In vitro determination of normal and neoplastic human brain tissue optical properties using inverse adding-doubling.

To complement a project towards the development of real-time optical biopsy for brain tissue discrimination and surgical resection guidance, the optical properties of various brain tissues were measured in vitro and correlated to features within clinical diffuse reflectance tissue spectra measured in vivo. Reflectance and transmission spectra of in vitro brain tissue samples were measured with a single-integrating-sphere spectrometer for wavelengths 400-1300 nm and converted to absorption and reduced scattering spectra using an inverse adding-doubling technique. Optical property spectra were classified as deriving from white matter, grey matter or glioma tissue according to histopathologic diagnosis, and mean absorption and reduced scattering spectra were calculated for the three tissue categories. Absolute reduced scattering and absorption values and their relative differences between histopathological groups agreed with previously reported results with the exception that absorption coefficients were often overestimated, most likely due to biologic variability or unaccounted light loss during reflectance/transmission measurement. Absorption spectra for the three tissue classes were dominated by haemoglobin absorption below 600 nm and water absorption above 900 nm and generally determined the shape of corresponding clinical diffuse reflectance spectra. Reduced scattering spectral shapes followed the power curve predicted by the Rayleigh limit of Mie scattering theory. While tissue absorption governed the shape of clinical diffuse reflectance spectra, reduced scattering determined their relative emission intensities between the three tissue categories.

2-D motion estimation using two parallel receive beams.

We describe a method for estimating 2-D target motion using ultrasound. The method is based on previous ensemble tracking techniques, which required at least four parallel receive beams and 2-D pattern matching. In contrast, the method described requires only two parallel receive beams and 1-D pattern matching. Two 1-D searches are performed, one in each lateral direction. The direction yielding the best match indicates the lateral direction of motion. Interpolation provides sub-pixel magnitude resolution. We compared the two beam method with the four beam method using a translating speckle target at three different parallel beam steering angles and transducer angles of 0, 45, and 90 degrees. The largest differences were found at 90 degrees, where the two beam method was generally more accurate and precise than the four beam method and also less prone to directional errors at small translations. We also examined the performance of both methods in a laminar flow phantom. Results indicated that the two beam method was more accurate in measuring the flow angle when the flow velocity was small. Computer simulations supported the experimental findings. The poorer performance of the four beam method was attributed to differences in correlation among the parallel beams. Specifically, center beams 2 and 3 correlated better with each other than with the outer beams. Because the four beam method used a comparison of a kernel region in beam pair 2-3 with two different beam pairs 1-2 and 3-4, the 2-to-1 and 3-to-4 components of this comparison increased the incidence of directional errors, especially at small translations. The two beam method used a comparison between only two beams and so was not subject to this source of error. Finally, the two beam method did not require amplitude normalization, as was necessary for the four beam method, when the two beams were chosen symmetric to the transmit axis. We conclude that two beam ensemble tracking can accurately estimate motion using only two parallel receive beams.

Speckle tracking for multi-dimensional flow estimation.

Speckle tracking methods overcome the major limitations of current Doppler methods for flow imaging and quantification: angle dependence and aliasing. In this paper, we review the development of speckle tracking, with particular attention to the advantages and limitations of two-dimensional algorithms that use a single transducer aperture. Ensemble tracking, a recent speckle tracking method based upon parallel receive processing, is described. Experimental results with ensemble tracking indicate the ability to measure laminar flow in a phantom at a beam-vessel angle of 60 degrees, which had not been possible with previous 2D speckle tracking methods. Finally, important areas for future research in speckle tracking are briefly summarized.

Meeting American Diabetes Association guidelines in endocrinologist practice.

