Prophylactic incisional negative pressure wound therapy reduces the risk of surgical site infection after caesarean section in obese women: a pragmatic randomised clinical trial.

OBJECTIVE: To evaluate the reduction of surgical site infections by prophylactic incisional negative pressure wound therapy compared with standard postoperative dressings in obese women giving birth by caesarean section. DESIGN: Multicentre randomised controlled trial. SETTING: Five hospitals in Denmark. POPULATION: Obese women (prepregnancy body mass index (BMI) ≥30 kg/m2 ) undergoing elective or emergency caesarean section. METHOD: The participants were randomly assigned to incisional negative pressure wound therapy or a standard dressing after caesarean section and analysed by intention-to-treat. Blinding was not possible due to the nature of the intervention. MAIN OUTCOME MEASURES: The primary outcome was surgical site infection requiring antibiotic treatment within the first 30 days after surgery. Secondary outcomes included wound exudate, dehiscence and health-related quality of life. RESULTS: Incisional negative pressure wound therapy was applied to 432 women and 444 women had a standard dressing. Demographics were similar between groups. Surgical site infection occurred in 20 (4.6%) women treated with incisional negative pressure wound therapy and in 41 (9.2%) women treated with a standard dressing (relative risk 0.50, 95% CI 0.30-0.84; number needed to treat 22; P = 0.007). The effect remained statistically significant when adjusted for BMI and other potential risk factors. Incisional negative pressure wound therapy significantly reduced wound exudate whereas no difference was found for dehiscence and quality of life between the two groups. CONCLUSION: Prophylactic use of incisional negative pressure wound therapy reduced the risk of surgical site infection in obese women giving birth by caesarean section. TWEETABLE ABSTRACT: RCT: prophylactic incisional NPWT versus standard dressings postcaesarean in 876 women significantly reduces the risk of SSI.

SorCS2 is required for BDNF-dependent plasticity in the hippocampus.

SorCS2 is a member of the Vps10p-domain receptor gene family receptors with critical roles in the control of neuronal viability and function. Several genetic studies have suggested SORCS2 to confer risk of bipolar disorder, schizophrenia and attention deficit-hyperactivity disorder. Here we report that hippocampal N-methyl-d-aspartate receptor-dependent synaptic plasticity is eliminated in SorCS2-deficient mice. This defect was traced to the ability of SorCS2 to form complexes with the neurotrophin receptor p75NTR, required for pro-brain-derived neurotrophic factor (BDNF) to induce long-term depression, and with the BDNF receptor tyrosine kinase TrkB to elicit long-term potentiation. Although the interaction with p75NTR was static, SorCS2 bound to TrkB in an activity-dependent manner to facilitate its translocation to postsynaptic densities for synaptic tagging and maintenance of synaptic potentiation. Neurons lacking SorCS2 failed to respond to BDNF by TrkB autophosphorylation, and activation of downstream signaling cascades, impacting neurite outgrowth and spine formation. Accordingly, Sorcs2-/- mice displayed impaired formation of long-term memory, increased risk taking and stimulus seeking behavior, enhanced susceptibility to stress and impaired prepulse inhibition. Our results identify SorCS2 as an indispensable coreceptor for p75NTR and TrkB in hippocampal neurons and suggest SORCS2 as the link between proBDNF/BDNF signaling and mental disorders.

Metabolic effects of lifestyle intervention in obese pregnant women. Results from the randomized controlled trial 'Lifestyle in Pregnancy' (LiP).

AIMS: The Lifestyle in Pregnancy intervention in obese pregnant women resulted in significantly lower gestational weight gain compared with the control group, but without improvement in rates of clinical pregnancy complications. The impact of the lifestyle intervention on metabolic measurements in the study participants is now reported. METHODS: The Lifestyle in Pregnancy study was a randomized controlled trial among 360 obese women (BMI 30-45 kg/m²) who were allocated in early pregnancy to lifestyle interventions with diet counselling and physical activities or to the control group. Fasting blood samples, including plasma glucose, insulin, lipid profile and capillary blood glucose during a 2-h oral glucose tolerance test were carried out three times throughout pregnancy. Insulin resistance was estimated with the homeostasis model assessment of insulin resistance. RESULTS: Three hundred and four women (84%) were followed until delivery. Women in the intervention group had a significantly lower change in insulin resistance (HOMA-IR) from randomization to 28-30 weeks' gestation compared with control subjects (mean ± SD: 0.7 ± 1.3 vs. 1.0 ± 1.3, P = 0.02). Despite a significantly lower gestational weight gain in the intervention group, there was no difference between the groups with respect to total cholesterol, HDL, LDL or triglycerides. CONCLUSIONS: Lifestyle intervention in obese pregnant women resulted in attenuation of the physiologic pregnancy-induced insulin resistance. Despite restricted gestational weight gain, there were no changes in glucose or lipid metabolism between the groups.

