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We show that jet emission from a Bose condensate with periodically driven interactions, also known as "Bose fireworks", contains essential information on the condensate wave function, which is difficult to obtain using standard detection methods. We illustrate the underlying physics with two examples. When condensates acquire phase patterns from external potentials or from vortices, the jets display novel substructure, such as oscillations or spirals, in their correlations. Through a comparison of theory, numerical simulations, and experiments, we show how one can quantitatively extract the phase and the helicity of a condensate from the emission pattern. Our work, demonstrating the strong link between jet emission and the underlying quantum system, bears on the recent emphasis on jet substructure in particle physics.
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PURPOSE: Central cancer registries collect data and provide population-level statistics that can be tracked over time; yet registries may not capture the full range of clinically relevant outcomes. Patient-generated health data (PGHD) include health/treatment history, biometrics, and patient-reported outcomes (PROs). Collection of PGHD would broaden registry outcomes to better inform research, policy, and care. However, this is dependent on the willingness of patients to share such data. This study examines cancer survivors' perspectives about sharing PGHD with central cancer registries. METHODS: Three U.S. central registries sampled colorectal, non-Hodgkin lymphoma, and metastatic breast cancer survivors 1-4 years after diagnosis, recruiting them via mail to participate in one of seven focus groups (n = 52). Group discussions were recorded, transcribed, and thematically analyzed. RESULTS: Most survivor-participants were unaware of the existence of registries. After having registries explained, all participants expressed their willingness to share PGHD with them if treated confidentially. Participants were willing to provide information on a variety of topics (e.g., medical history, medications, symptoms, financial difficulties, quality of life, biometrics, nutrition, exercise, and mental health), with a focus on long-term effects of cancer and its treatment. Participants' preferred mode for providing data varied. Participants were also interested in receiving information from registries. CONCLUSIONS: Our results suggest that registry-based collection of PGHD is acceptable to most cancer survivors and could facilitate registry-based efforts to collect PGHD/PROs. Central cancer registry-based collection of PGHD/PROs, especially on long-term effects, could enhance registry support of cancer control efforts including research and population health management.
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Supervivientes de Cáncer/psicología , Recolección de Datos/métodos , Manejo de Datos/métodos , Atención a la Salud/métodos , Medición de Resultados Informados por el Paciente , Calidad de Vida/psicología , Sistema de Registros/normas , Femenino , Grupos Focales , Humanos , Masculino , Persona de Mediana EdadRESUMEN
We demonstrate a density-dependent gauge field, induced by atomic interactions, for quantum gases. The gauge field results from the synchronous coupling between the interactions and micromotion of the atoms in a modulated two-dimensional optical lattice. As a first step, we show that a coherent shaking of the lattice in two directions can couple the momentum and interactions of atoms and break the fourfold symmetry of the lattice. We then create a full interaction-induced gauge field by modulating the interaction strength in synchrony with the lattice shaking. When a condensate is loaded into this shaken lattice, the gauge field acts to preferentially prepare the system in different quasimomentum ground states depending on the modulation phase. We envision that these interaction-induced fields, created by fine control of micromotion, will provide a stepping stone to model new quantum phenomena within and beyond condensed matter physics.
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A Bose condensate, subject to periodic modulation of the two-body interactions, was recently observed to emit matter-wave jets resembling fireworks [Nature (London) 551, 356 (2017)NATUAS0028-083610.1038/nature24272]. In this Letter, combining experiment with numerical simulation, we demonstrate that these "Bose fireworks" represent a late stage in a complex time evolution of the driven condensate. We identify a "density wave" stage which precedes jet emission and results from the interference of matter waves. The density waves self-organize and self-amplify without breaking long range translational symmetry. This density wave structure deterministically establishes the template for the subsequent patterns of the emitted jets. Moreover, our simulations, in good agreement with experiment, address an apparent asymmetry in the jet pattern, and show that it is fully consistent with momentum conservation.
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We address band engineering in the presence of periodic driving by numerically shaking a lattice containing a bosonic condensate. By not restricting to simplified band structure models we are able to address arbitrary values of the shaking frequency, amplitude, and interaction strengths g. For "near-resonant" shaking frequencies with moderate g, a quantum phase transition to a finite momentum superfluid is obtained with Kibble-Zurek scaling and quantitative agreement with experiment. We use this successful calibration as a platform to support a more general investigation of the interplay between (one particle) Floquet theory and the effects associated with arbitrary g. Band crossings lead to superfluid destabilization, but where this occurs depends on g in a complicated fashion.
