Experimental generation of a flat-top beam profile in a stable ring cavity.

In this Letter, we present a spatially homogeneous field inside of a ring cavity that was created by combining two transverse modes generated by a single laser through modulation. The interference term between the two modes averages out because of the frequency difference that exists between them, eliminating the need for interferometric control of their relative phase. The use of a ring cavity allows for a large waist for the flat-top profile, big enough to cover the atoms in an atomic trap. The cavity is mechanically and thermally isolated, and the laser light is locked to the cavity using the Pound-Drever-Hall technique. The flat-top profile technique reported here fulfills the vanishing curvature criterion at the center of the profile.

Experimental characterization of two spatial qutrits using entanglement witnesses.

We present an experimental technique for a complete characterization of entanglement in a two-qutrit state generated using transverse spatial correlations of two parametric down-converted photons. We verify entanglement for a particular case via entanglement witness operators which are decomposed into a sum of local observables of single path and superposition projection operators. Experimentally, these operators are accomplished by using a spatial light modulator and a polarizing beam splitter which allow to modulate the amplitude of individually chosen path states. The quantification of entanglement is computed by the negativity obtained from the expectation values of the entanglement witnesses implemented.

Minimal state tomography of spatial qubits using a spatial light modulator.

We report minimal quantum state tomography with spatial qubits created by a pair of parametric down converted twin-photons passing through a double-slit. A novel experimental setup is used, which includes a Spatial Light Modulator, as a fundamental tool, to reconstruct the state density matrix. The theory needed to perform a minimal quantum tomography is described. The density matrix is experimentally obtained for the two-qubit photonic states in spatial variables.

Use of the oral glucose tolerance test to assess insulin release and insulin sensitivity.

OBJECTIVE: The oral glucose tolerance test (OGTT) has often been used to evaluate apparent insulin release and insulin resistance in various clinical settings. However, because insulin sensitivity and insulin release are interdependent, to what extent they can be predicted from an OGTT is unclear. RESEARCH DESIGN AND METHODS: We studied insulin sensitivity using the euglycemic-hyperinsulinemic clamp and insulin release using the hyperglycemic clamp in 104 nondiabetic volunteers who had also undergone an OGTT. Demographic parameters (BMI, waist-to-hip ratio, age) and plasma glucose and insulin values from the OGTT were subjected to multiple linear regression to predict the metabolic clearance rate (MCR) of glucose, the insulin sensitivity index (ISI), and first-phase (1st PH) and second-phase (2nd PH) insulin release as measured with the respective clamps. RESULTS: The equations predicting MCR and ISI contained BMI, insulin (120 min), and glucose (90 min) and were highly correlated with the measured MCR (r = 0.80, P < 0.00005) and ISI (r = 0.79, P < 0.00005). The equations predicting 1st PH and 2nd PH contained insulin (0 and 30 min) and glucose (30 min) and were also highly correlated with the measured 1st PH (r = 0.78, P < 0.00005) and 2nd PH (r = 0.79, P < 0.00005). The parameters predicted by our equations correlated better with the measured parameters than homeostasis model assessment for secretion and resistance, the delta30-min insulin/delta30-min glucose ratio for secretion and insulin (120 min) for insulin resistance taken from the OGTT. CONCLUSIONS: We thus conclude that predicting insulin sensitivity and insulin release with reasonable accuracy from simple demographic parameters and values obtained during an OGTT is possible. The derived equations should be used in various clinical settings in which the use of clamps or the minimal model would be impractical.

Experimental simulation of decoherence in photonics qudits.

We experimentally perform the simulation of open quantum dynamics in single-qudit systems. Using a spatial light modulator as a dissipative optical device, we implement dissipative-dynamical maps onto qudits encoded in the transverse momentum of spontaneous parametric down-converted photon pairs. We show a well-controlled technique to prepare entangled qudits states as well as to implement dissipative local measurements; the latter realize two specific dynamics: dephasing and amplitude damping. Our work represents a new analogy-dynamical experiment for simulating an open quantum system.

Simultaneous assessment of insulin secretion and insulin sensitivity using a hyperglycemia clamp.