Pregestational body mass index is related to neonatal abdominal circumference at birth--a Danish population-based study.

OBJECTIVES: To examine the impact of maternal pregestational body mass index (BMI) and smoking on neonatal abdominal circumference (AC) and weight at birth. To define reference curves for birth AC and weight in offspring of healthy, nonsmoking, normal weight women. DESIGN: Population-based study. SETTING: Data from the Danish Medical Birth Registry. POPULATION: All live singletons without congenital malformations in Denmark 2004-10. METHODS: Data on 366,886 singletons at 35(+0) to 41(+6) weeks(+days) of gestation were extracted and analysed using multivariate linear regressions. MAIN OUTCOME MEASURES: Birth AC and weight in relation to pregestational maternal BMI, maternal smoking and medical conditions (any). RESULTS: Birth AC and weight increased with increasing pregestational BMI, and decreased with smoking (P < 0.0001). Reference curves were created for offspring of healthy, nonsmoking mothers with normal pregestational BMI. Mean AC ranged from 30.1 cm and 30.2 cm at 35 weeks of gestation to 33.9 cm and 34.1 cm at 41 weeks of gestation, for girls and boys, respectively. Mean birthweight ranged from 2581 and 2666 g at 35 weeks to 3705 and 3852 g at 41 weeks of gestation for girls and boys, respectively. Pregestational BMI correlated more to the Z score of birthweight than to the Z score of AC (P < 0.0001). CONCLUSION: Birth AC and weight are affected by maternal smoking status and pregestational BMI. Pregestational BMI correlated more to birthweight than to AC. Using data from healthy, nonsmoking mothers with normal pregestational BMI we have provided new reference curves for birth AC and birthweight.

Parity and risk of diabetes in a Danish nationwide birth cohort.

AIMS: The purpose was to elucidate the association between parity and the incidence of diabetes using national register data. METHODS: The study population consisted of all Danish women with a singleton delivery in 1982/1983 (n = 100,669), who subsequently had 74,966 deliveries. The included women were followed up via registries until the end of 2006 for subsequent deliveries, diagnosis of diabetes and death/emigration. RESULTS: A total of 2021 cases (2.0%) were diagnosed with diabetes in connection with hospitalization or outpatient treatment during follow-up. Analyses were adjusted for fetal weight and duration of gestation, both at index pregnancy. Cox regression analysis with parity as a time-varying exposure, stratified in two age groups, showed an association between parity and risk of a diagnosis of diabetes. In women <33 years of age, parity 2, 3 and 4 + were associated with an increased risk of being diagnosed with diabetes compared with parity 1 [relative risks: 1.6 (95% confidence interval 1.1-2.3), 2.8 (1.8-4.3) and 2.5 (1.3-4.8), respectively]. Among women >33 years of age, parity 2 was associated with a significantly lower risk of diabetes diagnosis compared with parity 1, whereas parity 4 + was associated with a significantly higher risk of diabetes diagnosis compared with parity 1. CONCLUSIONS: The study shows that the risk of diabetes diagnosis increases with parity in young Danish women. This may support a causal association between diabetes and parity.

Effects of glucose, glycerol, 3-hydroxybutyrate, insulin, and leptin on placental growth hormone secretion in placental explants.

Placental growth hormone (PGH) is secreted from the syncytiotrophoblast in increasing amounts during pregnancy. The physiology and regulation of PGH is not well known; however, low glucose levels appear to stimulate PGH liberation IN VITRO and IN VIVO. PGH appears to have lipolytic effects, and inverse correlations between maternal body mass index and serum PGH levels have been reported. Therefore, substances related to maternal adipose tissue metabolism could influence PGH secretion. The effect of insulin, glycerol, 3-hydroxybutyrate (3-OHB), and leptin on PGH and human placental lactogen (hPL) secretion from cultured placental explants was studied. In glucose-free media, PGH content increased upto 237.5+/-28.4% of control media (p<0.001, ANOVA). Insulin levels were without effect on PGH secretion, as were 3-OHB, leptin, and glycerol at 0.02 mmol/l. Glycerol at 0.2 mmol/l increased PGH in all of the placental explants studied (n=8; mean increase 27.3+/-7.1%), and this difference was significantly different from the control explants (p=0.004). The liberation of hPL to culture media was different from PGH and was influenced by glucose and insulin. In conclusion, the absence of glucose profoundly increased PGH secretion in cultured placental explants. Addition of glycerol in physiologically relatively high concentrations showed a less pronounced stimulatory effect.