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In this paper we follow the analysis and protocols of recent experiments, combined with simple theory, to arrive at a physical understanding of quasi-condensation in two dimensional Fermi gases. A key signature of quasi-condensation, which contains aspects of Berezinskii-Kosterlitz-Thouless behavior, is a strong zero momentum peak in the pair momentum distribution. Importantly, this peak emerges at a reasonably well defined onset temperature. The resulting phase diagram, pair momentum distribution, and algebraic power law decay are compatible with recent experiments throughout the continuum from BEC to BCS.
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BACKGROUND: This study examined urban-rural and socioeconomic differences in adolescent toothbrushing. METHODS: The data were modelled using logistic multilevel modelling and the Markov Chain Monte Carlo method of estimation. Twice-a-day toothbrushing was regressed upon age, family affluence, family structure, school type, area-level deprivation and rurality, for boys and girls separately. RESULTS: Boys' toothbrushing was associated with area-level deprivation but not rurality. Variance at the school level remained significant in the final model for boys' toothbrushing. The association between toothbrushing and area-level deprivation was particularly strong for girls, after adjustment for individuals' family affluence and type of school attended. Rurality too was independently significant with lower odds of brushing teeth in accessible rural areas. CONCLUSION: The findings are at odds with the results of a previous study which showed lower caries prevalence among children living in rural Scotland. A further study concluded that adolescents have a better diet in rural Scotland. In total, these studies highlight the need for an examination into the relative importance of diet and oral health on caries, as increases are observed in population obesity and consumption of sugars.
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Conducta del Adolescente/psicología , Conductas Relacionadas con la Salud , Población Rural/estadística & datos numéricos , Cepillado Dental/estadística & datos numéricos , Población Urbana/estadística & datos numéricos , Adolescente , Factores de Edad , Estudios Transversales , Femenino , Humanos , Masculino , Escocia , Factores Sexuales , Factores SocioeconómicosRESUMEN
The adolescent population of Glasgow, the city with the highest mortality in the UK, has a higher prevalence of risk behaviours than elsewhere in Scotland. Previous research has highlighted the importance of social context in interpreting such differences. Contextual variables from the 2010 Health Behaviour in School-aged Children Scotland survey were analysed. Glaswegian adolescents were more likely to live in low socioeconomic status, single-parent or step-families, or with neither parent in employment, less likely to share family meals, more likely to buy lunch outside school, and spend time with friends after school and in the evenings. They also had a poorer perception of their local neighbourhood. Family affluence only partially explained these differences.
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Conducta del Adolescente , Características de la Residencia/estadística & datos numéricos , Asunción de Riesgos , Clase Social , Medio Social , Adolescente , Familia , Femenino , Humanos , Masculino , Padres , Factores de Riesgo , Escocia , Factores SocioeconómicosRESUMEN
We present numerical simulations of phase imprinting experiments in ultracold trapped Fermi gases, which were obtained independently and are in good agreement with recent experimental results. Our focus is on the sequence and evolution of defects using the fermionic time-dependent Ginzburg-Landau equation, which contains dissipation necessary for equilibration. In contrast to other simulations, we introduce small, experimentally unavoidable symmetry breaking, particularly that associated with thermal fluctuations and with the phase-imprinting tilt angle, and we illustrate their dramatic effects. As appears consistent with experiment, the former causes vortex rings in confined geometries to move to the trap surface and rapidly decay into more stable vortex lines. The latter aligns the precessing and relatively long-lived vortex filaments, rendering them difficult to distinguish from solitons.