OBJECTIVE: To determine whether American Diabetes Association (ADA) guidelines can be met in the context of routine endocrinology practice. RESEARCH DESIGN AND METHODS: Charts were reviewed for a group of patients who were examined in 1998, followed for > or = 1 year, and had two or more visits during that year. Process measures and metabolic outcomes were studied for patients with type 2 diabetes, and glycemic control was assessed for patients with type 1 diabetes. RESULTS: A total of 121 patients with type 2 diabetes had a mean age of 63 years, a mean BMI of 31 kg/m2, and a mean duration of diabetes of 12 years. Many had comorbidities or complications: 80% had hypertension, 64% had hyperlipidemia, 78% had neuropathy, 22% had retinopathy, and 21% had albuminuria. Management of type 2 diabetic patients was complex: 38% used oral hypoglycemic agents alone (54% of these were using two or more agents), 31% used oral hypoglycemic agents and insulin, and 26% used insulin alone; 42% of patients taking insulin therapy injected insulin three or more times per day. Within 12 months, 74% of patients had dilated eye examinations, 70% had lipid profiles, and 55% had urine albumin screening. Of the patients, 87% had a foot examination at their last visit. Blood pressure levels averaged 133/72 mmHg, cholesterol levels averaged 4.63 mmol/l, triglyceride levels averaged 1.99 mmol/l, HDL cholesterol levels averaged 1.24 mmol/l, and LDL cholesterol levels averaged 2.61 mmol/l. Random blood glucose levels averaged 8.0 mmol/l, and HbAlc levels averaged 6.9 +/- 0.1%. A total of 87% of patients had HbAlc levels < or = 8.0%. A total of 30 patients with type 1 diabetes had mean age of 44 years, a mean BMI of 26 kg/m2, and a mean duration of diabetes of 20 years. All type 1 diabetic patients used insulin and averaged 3.4 injections a day; their average HbAlc level was 7.1 +/- 0.2%, and 80% had HbAlc levels < or = 8.0%. CONCLUSIONS: Although endocrinologists must manage patients with multifaceted problems, complex treatment regimens yield glycemic control levels comparable with the Diabetes Control and Complications Trial and allow ADA guidelines to be met in a routine practice setting.

Influence of diabetes mellitus on early and late outcome after coronary artery bypass grafting.

BACKGROUND: Diabetes mellitus is an established independent risk factor for significant morbidity and mortality after coronary artery bypass grafting. METHODS: The impact of diabetes on short- and longterm follow-up after coronary artery bypass grafting was studied by comparing the outcomes between 9,920 patients without diabetes mellitus and 2,278 patients with diabetes from 1978 to 1993. RESULTS: Compared with nondiabetic patients, the group with diabetes was older (62+/-10 years versus 60+/-10 years), comprised more women (31% versus 19%), had a greater incidence of hypertension (61% versus 44%) and previous myocardial infarction (51% versus 48%), had class III-IV angina more commonly (69% versus 63%), showed a higher incidence of congestive heart failure (11% versus 5%) or triple-vessel or left main disease (60% versus 50%), and had lower ejection fractions (0.54 versus 0.57) (all, p< or =0.05). Diabetic patients had a higher incidence of postoperative death (3.9% versus 1.6%) and stroke (2.9% versus 1.4%) (both, p< or =0.05), but not Q wave myocardial infarction (1.8% versus 2.9%). Diabetics had lower survival (5 years, 78% versus 88%; 10 years, 50% versus 71%; both, p< or =0.05) and lower freedom from percutaneous transluminal coronary angioplasty (5 years, 95% versus 96%; 10 years, 83% versus 86%; latter, p< or =0.05), but diabetics did not have lower freedom from either myocardial infarction (5-years, 92% versus 92%; 10-years, 80% versus 84%) or additional coronary artery bypass grafting (5-years, 98% versus 99%; 10-years, 90% versus 91%). Multivariate correlates of long-term mortality were diabetes, older age, reduced ejection fraction, hypertension, congestive heart failure, number of vessels diseased, and urgent or emergent operation. CONCLUSIONS: Diabetics have a worse hospital and longterm outcome after coronary artery bypass grafting. The increased risk in such patients can only partially be explained by other demographic characteristics.

Insulin-resistant diabetes mellitus in a black woman with ataxia-telangiectasia.

A 24-year-old woman with ataxia-telangiectasia had traumatic arthritis, elevated serum transaminase values, polyuria, polydipsia, and a serum glucose level of 575 mg/dL. A relatively high daily dose of insulin (2.8 U/kg) was required to achieve near normoglycemia. The fasting insulin concentration was elevated. During an insulin-modified frequently sampled intravenous glucose tolerance test, the first phase of insulin release in response to the administration of glucose was blunted. The insulin sensitivity was similar to that found in individuals with non-insulin-dependent diabetes mellitus. Insulin receptor antibodies were not detected in the serum. We conclude that insulin resistance and islet beta-cell dysfunction are characteristics of diabetes mellitus in ataxia-telangiectasia. Contrary to a previous report, our findings do not support a cause-and-effect relationship between insulin receptor antibodies and insulin resistance in this disorder.

Insulin resistance associated with maternally inherited diabetes and deafness.