Proposed diagnostic thresholds for gestational diabetes mellitus according to a 75-g oral glucose tolerance test. Maternal and perinatal outcomes in 3260 Danish women.

AIMS: To study if established diagnostic threshold values for gestational diabetes based on a 75-g, 2-h oral glucose tolerance test can be supported by maternal and perinatal outcomes. METHODS: Historical cohort study of 3260 pregnant women examined for gestational diabetes on the basis of risk indicators. Information on oral glucose tolerance test results and clinical outcomes were collected from medical records. RESULTS: There was an increased risk of delivering a macrosomic infant in women with 2-h capillary blood glucose of 7.8-8.9 mmol/l compared with women with 2-h glucose < 7.8 mmol/l. Despite treatment, 2-h glucose of 9.0-11.0 mmol/l and > or = 11.1 mmol/l were both associated with increased rates of macrosomia, spontaneous preterm delivery, hypertensive complications, and neonatal hypoglycaemia. Adverse outcomes tended to be more frequent in women with 2-h glucose > or = 11.1 mmol/l than in women with 2-h glucose of 9.0-11.0 mmol/l. CONCLUSIONS: The risk for several maternal and perinatal complications increased with the diagnostic threshold for 2-h glucose. Large-scale blinded studies are needed to clarify the question of a clinically meaningful diagnosis of gestational diabetes mellitus. Until these results are available, a 2-h threshold level of 9.0 mmol/l after a 75-g oral glucose tolerance test seems acceptable.

Effects of androstenedione, insulin and luteinizing hormone on steroidogenesis in human granulosa luteal cells.

BACKGROUND: The present study was conducted to investigate the effect of androstenedione, insulin and LH on human granulosa cell oestrogen and progesterone production. We postulated that elevated concentrations of androstenedione, insulin and LH may be important modulators of granulosa cell steroidogenesis. METHODS: Granulosa cells obtained in connection with IVF procedures were cultured for a total of 4 days in serum-free medium containing androstenedione (10(-6) mol/l). We tested the effect of androstenedione (10(-5) mol/l) on insulin (0-800 microIU/ml), LH (1-10 ng/ml) as well as on insulin + LH-stimulated oestrogen and progesterone production. RESULTS: Insulin increased the basal secretion of steroid hormones, and furthermore augmented LH-stimulated oestrogen and progesterone accumulation in granulosa cell cultures. Androstenedione (10(-5) mol/l) stimulated basal oestrogen production, but significantly reduced (32-58%) insulin + LH-stimulated oestrogen and progesterone secretion (P < 0.05). CONCLUSION: These results suggest that high androstenedione concentrations may act directly to impair insulin augmentation of LH-stimulated oestradiol and progesterone production in cultured human granulosa luteal cells. This is compatible with the hypothesis that high androgen levels may inhibit oestrogen production in polycystic ovary follicles, and as such may contribute to anovulation and infertility in women with polycystic ovary syndrome.

Effects of leptin on basal and FSH stimulated steroidogenesis in human granulosa luteal cells.

BACKGROUND: Body weight influences fertility and studies in mice have indicated that leptin is one of the mediators of this effect. Leptin is believed to centrally stimulate the hypothalamic-pituitary axis resulting in increased gonadotropin release. Moreover, leptin is present in follicular fluid and the receptor is expressed in the human ovary. The aim of this study was to evaluate the direct effect of leptin on cultured human granulosa cell steroidogenesis. METHODS: Granulosa cells were obtained in connection with IVF procedures, and then cultured in a serum-free medium containing androstenedione (1 microM) for a total of 4 days. After 2 days of culture the medium was changed and the hormones under study were added. We tested the effect of leptin (1, 20, 100 ng/ml) on basal, FSH (10-100 ng/ml), and FSH (10-100 ng/ml)+IGF-I (30 ng/ml) stimulated steroidogenesis. RESULTS: Leptin (20 ng/ml and 100 ng/ml) significantly reduced basal and FSH-stimulated estradiol secretion (p<0.05). Basal and FSH (10 and 30 ng/ml) stimulated progesterone production was significantly inhibited by leptin 20 ng/ml, whereas leptin 100 ng/ml significantly reduced basal but not FSH stimulated progesterone production. Finally, steroidogenesis stimulated by IGF-I alone and in combination with FSH was not influenced by leptin. CONCLUSION: These results suggest that leptin acts directly to inhibit basal and FSH stimulated estradiol and progesterone production in cultured human granulosa cells. This raises the possibility that high circulating leptin levels as seen in obese women may compromise fertility through peripheral mechanisms.