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AIMS/HYPOTHESIS: The molecular mechanisms underlying insulin resistance in skeletal muscle are incompletely understood. Here, we aimed to obtain a global picture of changes in protein abundance in skeletal muscle in obesity and type 2 diabetes, and those associated with whole-body measures of insulin action. METHODS: Skeletal muscle biopsies were obtained from ten healthy lean (LE), 11 obese non-diabetic (OB), and ten obese type 2 diabetic participants before and after hyperinsulinaemic-euglycaemic clamps. Quantitative proteome analysis was performed by two-dimensional differential-gel electrophoresis and tandem-mass-spectrometry-based protein identification. RESULTS: Forty-four protein spots displayed significant (p < 0.05) changes in abundance by at least a factor of 1.5 between groups. Several proteins were identified in multiple spots, suggesting post-translational modifications. Multiple spots containing glycolytic and fast-muscle proteins showed increased abundance, whereas spots with mitochondrial and slow-muscle proteins were downregulated in the OB and obese type 2 diabetic groups compared with the LE group. No differences in basal levels of myosin heavy chains were observed. The abundance of multiple spots representing glycolytic and fast-muscle proteins correlated negatively with insulin action on glucose disposal, glucose oxidation and lipid oxidation, while several spots with proteins involved in oxidative metabolism and mitochondrial function correlated positively with these whole-body measures of insulin action. CONCLUSIONS/INTERPRETATION: Our data suggest that increased glycolytic and decreased mitochondrial protein abundance together with a shift in muscle properties towards a fast-twitch pattern in the absence of marked changes in fibre-type distribution contribute to insulin resistance in obesity with and without type 2 diabetes. The roles of several differentially expressed or post-translationally modified proteins remain to be elucidated.
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Diabetes Mellitus Tipo 2/metabolismo , Resistencia a la Insulina/fisiología , Mitocondrias/metabolismo , Músculo Esquelético/metabolismo , Obesidad/metabolismo , Femenino , Técnica de Clampeo de la Glucosa , Glucólisis , Humanos , Insulina/metabolismo , Masculino , Persona de Mediana Edad , Proteómica , Espectrometría de Masas en TándemRESUMEN
BACKGROUND: Improving the diet of the Scottish population has been a government focus in recent years. Health promotion is known to be more effective in affluent groups. Alongside trends in eating behaviour, changes in socioeconomic inequalities must be monitored. METHODS: Eating behaviour data from the 2002, 2006 and 2010 Scotland Health Behaviour in School-Aged Children survey were modelled using multilevel linear modelling. RESULTS: Fruit and vegetable consumption increased between 2002 and 2010 by 0.26 and 0.27 days per week, respectively, while consumption of sweets, chips and crisps fell by 0.73, 1.25 and 0.99 days per week, respectively. An overall healthy eating score, calculated by summing food item weekly consumption, increased significantly (at 95% level of significance) over this period. Fruit and vegetable consumption was more frequent among children with high family affluence (individual measure of socioeconomic status), while consumption of crisps and chips was less frequent. When an interaction term was added between year and family affluence, this was not significant for any outcome. Variance at the education authority and school levels remained significant for all outcomes. CONCLUSIONS: Adolescent eating behaviours in Scotland have improved over time across the family affluence scale gradient as a whole, with persistent inequalities. Alongside population programmes, initiatives directed at more deprived groups are required.
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Conducta del Adolescente , Dieta/tendencias , Conducta Alimentaria , Conductas Relacionadas con la Salud , Adolescente , Niño , Estudios Transversales , Dieta/estadística & datos numéricos , Encuestas sobre Dietas , Grasas de la Dieta , Sacarosa en la Dieta , Composición Familiar , Femenino , Frutas , Humanos , Modelos Lineales , Masculino , Escocia , Factores Socioeconómicos , VerdurasRESUMEN
BACKGROUND: The existence of a negative 'Glasgow effect' on health has been much disputed. Previously, Glasgow's poor health was believed to be due to high levels of poverty. However, more recent studies investigating adult health outcomes have shown an effect over and above that of deprivation. OBJECTIVES: To examine the existence of a 'Glasgow effect' on mental well-being and subjective health of an adolescent sample. STUDY DESIGN: Data from the 2006 Health Behaviour in School-Aged Children cross-sectional survey were analyzed. METHODS: Data were modelled using multilevel logistic and linear modelling for the following outcomes: happiness, confidence, feeling left out, self-rated health, multiple health complaints (MHC), life satisfaction and health-related quality of life (KIDSCREEN-10). The models were further adjusted for family affluence and family status, as proxy measures of socio-economic status. RESULTS: The proportions of pupils that reported being very happy, always confident and never left out were greater among pupils in Glasgow compared with pupils in the rest of Scotland, as were mean life satisfaction and KIDSCREEN scores. Frequencies of MHC and subjective health were not significantly different in Glasgow compared with the rest of Scotland. Similar results were observed following the modelling procedures, adjusting for age, sex, grade and school type (state or independent), for all outcomes other than life satisfaction, and effect sizes increased further after adjustment for family affluence and family status. The odds of a pupil in Glasgow being very happy, for example, were 1.48 [credible interval (CI) 1.19-1.83] those of a pupil outside Glasgow. After adjustment for family affluence and family status, the odds were 1.59 (CI 1.28-1.98). An interaction term between Glasgow and grade was not significant for all mental well-being outcomes, although there was some suggestion that a negative Glasgow effect on self-rated health is emerging by Secondary 4. CONCLUSIONS: The Glasgow effect may not be all bad. The findings suggest that mental well-being is more prevalent in Glasgow compared with the rest of Scotland during adolescence. Further research is recommended to investigate the Glasgow effect during this life stage.
