Pharmacological treatment of insulin resistance at two different stages in the evolution of type 2 diabetes: impact on glucose tolerance and beta-cell function

The purpose of this study was to compare the impact of treating insulin resistance with a thiazolidinedione drug before vs. at the onset of diabetes on glucose levels and beta-cell function.Nondiabetic Hispanic women of Mexican or Central American descent with prior gestational diabetes mellitus (GDM) were randomized to troglitazone (early intervention), 400 mg/d, or placebo (later intervention). Women who developed diabetes were placed on open-label troglitazone. Glucose tolerance, insulin resistance, and beta-cell function were measured at randomization, at the diagnosis of diabetes, and 8 months post trial to determine the long-term impact of the two treatment strategies on glucose levels and beta-cell function. During a mean follow-up of 4.3 yr between baseline and posttrial tests, glucose tolerance (oral glucose tolerance test glucose area, P = 0.04) and insulin resistance (MINMOD SI, P = 0.02) worsened more in women randomized to late intervention (n = 69) than to early intervention (n = 57). Insulin secretion (acute insulin response in the iv glucose tolerance test, P = 0.09) and beta-cell compensation for insulin resistance (disposition index, P = 0.07) also tended to worsen more in the late intervention group. Among women in the late intervention group who developed diabetes, oral glucose tolerance test glucose area (P = 0.0001) and beta-cell function (P < or = 0.04) deteriorated significantly during development of diabetes on placebo and then did not change significantly (P > 0.50) during treatment with troglitazone and posttreatment washout. In high-risk Hispanic women, amelioration of insulin resistance can stabilize glycemia at the time diabetes develops. These findings highlight the role of insulin resistance in the genesis of progressive beta-cell dysfunction during the evolution of type 2 diabetes.     

Reproducibility of T1 and T2 relaxation times calculated from routine MR imaging sequences: phantom study

Measurement of T1 and T2 relaxation times has been sought as one fundamental way to characterize tissue. Relaxation times can be calculated from routine spin-echo (SE) imaging sequences using two distinct repetition times (TRs), each with two SE samplings of signal intensity. Previous reports have quantified relaxation times without discussing the variation in their measurements. By imaging a phantom containing different samples with known T1 and T2 relaxation times on three separate occasions, the variation in relaxation time measurements inherent in different routine imaging sequences was studied. For the present study a more complete and accurate equation was used to calculate T1 values. The variation in T1 and T2 relaxation times for samples with relaxation times similar to solid tissue was 2%-4%. The amount of variability in calculated relaxation times was found to be dependent on the magnitude of the relaxation times themselves. However, the mean values were independent of the imaging sequences used to calculate the relaxation times. No significant differences were seen between left-to-right or section-to-section position within the same study or between studies performed on different occasions. The variability in the calculated T1 was dependent on the pair of TR sequences used to calculate T1. Samples with long T1 and T2 relaxation times, similar to many body fluids, had much larger variability. A computer simulation of measurement error was created to explain these results. This study indicates that properly performed routine imaging studies do yield reproducible T1 and T2 measurements.     

Response of pancreatic beta-cells to improved insulin sensitivity in women at high risk for type 2 diabetes