Impact of growth hormone administration on other hormonal axes.

Growth hormone regulates several other hormonal systems and vice versa. The present review focusses on the effect of GH administration in adults on selected hormonal systems. Growth hormone treatment has been linked to development of central hypothyroidism in hypopituitary children. We now know that GH enhances the extra-thyroidal conversion of T(4) to T(3). Lowering of T(4) during GH treatment therefore reflects biochemical unmasking of subclinical central hypothyroidism. In normal adults GH administration does not affect the pituitary-gonadal axis. There is, however, evidence to suggest that GH substitution in hypopituitary adults enhances peripheral actions of sex steroids (males) and stimulates gonadal function (females). Both increased, unchanged and reduced basal and ACTH stimulated glucocorticoid levels have been reported during GH treatment. Several groups have recorded reduced levels of cortisol binding globulin with unchanged free cortisol concentrations. Regular assessment of thyroid and glucocorticoid status during GH substitution in GH-deficient patients is recommended.

Synergistic effects of growth hormone and insulin-like growth factor-I on differentiation and replication of cultured human luteinized granulosa cells.

BACKGROUND: The present study was designed to assess the effects of insulin-like growth factor-I (IGF-I) alone and in combination with growth hormone (GH) on differentiation and replication in cultured human granulosa cells. METHODS: Granulosa cells from patients undergoing in vitro fertilization were isolated and cultured for 2 days in culture medium with 10% serum, the medium was removed and the cells were incubated with IGF-I (1, 10 and 100 ng/ml) with or without GH (10 ng/ml) in serum-free medium and in the presence of 3H-methylthymidine (2 microCi/ml). RESULTS: IGF-I alone resulted in a significant dose-dependent increase in medium estradiol (E2) (p<0.05) and progesterone (P) (p<0.001) and suppression of IGF-binding protein-1 (IGFBP-1) (p<0.001), without any increase in [3H]-thymidine incorporation (P=0.10). The combination of IGF-I and GH further increased the release of E2 (p<0.001), and the amount of [3H]-thymidine incorporation (p<0.001). CONCLUSION: These results indicate a synergistic effect of IGF-I and GH on differentiation and replication of human granulosa cells, and thus support a role of both GH and IGF-I in regulation of ovarian function.

Increased pulsatile, but not basal, growth hormone secretion rates and plasma insulin-like growth factor I levels during the periovulatory interval in normal women.

The secretion of GH changes during the menstrual cycle, exhibiting high levels during the periovulatory phase (PO). Previous studies have not investigated whether this difference in GH status is due to increased secretion or reduced clearance of pituitary GH and amplified pulsatile vs. basal GH secretion. It is also unclear whether the PO phase is accompanied by changes in circulating insulin-like growth factor I (IGF-I). In this study we investigated the 24-h GH release patterns in the early follicular (EF) vs. the periovulatory menstrual phase in the same individuals. Ten young (aged 24-34 yr) healthy women with regular menses were studied with deconvolution analysis of GH profiles obtained by blood sampling every 20 min for 24 h, followed by an arginine stimulation test. A high sensitivity immunofluorometric GH assay was used. All women were studied in both the EF and PO phases in random order. There were no differences in the basal GH secretion rate or GH half-life during the two phases. The number of GH secretory bursts identified during the 24-h sampling period was significantly increased during the PO (13.3 +/- 0.5) compared to the EF (10.3 +/- 0.6) phase (P = 0.002); conversely, the mean interburst interval was shorter in the PO (107 +/- 5 min) than in the EF (134 +/- 8 min) phase (P = 0.004). There was no difference in GH pulse mass (P = 0.13) or amplitude (P = 0.21) between the two phases. The pulsatile GH production rate (milligrams per L/24 h) was significantly elevated during the PO (61 +/- 6) compared to that during the EF (37 +/- 8; P = 0.004). Increased total GH pulse area was confirmed by Cluster analysis (P = 0.027). Furthermore, the 24-h mean serum GH concentration was significantly increased in the PO (1.4 +/- 0.1 mg/L) vs. that in the EF (0.9 +/- 0.1 mg/L; P = 0.002). There was a positive correlation between estradiol (E2) and GH secretory pulse amplitude, frequency, and mean 24-h serum GH concentration in the PO cycle phase, indicating E2 to be a major statistical determinant of GH secretion. Serum GH increased significantly after arginine infusion in both phases (P < 0.001), whereas there was no difference between the two cycle phases (P = 0.20). Serum IGF-I levels were increased during the PO phase (253 +/- 20 mg/L) compared to those during the EF phase (210 +/- 16 mg/L; P = 0.03), whereas serum IGF-binding protein-3, IGF-II, and GH-binding protein were similar during the two phases. This study unequivocally documents elevated GH levels during the PO phase of the menstrual cycle, mediated by increased GH production rate and burst frequency. The concomitant increase in serum IGF-I suggests a central stimulation of the GH-IGF-I axis, which may be mediated by endogenous E2 levels.