Maternally inherited diabetes and deafness (MIDD) is a form of diabetes associated with mutation of mitochondrial DNA (mtDNA) that occurs in 1% to 2% of individuals with diabetes. Understanding the clinical course and abnormalities in insulin secretion and action in affected individuals should allow better understanding of how this genetic defect alter glucose metabolism. We report the clinical course of three individuals with mtDNA mutations and deafness. Subjects no. 1 and 2 had diabetes not yet requiring insulin therapy, and subject no. 3, the son of subject no. 2, had normal glucose tolerance. Defective oxidative phosphorylation (OXPHOS) based on OXPHOS enzymology of skeletal muscle biopsy of subjects no. 1 and 2 showed activity of less than 5% of the tolerance level in complex III for subject no. 1 and in complexes I, I + III, and IV for subject no. 2. Assessing insulin secretion using insulin response to intravenous glucose and insulin sensitivity based on minimal model analysis of an insulin-modified frequently sampled intravenous glucose tolerance test (FSIGT), first-phase insulin secretion was abnormal in subjects no. 1 and 2 and normal in subject no. 3 (AUC, 57, 93, and 1,235 pmol/L, respectively). In contrast, all three subjects had low insulin sensitivity indices (0.04, 0.14, and 0.27 x 10-4 x min/pmol/L, respectively). Subject no. 2, who underwent three FSIGT studies over a 16-month interval, showed transient improvement in insulin release in response to modification of diet and exercise (first-phase insulin AUC, 57 pmol/min v 287 pmol/min 10 months later; fasting insulin, 97 pmol/L v 237 pmol/L 10 months later), but by 16 months, first-phase insulin release and fasting insulin had decreased (AUC, 64 and 136 pmol/L, respectively) despite higher fasting glucose. We conclude that in our subjects with MIDD, insulin resistance is present and appears to precede defects in insulin release.

Diabetic ketoacidosis in obese African-Americans.

Our preliminary data indicate that 15% of African-American patients presenting with diabetic ketoacidosis (DKA) are obese. To determine underlying mechanisms, we analyzed the clinical characteristics and indexes of insulin secretion and insulin sensitivity in 35 obese patients with DKA, 22 obese patients with hyperglycemia, 10 lean patients with DKA, and 10 obese nondiabetic subjects. Studies were performed 1 day after resolution of DKA and after 12 weeks of follow-up. At presentation, both obese DKA and obese hyperglycemic patients had no detectable insulin response to intravenous glucose, but they did respond to glucagon administration. The acute insulin response (AIR) to glucagon in obese DKA patients (0.9 +/- 0.1 ng/ml, P < 0.01), but significantly greater than in lean patients with DKA (0.1 +/- 0.1 ng/ml, P < 0.01). After 12 weeks of follow-up, the AIR to glucose improved in both groups of obese diabetic patients but remained significantly lower than in nondiabetic control subjects (both P < 0.01). In contrast, the AIR to glucagon was not significantly different from that in obese control subjects. Insulin sensitivity was decreased in both groups of obese diabetic patients at presentation and improved after follow-up to levels similar to those in obese nondiabetic control subjects. Reactivity with islet cell antibodies was not detected in any of the patients. During follow-up, 25 of 35 obese DKA and 16 of 22 hyperglycemic patients were able to discontinue insulin therapy, with continued good metabolic control. Our results indicate that in African-Americans, obese patients with DKA represent a subset of type II diabetes.(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of diabetes mellitus on early and late outcome after percutaneous transluminal coronary angioplasty.

BACKGROUND: Although patients with diabetes mellitus constitute an important segment of the population undergoing coronary angioplasty, the outcome of these patients has not been well characterized. METHODS AND RESULTS: Data for 1133 diabetic and 9300 nondiabetic patients undergoing elective angioplasty from 1980 to 1990 were analyzed. Diabetics were older and had more cardiovascular comorbidity. Insulin-requiring (IR) diabetics had diabetes for a longer duration and worse renal and ventricular functions compared with non-IR subjects. Angiographic and clinical successes after angioplasty were high and similar in diabetics and nondiabetics. In-hospital major complications were infrequent (3%), with a trend toward higher death or myocardial infarction in IR diabetics. Five-year survival (89% versus 93%) and freedom from infarction (81% versus 89%) were lower, and bypass surgery and additional angioplasty were required more often in diabetics. In diabetics, only 36% survived free of infarction or additional revascularization compared with 53% of nondiabetics, with a marked attrition in the first year after angioplasty, when restenosis is most common. Multivariate correlates of decreased 5-year survival were older age, reduced ejection fraction, history of heart failure, multivessel disease, and diabetes. IR diabetics had worse long-term survival and infarction-free survival than non-IR diabetics. CONCLUSIONS: Coronary angioplasty in diabetics is associated with high success and low complication rates. Although long-term survival is acceptable, diabetics have a higher rate of infarction and a greater need for additional revascularization procedures, probably because of early restenosis and late progression of coronary disease. The most appropriate treatment for these patients remains to be determined.