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Salud Mental , Psicología del Adolescente , Calidad de Vida , Adolescente , Estudios Transversales , Recolección de Datos , Femenino , Felicidad , Estado de Salud , Humanos , Masculino , Escocia , Clase SocialRESUMEN
Recent experiments on the shear viscosity η in a unitary Fermi gas fail to see the theoretically predicted upturn in η at the lower T. In this Letter, we compute η in a fashion which is demonstrably consistent with conservation laws and, in the process, provide an understanding of recent experiments. We show that this disagreement with prior theories cannot be readily attributed to the trap, since (via edge effects) trap-averaged viscosities will be larger than their homogeneous counterparts. The small values of η we find can be simply understood; they reflect the fact that the Goldstone bosons (phonons) do not couple to transverse probes such as η, and fermionic excitations, which determine the viscosity, are necessarily absent in the ground state.
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AIMS/HYPOTHESIS: Insulin resistance in skeletal muscle is linked to mitochondrial dysfunction in obesity and type 2 diabetes. Emerging evidence indicates that reversible phosphorylation regulates oxidative phosphorylation (OxPhos) proteins. The aim of this study was to identify and quantify site-specific phosphorylation of the catalytic beta subunit of ATP synthase (ATPsyn-beta) and determine protein abundance of ATPsyn-beta and other OxPhos components in skeletal muscle from healthy and insulin-resistant individuals. METHODS: Skeletal muscle biopsies were obtained from lean, healthy, obese, non-diabetic and type 2 diabetic volunteers (each group n = 10) for immunoblotting of proteins, and hypothesis-driven identification and quantification of phosphorylation sites on ATPsyn-beta using targeted nanospray tandem mass spectrometry. Volunteers were metabolically characterised by euglycaemic-hyperinsulinaemic clamps. RESULTS: Seven phosphorylation sites were identified on ATPsyn-beta purified from human skeletal muscle. Obese individuals with and without type 2 diabetes were characterised by impaired insulin-stimulated glucose disposal rates, and showed a approximately 30% higher phosphorylation of ATPsyn-beta at Tyr361 and Thr213 (within the nucleotide-binding region of ATP synthase) as well as a coordinated downregulation of ATPsyn-beta protein and other OxPhos components. Insulin increased Tyr361 phosphorylation of ATPsyn-beta by approximately 50% in lean and healthy, but not insulin-resistant, individuals. CONCLUSIONS/INTERPRETATION: These data demonstrate that ATPsyn-beta is phosphorylated at multiple sites in human skeletal muscle, and suggest that abnormal site-specific phosphorylation of ATPsyn-beta together with reduced content of OxPhos proteins contributes to mitochondrial dysfunction in insulin resistance. Further characterisation of phosphorylation of ATPsyn-beta may offer novel targets of treatment in human diseases with mitochondrial dysfunction, such as diabetes.
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Resistencia a la Insulina , ATPasas de Translocación de Protón Mitocondriales/química , Músculos/metabolismo , Adulto , Sitios de Unión , Catálisis , Estudios de Cohortes , Femenino , Humanos , Insulina/metabolismo , Masculino , Persona de Mediana Edad , ATPasas de Translocación de Protón Mitocondriales/metabolismo , Músculo Esquelético/metabolismo , Músculo Esquelético/patología , Fosforilación , Tirosina/químicaRESUMEN
We show how in ultracold Fermi gases the difference between the finite temperature T structure factors, called S_(ω,q), associated with spin and density, reflects coherent order at all ω, q, k(F)a, and T. This observation can be exploited in two photon Bragg scattering experiments on gases which are subject to variable attractive interactions. Our calculations incorporate spin and particle number conservation laws which lead to compatibility at general T with two f-sum rules. Because of its generality a measurement of S_(ω,q) can be a qualitative, direct, in situ approach for establishing superfluid order.