[Polycystic ovary syndrome I. Clinical presentation and treatment]. / Polycystisk ovarie-syndrome I. Klinisk billede og behandling.

Polycystic ovary syndrome (PCOS) is probably the most prevalent endocrinopathy in women and the most common cause of menstrual disturbances during the reproductive age. It is characterised by the presence of polycystic ovaries on ultrasound examination together with clinical and biochemical signs of hyperandrogenaemia. The majority of patients will seek medical advice because of menstrual disturbances, infertility or signs of hyperandrogeneamia (hirsutism, acne, alopecia). In obese patients the therapeutic mainstay is weight reduction. Anovulatory infertility is treated by stimulation of ovulation, laparoscopic electrocautery or IVF, while patients with menstrual disturbances without a wish to conceive should be treated with cyclic gestagen therapy or oral contraceptives in order to reduce the increased life-long risk of endometrial cancer. Additionally, hirsutism may be treated by epilation or antiandrogen therapy. PCOS is a common disease with an increased risk of NIDDM, hypertension, cardiovascular disease and endometrial cancer. Polycystic ovary syndrome is thus a disease which needs attention from the health system.

[Polycystic ovary syndrome II. Endocrinology and metabolism]. / Polycystisk ovarie-syndrome II. Endokrinologi og metabolisme.

The polycystic ovary syndrome (PCOS) is diagnosed by the simultaneous presence of polycystic ovaries by ultrasound together with clinical and biochemical signs of hyperandrogenaemia. Recently, it has been shown that a majority of PCO patients exhibit metabolic abnormalities, i.e. android obesity, insulin resistance and dyslipidaemia, all of which dispose to "civilized" life-style diseases such as cardiovascular disease and non-insulin dependent diabetes. PCOS is therefore not merely a gynaecological curiosity, but an endocrinopathy with multisystem sequelae. The endocrinological and metabolic aspects of the disease are discussed.

[Growth hormone treatment of men with reduced sperm quality]. / Vaeksthormonbehandling af maend med nedsat saedkvalitet.

We have treated two groups of infertile men with growth hormone (GH), namely nine oligozoospermic (< 5 x 10(6) sperm/mL) males and nine asthenozoospermic (percentage mobile sperm < 30 and > 15 x 10(6) sperm/mL) males. The patient groups had a significantly lower GH response to an arginine GH stimulation test as compared to a control group. Each patient was treated with GH for 12 weeks and followed for a total of 36 weeks with sampling of blood and semen. Sperm motility increased significantly during GH treatment in both patient groups. There was no difference in sperm count during the treatment. There were three pregnancies in the nine couples from the asthenozoospermic group and no pregnancies in the oligozoospermic group. Furthermore, we found that seminal plasma IGF-I increased simultaneously with the increase in sperm motility. These data suggest that GH stimulates IGF-I production from Sertoli and/or Leydig cells, which in a paracrine/autocrine manner stimulates maturation of spermatozoa with subsequent increased sperm motility.

Growth hormone treatment of subfertile males.