Insulin resistance in obesity is associated with elevated basal lactate levels and diminished lactate appearance following intravenous glucose and insulin.

Lactate metabolism is altered in obesity. Increasing obesity is associated with increased blood lactate levels after an overnight fast. In contrast, we have recently shown a marked decrease in the capacity for acute lactate generation in obese subjects following an oral glucose load, which we postulated might be linked to altered insulin sensitivity. In the present study, we systematically analyzed the relationship between insulin sensitivity (the Sensitivity Index [SI] derived using the minimal model), body mass index (BMI), and glucose, insulin, and lactate levels in the basal state and following intravenous (IV) glucose and insulin administration in lean and obese subjects. The results showed that SI and BMI were inversely related, as expected. Insulin sensitivity was more tightly associated with glucose, insulin, and lactate levels (both basal and integrated) than obesity per se. A significant inverse relationship was found between SI and basal lactate levels (r = -.56). Moreover, a significant and positive relationship was found between SI and incremental lactate area under the curve (reflecting acute lactate production) (r = .41). In a multiple regression analysis to separate the independent effects of obesity (BMI) and insulin sensitivity, after adjusting for age, sex, and race, SI accounted for 34% of the variance in basal lactate and 24% of the variance in incremental lactate area. Obesity independently accounted for 10% of the variance in basal lactate and 11% of the variance in incremental lactate area, neither of which were statistically significant. We conclude that elevations in basal lactate are associated with the development of insulin resistance.(ABSTRACT TRUNCATED AT 250 WORDS)

A comparison of home glucose monitoring with determinations of hemoglobin A1c, total glycated hemoglobin, fructosamine, and random serum glucose in diabetic patients.

We compared four objective measures of glycemic control (fructosamine, total glycated hemoglobin, hemoglobin A1c, and random serum glucose) with home glucose monitoring records in 17 diabetic patients followed up prospectively for 4 months. There was good overall correlation between all of these objective measures and weekly mean capillary glucose values. However, considerable scatter was seen in the data such that none of the glycated protein measurements was an ideal predictor of home glucose values. For example, all markedly elevated home glucose levels (greater than 11.1 mmol/L) were associated with elevated glycated protein levels, but moderately high blood glucose levels (8.3 to 11.1 mmol/L) were associated with one or more normal glycated protein values in some patients. Similar correlations were obtained whether glycemia was estimated by 1-week or 6-week home averages. Random serum glucose level also correlated with average home glucose level; however, there was wide fluctuation within individual subjects. All three glycated protein measurements (hemoglobin A1c, glycated hemoglobin, and fructosamine) appear equally useful as a supplement to home glucose monitoring in the assessment of glycemic control. Of the three types of glycated protein assays, fructosamine, with its advantage of speed and simplicity, may offer a more cost-effective alternative.

Minimal model analysis of intravenous glucose tolerance test-derived insulin sensitivity in diabetic subjects.

Although minimal model analysis of frequently sampled iv glucose tolerance tests (FSIGTs) to measure insulin sensitivity is well recognized, application has been limited by the need for endogenous insulin secretion. In the present study we determined whether use of exogenous insulin could permit minimal model assessment of insulin sensitivity (SI) to be extended to diabetic subjects. Normal volunteers had separate FSIGT assessments supplemented with both tolbutamide and insulin to accelerate glucose disappearance, while diabetics had a FSIGT supplemented only with insulin. There was a strong and highly significant correlation between the two assessments in normal subjects (r = 0.87; P less than 0.001), and the rank order of SI generally was maintained with the two assessments over a 3-fold range of SI; however, insulin-determined SI was 16% lower (3.4 +/- 0.4 vs. 4.1 +/- 0.4 x 10(-4) min/microU.microL; P less than 0.01). Diabetic subjects had markedly lower insulin sensitivity than controls (SI = 0.61 +/- 0.16; P less than 0.0001). Across all subjects, the level of fasting serum glucose was correlated inversely with both insulin sensitivity (r = -0.62; P less than 0.05) and acute insulin responses (r = -0.72; P less than 0.02); however, insulin sensitivity in diabetic subjects with little insulin secretion (0.6 +/- 0.2) was comparable to insulin sensitivity in diabetic subjects with near-normal responses (0.6 +/- 0.3). In subjects with fasting hyperglycemia, there were significant correlations between insulin sensitivity and body mass index, percent fat mass, and waist/hip ratio (all P less than 0.03). Among all female subjects, there was also a strong correlation between insulin sensitivity and upper body obesity, as measured by waist/hip ratio (r = -0.68; P less than 0.02). Model parameters also permitted glucose uptake to be estimated in diabetic vs. normal subjects at comparable hyperglycemia (11.1 mmol/L). Total glucose uptake was decreased in diabetic subjects (5.2 +/- 0.8 vs. 12.7 +/- 1.7 mg/min.kg in normals; P less than 0.001), insulin-dependent glucose uptake was diminished to a greater extent (1.3 +/- 0.4 vs. 6.2 +/- 1.2) than noninsulin-independent glucose uptake (3.9 +/- 0.5 vs. 6.4 +/- 0.9; both P less than 0.02). Administration of insulin permits minimal model FSIGT analysis to be applied to diabetic as well as normal subjects, yielding information about both insulin- and noninsulin-mediated glucose uptake as well as insulin sensitivity and insulin secretion.