A hyperglycemic clamp is an established method to assess insulin secretion and is generally used only for this purpose. To determine whether it could also be used to assess insulin sensitivity, we compared insulin sensitivity indices (ISI) obtained during euglycemic and hyperglycemic clamp experiments in 22 nonobese volunteers (body mass index, 23.9 +/- 0.6 kg/m2) and in 20 obese individuals (body mass index, 30.8 +/- 1.3 kg/m2) matched for age and gender. The ISI values (micromoles per kg.min/pmol) of the obese group assessed during hyperglycemic (0.088 +/- 0.011) and euglycemic (0.050 +/- 0.005) clamp experiments were both significantly lower than the ISI of the nonobese group assessed in hyperglycemic and euglycemic clamp experiments (0.179 +/- 0.024 and 0.096 +/- 0.009, respectively; both P less than 0.01). Although the ISI values obtained with hyperglycemic clamps were consistently greater than those obtained with euglycemic clamp (0.137 +/- 0.016 vs. 0.075 +/- 0.007; P less than 0.001), they were highly correlated (r = 0.84; P less than 0.0001). Moreover, when these indices were converted to clearance rates, thereby correcting for the mass action effects of glucose on glucose disposal, the values obtained with the hyperglycemic clamp (0.0137 +/- 0.0016 mL/kg.min/pmol) were statistically identical to those obtained with the euglycemic clamp (0.0142 +/- 0.0013 mL/kg.min/pmol), as indicated by a regression equation having an intercept of 0 and a slope (1.03) not different from 1. We, therefore, conclude that the hyperglycemic clamp and the euglycemic clamp yield comparable estimates of insulin sensitivity and that, under appropriate conditions, the hyperglycemic clamp technique may be used to assess both insulin sensitivity and insulin secretion in the same individual in a single experiment.

Peripheral glucose metabolism in human hyperthyroidism.

The present study was designed to determine the effect of spontaneous hyperthyroidism on the forearm muscle glucose uptake and oxidation during the postabsorptive state and after an oral glucose challenge. Ten normal subjects and 11 hyperthyroid patients were studied after an overnight fast (12-14 h) and for 3 h after ingestion of 75 g glucose. Peripheral glucose metabolism was analyzed by the forearm technique to estimate muscle exchange of substrate combined with indirect calorimetry. Increased forearm glucose uptake was observed in the hyperthyroid patients compared to that in the normal subjects (1286 +/- 212 vs. 677 +/- 88 mumol/100 mL forearm.3 h) with enhanced glucose oxidation (443 +/- 40 vs. 147 +/- 29 mumol/100 mL forearm.3 h). Nonoxidative glucose metabolism was also greater in hyperthyroid patients than in normal subjects (842 +/- 234 vs. 529 +/- 90 mumol/100 mL forearm.3 h). Basal serum FFA levels were significantly higher in hyperthyroid than in normal subjects (0.252 +/- 0.025 vs. 0.182 +/- 0.022 g/L), as were the basal lipid oxidation rates in the forearm muscles of the thyrotoxic individuals (0.290 +/- 0.066 vs. 0.088 +/- 0.016 mg/100 mL forearm.min). After glucose ingestion, serum FFA levels and lipid oxidation rates declined significantly to equivalent values in both groups of subjects, and the similar basal insulin concentrations increased to significantly higher levels in the hyperthyroid patients. In conclusion, spontaneous human hyperthyroidism increases glucose uptake by the forearm muscles in the postabsorptive state and during an oral glucose challenge, with augmented fluxes of glucose through the oxidative and nonoxidative pathways.

Relative conributions of beta-cell function and tissue insulin sensitivity to fasting and postglucose-load glycemia.

We performed hyperglycemic clamps in 283 nondiabetic Caucasians and, with multiple linear regression, determined the contribution of beta-cell function and tissue insulin sensitivity to variations in glycemia and insulinemia during oral glucose tolerance tests (OGTTs). Impaired glucose tolerance (IGT) subjects had reduced insulin sensitivity (P < .02) and beta-cell function (P < .0001). Normal glucose tolerance (NGT) subjects with first-degree type 2 diabetic relatives had reduced first and second phase insulin secretion (both, P < .05), but normal insulin sensitivity (P = .37). Beta-Cell function and insulin sensitivity accounted for one fourth of the variability in glucose tolerance. Fasting plasma glucose in subjects with NGT (n = 185) was a function of both phases of insulin secretion and of insulin sensitivity (all, P < .05), whereas, in IGT subjects (n = 98), it was a function of first phase insulin secretion and insulin sensitivity (P < .01). Two-hour glycemia was a function of second phase secretion and insulin sensitivity (P < .01). Fasting and 2-hour plasma insulin levels were determined by insulin sensitivity (and glycemia) in NGT subjects (P < .001), but by second phase secretion in IGT (P < .001). We conclude that beta-cell function is reduced in subjects with IGT; glycemia and insulinemia are not regulated by the same mechanisms in IGT and NGT; insulin sensitivity does not contribute to insulinemia in IGT; family history of diabetes influences beta-cell function, but not insulin sensitivity in Caucasians.