OBJECTIVE: To study spermatogenesis and sperm motility during GH therapy in infertile men. DESIGN: Prospective open study. Each patient was treated with GH for 12 weeks and followed for a total of 36 weeks with sampling of blood and semen. SETTING: Outpatients studied at a clinical research unit of a university hospital. PATIENTS: Nine oligozoospermic (<5 x 10(6) sperm/mL) males and nine asthenozoospermic (percentage motile sperm <30 and >15 x 10(6) sperm/mL) males. The patient groups had a significantly lower GH response to an arginine GH stimulation test as compared with a control group. RESULTS: Serum insulin-like growth factor I (IGF-I) and serum IGF-binding protein 3 (IGFBP-3) levels increased significantly during GH treatment, as did seminal IGF-I. Serum E2, T, PRL, FSH, LH, and GH-binding protein were unchanged during the study. Sperm motility was increased significantly during GH treatment in both patient groups. There was no difference in sperm count during the treatment. There were three pregnancies in the nine couples from the asthenozoospermic group and no pregnancies in the oligozoospermic group. CONCLUSION: The biologic and clinical results in this study encourage the initiation of double-blind, placebo-controlled trials.

Impaired growth hormone secretion and increased growth hormone-binding protein levels in subfertile males.

OBJECTIVE: To evaluate GH secretion in subfertile males. DESIGN: Comparing GH secretion to a GH stimulation test in two different patient groups and in a control group. PATIENTS: Nine oligozoospermic patients, nine asthenozoospermic patients, and nine age- and body mass index-matched fertile males with normal spermograms. INTERVENTION: All subjects underwent an IV arginine GH stimulation test. MAIN OUTCOME MEASURES: Serum levels of FSH, LH, PRL, E2, T, insulin-like growth factor I (IGF-I), and GH-binding protein were measured. RESULTS: Basal levels of GH were similar in all three groups and serum GH increased in all groups after arginine. However, there was a significant difference between the two patient groups and the control group characterized by an impaired GH response in the subfertile patients. Serum FSH and serum GH-binding protein were significantly higher in the patient groups compared with the controls. Serum LH, PRL, T, E2, and IGF-I were similar in all three groups. CONCLUSIONS: This study demonstrates that subfertile men may suffer from relative GH insufficiency, which could have therapeutical implications.

Metabolic effects of growth hormone in humans.

Growth hormone (GH) has acute actions to stimulate lipolysis and ketogenesis after 2 to 3 hours, effects that may be important in the adaptation to stress and fasting. This is accompanied by a decrease in insulin sensitivity in both liver and muscle. These combined effects may be very deleterious to insulin-dependent diabetic patients, in whom increased GH secretion may precipitate and maintain acute metabolic derangement (ketoacidosis) and be a major initiator of the dawn phenomenon. On the other hand, augmented GH secretion plays a beneficial role in the defense against hypoglycemia, in particular during prolonged hypoglycemia and in patients with impaired ability to secrete other counterregulatory hormones appropriately. It is also certain that GH is a potent anabolic hormone in terms of promoted nitrogen retention, but the extent to which these well-known actions are direct or secondary to hyperinsulinemia, increased activity of insulin-like growth factors (IGFs), or release of protein-conserving lipid intermediates has eluded precise characterization.

Somatostatin enhances insulin-stimulated glucose uptake in the perfused human forearm.

Somatostatin is widely used in experimental metabolic studies to control hormone actions. It has also been suggested that, in addition to its well known suppressive effects, somatostatin per se may increase insulin sensitivity. In order to examine this suggestion, we gave six healthy male volunteers (age 33 +/- 1 yr, mean +/- SEM; body mass index, 24.1 +/- 0.6 kg/m2) either a local intraarterial (brachial artery) or a systemic venous infusion of 25 micrograms/h somatostatin twice. The study consisted of a 1-h basal period and a 2-h systemic hyperinsulinemic (0.4 mU/kg.min) euglycemic clamp. Compared with the systemic control infusion, local forearm perfusion with somatostatin caused a 55% increase in insulin-stimulated forearm glucose uptake (0.74 +/- 0.18 vs. 0.47 +/- 0.19 mmol/L, P < 0.05). Intraarterial somatostatin perfusion did not alter basal forearm glucose uptake (0.14 +/- 0.07 vs. 0.17 +/- 0.12 mmol/L), the amount of glucose administered during the clamp (M-value, 3.2 +/- 0.5 vs. 3.0 +/- 0.6 mg/kg.min), or the levels of insulin, C-peptide, glucagon, or GH. Intermediary metabolite exchange across the forearm, total forearm blood flow, and oxygen saturations also remained stable. Glucose concentrations were slightly higher (0.06 +/- 0.01 mmol/L) in arterial than in arterialized blood, whereas lactate concentrations were comparatively decreased (108 +/- 51 mumol/L) in arterial blood. Our data suggest that somatostatin increases insulin-stimulated muscle utilization of glucose through local mechanisms. Although the nature of this increase remains to be established, it should be taken into consideration in metabolic studies using somatostatin.