Prediction of glucose response to weight loss in patients with non-insulin-dependent diabetes mellitus.

Although diet therapy is considered the cornerstone of therapy for obese patients with non-insulin-dependent diabetes mellitus, losing weight is often difficult, and the plasma glucose concentration does not always improve after weight loss. We looked for predictors of improvement in plasma glucose levels after weight loss in 135 obese patients with non-insulin-dependent diabetes mellitus who had lost at least 9.1 kg of body weight. After weight loss there was a bimodal distribution of plasma glucose levels, allowing us to identify patients as "responders" or "nonresponders" according to whether a random plasma glucose level was above or below 10.0 mmol/L after a 9.1-kg weight loss. Fifty-five (41%) of 135 patients were responders (after a 9.1-kg weight loss, the mean +/- SEM plasma glucose level was 7.0 +/- 0.2 mmol/L). Many responders had improved plasma glucose levels after only slight weight loss. Eighty (59%) of 135 patients were nonresponders (after a 9.1-kg weight loss, the mean +/- SEM plasma glucose level was 18.3 +/- 0.6 mmol/L). Although the responder and nonresponder groups were comparable in age, sex distribution, plasma glucose levels, and body weight at initial presentation, improvement in the plasma glucose level after weight loss could be predicted by a plasma glucose level of 10.0 mmol/L or lower after 2.3-kg (62% positive predictive value) and 4.5-kg (79% positive predictive value) weight loss. We conclude that, in contrast to conventional teaching, many patients with non-insulin-dependent diabetes mellitus will not have any improvement in plasma glucose levels after a 9.1-kg weight loss. However, a substantial minority (approximately 40%) of obese patients with non-insulin-dependent diabetes mellitus have much lower plasma glucose levels with a weight loss of 9.1 kg or less. Although the plasma glucose response to weight loss cannot be forecast by initial clinical parameters, the success or failure of diet therapy can be predicted from the plasma glucose level after a weight loss of only 2.3 to 4.5 kg. Mild or moderately obese patients with non-insulin-dependent diabetes mellitus who remain hyperglycemic after a weight loss of 2.3 to 9.1 kg are unlikely to improve with further weight loss and should be considered for treatment with insulin or oral hypoglycemic agents.

Reversible impairment of gonadotropin secretion in critical illness. Observations in postmenopausal women.

Gonadotropin levels were measured in 65 postmenopausal women admitted to the intensive care unit. Sixteen patients (25%) were hypogonadotropic as measured by luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels of 5 IU/L or less, and only 20 patients (31%) were found to have gonadotropin levels within the expected postmenopausal range (greater than or equal to 30 IU/L). No significant differences in prolactin or free thyroxine levels were found, but the cortisol level was higher and the total thyroxine level lower in the hypogonadotropic group. The patients in the hypogonadotropic group also seemed more seriously ill, with a longer duration of hospitalization, an increased total number of days in the intensive care unit, an increased number of days in the intensive care unit before gonadotropin sampling, a higher incidence of parenteral hyperalimentation, lower serum albumin levels, and higher mortality. Stimulation of the gonadotropin-releasing hormone performed on 10 patients showed a blunted response in patients with baseline LH and FSH levels of 10 IU/L or less. Of 10 patients followed up sequentially, 6 showed a rise in gonadotropin levels that paralleled recovery, 1 died with low gonadotropin levels, and 3 continued to have low gonadotropin levels 17, 34, and 82 days, respectively, after initial screening. Critically ill postmenopausal women may exhibit a marked fall in gonadotropin, LH, and FSH levels. This disease in gonadotropin levels in response to illness is reversible and results from pituitary unresponsiveness to gonadorelin hydrochloride.