Brazilian individuals with impaired glucose tolerance are characterized by impaired insulin secretion.

BACKGROUND: To better understand the pathogenesis of type 2 diabetes mellitus, insulin secretion and insulin sensitivity (IS) were evaluated in white Brazilians with impaired glucose tolerance (IGT), using the oral glucose tolerance test (OGTT) and the hyperglycemic clamp technique. METHODS: Twenty-five IGT subjects were individually matched with normal glucose-tolerant (NGT) subjects for demographic characteristics. At first, they were submitted to the OGTT and plasma glucose and insulin were measured. Of the 25 pairs, 20 could participate in the hyperglycemic clamp procedures, at a second visit. All participants had their plasma glucose levels equally increased to 180 mg/dl; this was maintained for three hours by variable glucose infusion. During the procedure, plasma glucose and insulin were measured at established intervals. RESULTS: In the postabsorptive state, the IGT subjects presented higher levels of plasma glucose, blood HbA1, and serum triglycerides, but similar plasma insulin levels. After the oral glucose load, early and total insulin release, in relation to glucose levels, were respectively, 43 and 67% lower in the IGT individuals. The index of whole-body IS was increased in the IGT individuals (4.36 +/- 1.71 vs 3.61 +/- 1.28 mg(-1). micro U(-1).100.ml2; p<0.05). By the hyperglycemic clamp technique first- (82 +/- 26 vs 215 +/- 88 micro U/ml; p<0.001) and second- (36 +/- 19 vs 73 +/- 44 micro U/ml; p<0.05) phases of insulin secretion was decreased in the IGT individuals, especially the first one. However, the groups did not differ in relation to the IS: IGT=13.52 +/- 7.27 and NGT=9.96 +/- 6.70 mg.ml/kg. micro U.min(-1); p > 0.05. Functional relationship of IS (y) on first-phase insulin release (x) showed a smaller (p<0.05) regression coefficient for the IGT group. CONCLUSION: Brazilians with IGT well-matched with NGT ones were characterized by impaired first- and second-phase insulin secretion (mainly the former), while defects in IS were not evident.

Pancreatic beta-cell defects in women at risk of type 2 diabetes.

We evaluated insulin release and insulin sensitivity in women with basal and/or postprandial hyperglycemia but normal oral glucose tolerance test (OGTT) in previous pregnancy (GHG). These women were individually matched with females without previous hyperglycemia (NGT). Both groups consisted of normal glucose-tolerant women at the time of this study. They underwent OGTT (75 g; n=32 pairs) and hyperglycemic clamp experiments (10 mmoll(-1); n=27 pairs) with plasma glucose, insulin, and C-peptide measurements and calculation of insulinogenic index, first- and second-phase insulin release, and insulin sensitivity index (ISI). The GHG group showed higher glycosylated hemoglobin levels (6.2+/-0.6% versus 5.8+/-0.8%; P<0.05); lower insulinogenic index at 30 min (134.03+/-62.69 pmol mmol(-1) versus 181.59+/-70.26 pmol mmoll(-1); P<0.05) and diminished C-peptide response in relation to glucose (4.05+/-0.36 nmol mmol(-1) versus 4.23+/-0.36 nmol mmol(-1); P<0.05) at OGTT. Both groups did not show difference in insulin secretion and ISI by hyperglycemic clamp technique. We concluded that in up to 12 years from index pregnancy, women with previous GHG, presenting normal glucose tolerance and well-matched with their controls, showed beta-cell dysfunction without change in ISI. As women with previous GHG are at risk of type 2 diabetes, beta-cell dysfunction may be its primary defect.

Effect of oral glucose on peripheral muscle fuel metabolism in fasted men.