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AIMS: To assess the effect of liraglutide, a once-daily human glucagon-like peptide-1 analogue on pancreatic B-cell function. methods: Patients with Type 2 diabetes (n = 39) were randomized to treatment with 0.65, 1.25 or 1.9 mg/day liraglutide or placebo for 14 weeks. First- and second-phase insulin release were measured by means of the insulin-modified frequently sampled intravenous glucose tolerance test. Arginine-stimulated insulin secretion was measured during a hyperglycaemic clamp (20 mmol/l). Glucose effectiveness and insulin sensitivity were estimated by means of the insulin-modified frequently sampled intravenous glucose tolerance test. RESULTS: The two highest doses of liraglutide (1.25 and 1.9 mg/day) significantly increased first-phase insulin secretion by 118 and 103%, respectively (P < 0.05). Second-phase insulin secretion was significantly increased only in the 1.25 mg/day group vs. placebo. Arginine-stimulated insulin secretion increased significantly at the two highest dose levels vs. placebo by 114 and 94%, respectively (P < 0.05). There was no significant treatment effect on glucose effectiveness or insulin sensitivity. CONCLUSIONS: Fourteen weeks of treatment with liraglutide showed improvements in first- and second-phase insulin secretion, together with improvements in arginine-stimulated insulin secretion during hyperglycaemia.
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Diabetes Mellitus Tipo 2/tratamiento farmacológico , Péptido 1 Similar al Glucagón/análogos & derivados , Hipoglucemiantes/uso terapéutico , Islotes Pancreáticos/metabolismo , Receptores de Glucagón/metabolismo , Péptido C/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Esquema de Medicación , Femenino , Péptido 1 Similar al Glucagón/uso terapéutico , Humanos , Incretinas/metabolismo , Resistencia a la Insulina , Liraglutida , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
Patients with type 2 diabetes (T2D) and their first-degree relatives (FDRs) are characterized by hypoadiponectinaema and insulin resistance. In T2D patients, plasma adiponectin and insulin sensitivity (SI) increase in response to thiazolidinediones (TZDs). These findings suggest a role for adiponectin in the regulation of SI. We studied the relationship between plasma adiponectin and glucose and lipid metabolism and the effect of troglitazone (200 mg/day) for 12 weeks in 19 normoglycaemic, obese FDR and 20 obese T2D patients, using euglycaemic-hyperinsulinaemic clamps, glycolytic flux calculations and indirect calorimetry. Plasma adiponectin was similar in both groups, despite higher glucose disposal (Rd), glucose oxidation and glycolytic flux and lower lipid oxidation during insulin stimulation in FDR compared with T2D patients. Plasma adiponectin correlated with insulin-stimulated Rd, non-oxidative glucose disposal (NOGD), glucose storage and SI in both groups after adjustment for sex and body fat. The troglitazone-mediated upregulation of plasma adiponectin was associated with increased insulin-stimulated Rd, NOGD and glucose storage in both groups. No effect on endogenous glucose production was observed. In FDR, plasma adiponectin correlated with insulin-stimulated glycogen synthase activity and the troglitazone-induced increase in plasma adiponectin correlated with the improvement in insulin-stimulated Rd and SI after adjustment for sex and body fat. In conclusion, plasma adiponectin in weight-matched FDR and T2D patients is comparably low and correlates with insulin-mediated glucose uptake and storage. Moreover, these data provide evidence for an adiponectin-dependent insulin-sensitizing effect of TZDs at an early stage before development of T2D and that this effect is exerted mainly on insulin-mediated glucose metabolism.