The purpose of this study was to examine the response of pancreatic beta-cells to changes in insulin sensitivity in women at high risk for type 2 diabetes. Oral glucose tolerance tests (OGTTs) and frequently sampled intravenous glucose tolerance tests (FSIGTs) were conducted on Latino women with impaired glucose tolerance and a history of gestational diabetes before and after 12 weeks of treatment with 400 mg/day troglitazone (n = 13) or placebo (n = 12). Insulin sensitivity was assessed by minimal model analysis, and beta-cell insulin release was assessed as acute insulin responses to glucose (AIRg) and tolbutamide (AIRt) during FSIGTs and as the 30-min incremental insulin response (30-min dINS) during OGTTs. Beta-cell compensation for insulin resistance was assessed as the product (disposition index) of minimal model insulin sensitivity and each of the 3 measures of beta-cell insulin release. In the placebo group, there was no significant change in insulin sensitivity or in any measure of insulin release, beta-cell compensation for insulin resistance, or glucose tolerance. Troglitazone treatment resulted in a significant increase in insulin sensitivity, as reported previously. In response, AIRg did not change significantly, so that the disposition index for AIRg increased significantly from baseline (P = 0.004) and compared with placebo (P = 0.02). AIRt (P = 0.001) and 30-min dINS (P = 0.02) fell with improved insulin sensitivity during troglitazone treatment, so that the disposition index for each of these measures of beta-cell function did not change significantly from baseline (P > 0.20) or compared with placebo (P > 0.3). Minimal model analysis revealed that 89% of the change from baseline in insulin sensitivity during troglitazone treatment was accounted for by lowered plasma insulin concentrations. Neither oral nor intravenous glucose tolerance changed significantly from baseline or compared with placebo during troglitazone treatment. The predominant response of beta-cells to improved insulin sensitivity in women at high risk for type 2 diabetes was a reduction in insulin release to maintain nearly constant glucose tolerance.     

Communication networks of medication management in an ambulatory care setting

Background

Systems approaches in healthcare address complexities of care related to medication safety. Adverse drug events can be prevented by communication between providers. Thus, methods that depict the structures and processes of communications are foundational for prevention efforts. Social network analysis is a methodology applied in healthcare settings to describe and quantify communication patterns. Knowledge of the structures and processes surrounding medication management communications will be useful to explain and intervene on related quality or safety outcomes.

Neuroendocrine regulation of plasma angiotensinogen.

In previous studies we found that plasma angiotensinogen levels were reduced by lesions of the hypothalamic paraventricular nuclei. To determine if the decrease was caused by decreased secretion of hormones that normally stimulate angiotensinogen secretion by the liver, we correlated the changes in plasma angiotensinogen produced by paraventricular lesions with changes in plasma LH, ACTH, and thyroid hormones; compared the changes in plasma angiotensinogen and other hormones to those produced by hypophysectomy; and determined the effects of treatment with ACTH and T4 in animals with paraventricular lesions. In male Sprague-Dawley rats, bilateral lesions destroying more than 50% of the paraventricular nuclei decreased plasma angiotensinogen to 787 +/- 52 ng angiotensin-I/ml in 7 days compared to 1576 +/- 142 ng angiotensin-I/ml in sham-operated controls. Plasma T3 and T4 were also reduced, whereas there were no statistically significant changes in plasma ACTH or LH. Hypophysectomy produced a comparable decline in plasma angiotensinogen and thyroid hormone levels. Daily administration of a single dose of ACTH had no effect on plasma angiotensinogen in rats with paraventricular lesions, but T4 treatment restored plasma angiotensinogen to normal levels. The data indicate that the decline in circulating angiotensinogen produced by lesions of the paraventricular nuclei is caused by the decrease in the secretion of thyroid hormones produced by these lesions. They also demonstrate that in addition to regulating circulating renin via the sympathetic nervous system, the brain has an effect on circulating angiotensinogen via neuroendocrine control of thyroid function.     

Antenatal diagnosis of placenta percreta with planned in situ retention and methotrexate therapy in a woman infected with HIV.

Placenta percreta is a rare obstetric condition associated with potentially life-threatening hemorrhage. Diagnosis in advance of delivery permits a planned delivery and preparation for blood transfusions and planned Cesarean hysterectomy, which is the common treatment. We report a case of placenta percreta in an HIV-positive patient which was diagnosed in the second trimester using conventional and extended field of view ultrasound imaging and color Doppler. At 36 weeks the infant was delivered by Cesarean section and the placenta was left in situ. Postoperatively the patient was treated with methotrexate. Four weeks later, the patient delivered the placenta spontaneously. Early or late postpartum hemorrhage did not occur and postoperative recovery was uneventful.