, six male). Glucose, insulin and ghrelin responses were measured after the meal. To avoid effects from differences in glucose metabolism, further analysis was restricted to those subjects with known normal glucose regulation (seven female, four male). The AX fibre-enriched breakfast did not significantly change glucose levels for two hours after breakfast, but decreased insulin levels in the entire cohort (p = 0.035). Glucose response was also not significantly different in subjects with normal glucose regulation (p = 0.367), and the insulin responses after an AX-enriched breakfast showed only a tendency towards lower values (p = 0.065). Nevertheless, plasma ghrelin two hours after AX-enriched breakfast was higher than after the control meal (396.1 +/- 36.4 pg/ml vs. 328.3 +/- 32.6 pg/ml, p < 0.001). In subjects with normal glucose regulation, the AX-enriched breakfast increased ghrelin levels without any significant difference in glucose or insulin response. This effect is therefore unlikely to be mediated by insulin, but the underlying mechanism remains to be elucidated.

Adult↗
PubMed2005

In vivo activity of 11beta-hydroxysteroid dehydrogenase type 1 and free fatty acid-induced insulin resistance.

INTRODUCTION: Free fatty acids (FFAs) induce hepatic insulin resistance and enhance hepatic gluconeogenesis. Glucocorticoids (GCs) also stimulate hepatic gluconeogenesis. The aim of this study was to investigate whether the FFA-induced hepatic insulin resistance is mediated by increased activity of hepatic 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1), accompanied by elevated hepatic cortisol levels. METHODS: Following a 10-h overnight fast, six healthy male volunteers were investigated. A euglycaemic hyperinsulinaemic clamp was performed during lipid or saline infusion. To assess hepatic 11beta-HSD1 activity, plasma cortisol levels were measured after oral administration of cortisone acetate during lipid or saline infusion. In addition, 11beta-HSD activities were determined in vivo by calculating the urinary ratios of GC metabolites. RESULTS: Lipid infusion increased FFAs (5.41 +/- 1.00 vs. 0.48 +/- 0.20 mmol/l; P < 0.005) and significantly increased insulin resistance [glucose infusion rate (GIR) 6.02 +/- 2.60 vs. 4.08 +/- 2.15 mg/kg/min; P < 0.005]. After lipid and saline infusions no changes in 11beta-HSD1 activity were found, neither by changes in cortisone acetate to cortisol conversion nor by differences in urinary free cortisol (UFF) or cortisone (UFE), 5beta-tetrahydrocortisol (THF), 5alpha-THF, cortisone (THE), UFF/UFE and (5alpha-THF + THF)/THE ratios. CONCLUSIONS: We found no change in hepatic and whole-body 11beta-HSD1 activity during acute FFA-induced insulin resistance. Further studies are necessary to clarify whether 11beta-HSD1 in muscle and adipose tissue is influenced by FFAs and whether 11beta-HSD1 is involved in other conditions of insulin resistance.

11-beta-Hydroxysteroid Dehydrogenase Type 1↗