1. The metabolic adaptations of peripheral muscle during a 5-day "modified" fast (daily oral intake of 200 g of glucose) were studied in 12 normal males. The volunteers were studied initially after receiving a balanced 2,400-kcal diet for at least 3 days (S1) and then after 5 days of modified fast (S2). The forearm muscle exchange of energy substrate (glucose) and the carbohydrate and lipid oxidation rates in muscle were measured during the postabsorptive state (S1) and after an oral glucose challenge (S2). 2. Glucose intolerance was not observed in either situation. Arterial glucose levels increased from a basal value of 83 mg/100 ml to 171 mg/100 ml in S1 and to 187 mg/100 ml in S2 at 30 and 60 min, respectively, and returned to basal values at 180 min in both studies. Increased forearm glucose uptake was observed in S2 compared to S1 (121.7 +/- 17.1 vs 92.6 +/- 12.0 mg 100 ml forearm-1 3 h-1), with decreased glucose oxidation (23.8 +/- 3.7 vs 30.4 +/- 4.7 mg 100 ml forearm-1 3 h-1) and increased glucose storage (98.0 +/- 16.6 vs 62.2 +/- 10.8 mg 100 ml forearm-1 3 h-1) as muscle glycogen. 3. Basal serum free fatty acid (FFA) levels were significantly more elevated in S2 than S1 (1030 +/- 95 vs 657 +/- 59 mumol/l; P less than 0.05) but were markedly reduced by glucose ingestion in both studies (352 +/- 33 (S2) vs 364 +/- 30 (S1) mumol/l at 120 min). Basal FFA oxidation was similar in both studies (0.091 +/- 0.015 (S1) vs 0.105 +/- 0.019 (S2) mg 100 ml forearm-1 min-1) and decreased significantly 3 h after glucose ingestion only in S1 (0.030 +/- 0.010 (S1) vs 0.078 +/- 0.020 (S2) mg 100 ml forearm-1 min-1; P less than 0.05). 4. The insulin response to oral glucose was similar in both studies (11,060 +/- 899 (S1) vs 11,078 +/- 918 (S2) microU ml-1 3 h-1), but the peak concentration occurred later (60 min (S2) vs 30 min (S1] and basal levels were significantly lower in S2 compared to S1 (9.2 +/- 1.7 vs 11.1 +/- 1.5 microU/ml; P less than 0.05). 5. These data show that the metabolic adaptations of normal subjects to a 5-day "modified" fast (daily oral intake of 200 g glucose) were increased muscle uptake of glucose, with reduced glucose oxidation and increased glucose storage in the form of muscle glycogen.

Insulin secretion, insulin sensitivity, and hepatic insulin extraction in first-degree relatives of type 2 diabetic patients.

To identify early metabolic abnormalities in type 2 diabetes mellitus, we measured insulin secretion, sensitivity to insulin, and hepatic insulin extraction in 48 healthy normal glucose-tolerant Brazilians, first-degree relatives of type 2 diabetic patients (FH+). Each individual was matched for sex, age, weight, and body fat distribution with a person without history of type 2 diabetes (FH-). Both groups were submitted to a hyperglycemic clamp procedure (180 mg/dl). Insulin release was evaluated in its two phases. The first was calculated as the sum of plasma insulin at 2.5, 5.0, 7.5, and 10.0 min after the beginning of glucose infusion, and the second as the mean plasma insulin level in the third hour of the clamp procedure. Insulin sensitivity index (ISI) was the mean glucose infusion rate in the third hour of the clamp experiment divided by the mean plasma insulin concentration during the same period of time. Hepatic insulin extraction was determined under fasting conditions and in the third hour of the clamp procedure as the ratio between C-peptide and plasma insulin levels. FH+ individuals did not differ from FH- individuals in terms of the following parameters [median (range)]: a) first-phase insulin secretion, 174 (116-221) vs 207 (108-277) microU/ml, b) second-phase insulin secretion, 64 (41-86) vs 53 (37-83) microU/ml, and c) ISI, 14.8 (9.0-20.8) vs 16.8 (9.0-27.0) mg kg-1 min-1/ microU ml-1. Hepatic insulin extraction in FH+ subjects was similar to that of FH- ones at basal conditions (median, 0.27 vs 0.27 ng/microU) and during glucose infusion (0.15 vs 0.15 ng/ micro U). Normal glucose-tolerant Brazilian FH+ individuals well-matched with FH- ones did not show defects of insulin secretion, insulin sensitivity, or hepatic insulin extraction as tested by hyperglycemic clamp procedures.

Hormonal and metabolic study of a case of adiposis dolorosa (Dercum's disease).

A case of a 43-year-old nonobese woman with adiposis dolorosa (Dercum's disease) is reported. Muscle glucose uptake and oxidation before and after ingestion of 75 g of glucose were similar to control group values, although a greater insulin release (16,578 vs 6,242 +/- 1,136 microU/3 h) occurred simultaneously. In vitro studies of abdominal normal and painful subcutaneous adipose tissue of the patient revealed lower responsiveness to norepinephrine and lack of response to the antilipolytic effect of insulin in the painful adipose tissue (0.98 vs 1.43 microM FFA/10(6) cells at 5.0 microM of norepinephrine). The disease was not correlated with the HLA system and there were no alterations in hormonal secretion at the pituitary, adrenal, gonadal, and thyroid levels. These findings indicate the presence of peripheral insulin resistance in this patient with adiposis dolorosa.

Zinc acutely and temporarily inhibits adrenal cortisol secretion in humans. A preliminary report.