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Adiponectina/sangre , Hijos Adultos , Cromanos/uso terapéutico , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Tiazolidinedionas/uso terapéutico , Adulto , Análisis de Varianza , Glucemia/análisis , Diabetes Mellitus Tipo 2/enzimología , Femenino , Técnica de Clampeo de la Glucosa , Glucógeno Sintasa/análisis , Humanos , Insulina/sangre , Insulina/uso terapéutico , Masculino , Persona de Mediana Edad , Músculos/química , Triglicéridos/sangre , TroglitazonaRESUMEN
OBJECTIVE: This study examines mean length of stay (LOS) and rates of emergency bed days during the course of the Reshaping Care for Older People (RCOP) programme in Glasgow City. METHODS: An ecological small-area study design was used. Standardised monthly rates of bed days and LOS were calculated, between April 2011 and March 2015, for residents of Glasgow City aged 65 years and over. Multilevel negative binomial models for the square root of each outcome nested by datazone were created, adjusting for sex, 5-year age group, area-level deprivation, season, month and month squared. Relative index of inequality (RII) and slope index of inequality (SII) were calculated for each year and the trend was examined. RESULTS: The rate of bed days first rose then fell during the study period, while LOS first fell then rose. Relative risk (RR) of an additional bed day was greater for males (RR=1.14 (1.12, 1.16)) and increased with increasing age group. There was no gender difference in LOS. Bed days per head of population first increased then fell; for 12-month period RR=1.01 (0.98, 1.05) and for 12-month period squared, RR=0.999 (0.999, 0.999). RII and SII for rate of bed days per head of population were significant, though not for LOS. SII for bed days per head of population did not change significantly over time, while RII reduced at the 87% level of confidence. CONCLUSIONS: The results suggest a reduction in secondary care use by older people during the RCOP programme, and a possible reduction in socioeconomic inequalities in bed days in the longer term.
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Hospitalización/tendencias , Adolescente , Adulto , Anciano , Niño , Preescolar , Recolección de Datos , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Riesgo , Escocia , Factores Socioeconómicos , Adulto JovenRESUMEN
Defects in hepatic insulin action in type 2 diabetes and its possible underlying mechanisms were assessed in euglycemic-hyperinsulinemic clamp studies, using improved tracer methods (constant specific activity technique). Ten obese diabetic patients (age 54 years, BMI 29 +/- 0.5 kg/m(2)) and ten matched control subjects were studied at baseline (after an overnight fast) and during insulin infusions of 20- and 40-mU. m(-2). min(-1). In the diabetic patients, plasma glucose levels were normalized overnight before the studies by low-dose insulin infusion. Hepatic sinusoidal insulin levels were estimated, and plasma levels of free fatty acids (FFAs) and glucagon were determined to assess the direct and indirect effects of insulin on hepatic glucose production (HGP) in type 2 diabetes. Baseline rates of HGP (86 +/- 3 vs. 76 +/- 3 mg. m(-2). min(-1), P < 0.05) were slightly elevated in the diabetic patients compared with control subjects, despite much higher hepatic sinusoidal insulin levels (26 +/- 3 vs. 12 +/- 2 mU/l, P < 0.001). Consequently, a marked defect in the direct (hepatic) effect of insulin on HGP appeared to be present at low insulin levels. However, in response to a small increase in baseline hepatic sinusoidal insulin levels of 11 mU/l (26 +/- 3 to 37 +/- 3 mU/l, P < 0.05) in the 20-mU clamp, a marked suppression of HGP was observed in the diabetic patients (86 +/- 3 to 32 +/- 5 mg. m(-2). min(-1), P < 0.001), despite only minimal changes in FFAs (0.33 +/- 0.05 to 0.25 +/- 0.05 mmol/l, NS) and glucagon (14 +/- 1 to 11 +/- 2 pmol/l, P < 0.05) levels, suggesting that the impairment in the direct effect of insulin can be overcome by a small increase in insulin levels. Compared with control subjects, suppression of HGP in the diabetic patients was slightly impaired in the 20-mU clamp (32 +/- 5 vs. 22 +/- 4 mg. m(-2). min(-1), P < 0.05) but not in the 40-mU clamp (25 +/- 2 vs. 21 +/- 3 mg. m(-2). min(-1), NS). In the 20-mU clamp, hepatic sinusoidal insulin levels in the diabetic patients were comparable with control subjects (37 +/- 3 vs. 36 +/- 3 mU/l, NS), whereas both FFA and glucagon levels were higher (i.e., less suppressed) and correlated with the rates of HGP (R = 0.71, P < 0.02; and R = 0.69, P < 0.05, respectively). Thus, at this insulin level impaired indirect (extrahepatic) effects of insulin seemed to prevail. In conclusion, hepatic insulin resistance is present in obese type 2 diabetic patients but is of quantitative significance only at low physiological insulin levels. Defects in both the direct and the indirect effects of insulin on HGP appear to contribute to this resistance.