Hypo- and hyperzincemia has been reported to cause alterations in the adrenal secretion. To determine the acute effect of zinc on cortisol levels, we studied 27 normal individuals of both sexes aged 20-27 y after a 12-h fast. The tests were initiated at 7:00 AM when an antecubital vein was punctured and a device for infusion was installed and maintained with physiological saline. Zinc was administered orally at 8:00 AM. Subjects were divided into an experimental group of 13 individuals who received doses of 25, 37.5, and 50 mg of zinc and a control group of 14 individual who received 20 mL of physiological saline. Serial blood samples were collected over a period of 240 min after basal samples (-30 and 0 min). We detected an acute inhibitory effect of zinc on cortisol secretion during 240 min of the study period in the experimental group.

[Arterial dysfunction as a possible mechanism of cardiac injury in type II diabetic patients. A Doppler-echocardiographic study]. / Disfunção arterial como possível mecanismo de agressão cardíaca em pacientes com diabetes mellitus tipo II. Estudo Doppler-ecocardiográfico.

PURPOSE: To evaluate the left ventricular structure and function and the arterial stiffness in type II diabetic patients. METHODS: Thirteen diabetic patients, men and women (age 55 +/- 8 years) were included in the study. None of the patients had any other clinical disorders. Doppler-echocardiography and non-invasive monitoring of arterial blood pressure were performed. All the results were compared to an age and sex matched control group (n = 12). RESULTS: There were no differences between the groups for diastolic blood pressure, dimensions of cardiac chambers and ventricular systolic and diastolic function indexes. Diabetic patients had increased left ventricular mass index (101 +/- 10 vs 80 +/- 14 g/m2; p < 0.001) and increased arterial stiffness (0.86 +/- 0.26 vs 0.69 +/- 0.19 mmHg/mL; p < 0.05), when compared to control group. CONCLUSION: Diabetes mellitus is associated to increased systemic arterial stiffness and this may contribute to the adverse effects of diabetes on left ventricular morphology.

Demographic and metabolic characteristics of individuals with progressive glucose tolerance.

We evaluated changes in glucose tolerance of 17 progressors and 62 non-progressors for 9 years to improve our understanding of the pathogenesis of type 2 diabetes mellitus. Changes in anthropometric measurements and responses to an oral glucose tolerance test (OGTT) were analyzed. We identified 14 pairs of individuals, one from each group, who were initially normal glucose tolerant and were matched for gender, age, weight, and girth. We compared initial plasma glucose and insulin curves (from OGTT), insulin secretion (first and second phases) and insulin sensitivity indices (from hyperglycemic clamp assay) for both groups. In the normal glucose tolerant phase, progressors presented: 1) a higher OGTT blood glucose response with hyperglycemia in the second hour and a similar insulin response vs non-progressors; 2) a reduced first-phase insulin secretion (2.0 +/- 0.3 vs 2.3 +/- 0.3 pmol/L; P < 0.02) with a similar insulin sensitivity index and a lower disposition index (3.9 +/- 0.2 vs 4.1 +/- 0.2 micromol.kg-1.min-1 ; P < 0.05) vs non-progressors. After 9 years, both groups presented similar increases in weight and fasting blood glucose levels and progressors had an increased glycemic response at 120 min (P < 0.05) and reduced early insulin response to OGTT (progressors, 1st: 2.10 +/- 0.34 vs 2nd: 1.87 +/- 0.25 pmol/mmol; non-progressors, 1st: 2.15 +/- 0.28 vs 2nd: 2.03 +/- 0.39 pmol/mmol; P < 0.05). Theses data suggest that beta-cell dysfunction might be a risk factor for type 2 diabetes mellitus.

Increased glucose synthesis in renal tubule fragments from hyperthyroid rats.

Rates of glucose synthesis from several substrates were examined in renal tubule fragments from hyperthyroid rats. A hyperthyroid state was induced by daily intraperitoneal injections of thyroxine (T4) (100 microg/100 g body weight) for 14 days. At the end of the experimental period, plasma triiodothyronine and T4 levels were six and eight times higher, respectively, than initial values. Hyperthyroid rats gained less weight and had lower blood glucose despite an increased food intake. In both control and hyperthyroid rats, rates of glucose production by renal tubule fragments were higher with glutamine and glycerol than with lactate, alanine, or glutamate. T4 treatment induced a significant increase in the de novo glucose synthesis from all substrates, except glutamine. The highest percent increase was obtained with alanine (64%), compared with 31-40% for glutamate, lactate, and glycerol. The T4 treatment induced increase in glucose synthesis by renal tubule fragments suggests that renal gluconeogenesis contributes to enhance glucose production in hyperthyroidism.