History's Future in the North End

http://deepblue.lib.umich.edu/bitstream/2027.42/110960/1/history_s_future_in_the_north_endred.pd

3-(4-Bromo­phenyl­sulfon­yl)-8-methyl-1,3-diaza­spiro­[4.5]decane-2,4-dione

The crystal structure of the title compound, C15H17BrN2O4S, is stabilized by inter­molecular N—H⋯O hydrogen bonds which link the mol­ecules into centrosymmetric dimers. The dihedral angle subtended by the 4-bromo­phenyl group with the mean plane passing through the hydantoin unit is 83.29 (5)°. The cyclo­hexyl group adopts an ideal chair conformation with the methyl group in an equatorial position

3-(4-Chloro­phenyl­sulfon­yl)-8-methyl-1,3-diaza­spiro­[4.5]decane-2,4-dione

In the title compound, C15H17ClN2O4S, the atoms in the hydantoin ring are coplanar (r.m.s. deviation = 0.006 Å). The crystal structure is stabilized by inter­molecular N—H⋯O hydrogen bonds which link the mol­ecules into centrosymmetric dimers. The dihedral angle subtended by the 4-chloro­phenyl group with the plane passing through the hydantoin unit is 82.98 (4)°. The cyclo­hexyl ring adopts an ideal chair conformation

Hostility, Race, and Glucose Metabolism in Nondiabetic Individuals

OBJECTIVE— The present study was designed to determine whether hostility is differentially related to measures of glucose metabolism in African-Americans and Caucasians. RESEARCH DESIGN AND METHODS— The relationship of hostility, as measured by a subset of the Cook-Medley hostility scale (CMHOST) inventory items, to various parameters of glucose metabolism were examined in a young, healthy sample of male and female African-American and Caucasian volunteers. Fasting blood samples were collected during an inpatient admission, at which time the CMHOST was also administered. RESULTS— In the entire sample, the CMHOST was found to be significantly correlated with fasting glucose and insulin sensitivity, as measured by the homeostatic model assessment (HOMA). However, the relationship of hostility to these parameters of glucose metabolism was different in African-American and Caucasian subjects. Hostility was significantly related to fasting glucose in African-Americans and to insulin sensitivity and fasting insulin in Caucasian subjects. The relationship of hostility to insulin sensitivity and fasting insulin was partially dependent on BMI in Caucasians, but the relationship of hostility to fasting glucose was unrelated to BMI in African-Americans. CONCLUSIONS— Our data suggest that the relationship of hostility to measures of glucose metabolism is mediated differently in these two ethnic groups. Therefore, hostility seems to be part of a constellation of risk-related behaviors related to BMI in Caucasians but independently related to fasting glucose in African-Americans

The effects of baseline characteristics, glycaemia treatment approach, and glycated haemoglobin concentration on the risk of severe hypoglycaemia: post hoc epidemiological analysis of the ACCORD study

Objectives To investigate potential determinants of severe hypoglycaemia, including baseline characteristics, in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial and the association of severe hypoglycaemia with levels of glycated haemoglobin (haemoglobin A1C) achieved during therapy

Effects of the Dietary Approaches to Stop Hypertension Diet Alone and in Combination With Exercise and Caloric Restriction on Insulin Sensitivity and Lipids

This study examined the effects of the Dietary Approaches to Stop Hypertension (DASH) diet on insulin sensitivity and lipids. In a randomized control trial, 144 overweight (body mass index 25–40) men (N= 47) and women (N= 97) with high blood pressure (130–159/85–99 mm Hg) were randomly assigned to either: (1) DASH diet alone (DASH-A); (2) DASH diet with aerobic exercise and caloric restriction (DASH-WM); or usual diet controls (UC). Body composition, fitness, insulin sensitivity, and fasting lipids were measured before and following 4 months of treatment. Insulin sensitivity was estimated based on glucose and insulin levels in the fasting state and after an oral glucose load. Participants in the DASH-WM condition lost weight (−8.7 [95% CI = −2.0, −9.7] kg,), and exhibited a significant increase in aerobic capacity, while the DASH-A and UC participants maintained their weight (−0.3 [95% CI = −1.2, 0.5] kg and +0.9 [95% CI = 0.0, 1.7] kg, respectively) and had no improvement in exercise capacity. DASH-WM demonstrated lower glucose levels following the oral glucose load, improved insulin sensitivity, and lower total cholesterol and triglycerides compared to both DASH-A and UC, and lower fasting glucose and low-density lipoprotein cholesterol compared to UC; DASH-A participants generally did not differ from UC in these measures. Combining the DASH diet with exercise and weight loss resulted in significant improvements in insulin sensitivity and lipids. Despite clinically significant reductions in blood pressure, the DASH diet alone, without caloric restriction or exercise, resulted in minimal improvements in insulin sensitivity or lipids

Canagliflozin, dapagliflozin and empagliflozin monotherapy for treating type 2 diabetes: systematic review and economic evaluation

Background: Most people with type 2 diabetes are overweight, so initial treatment is aimed at reducing weight and increasing physical activity. Even modest weight loss can improve control of blood glucose. If drug treatment is necessary, the drug of first choice is metformin. However, some people cannot tolerate metformin, which causes diarrhoea in about 10%, and it cannot be used in people with renal impairment. This review appraises three of the newest class of drugs for monotherapy when metformin cannot be used, the sodium–glucose co-transporter 2 (SGLT2) inhibitors. Objective: To review the clinical effectiveness and cost-effectiveness of dapagliflozin (Farxiga, Bristol-Myers Squibb, Luton, UK), canagliflozin (Invokana, Janssen, High Wycombe, UK) and empagliflozin (Jardiance, Merck & Co., Darmstadt, Germany), in monotherapy in people who cannot take metformin. Sources: MEDLINE (1946 to February 2015) and EMBASE (1974 to February 2015) for randomised controlled trials lasting 24 weeks or more. For adverse events, a wider range of studies was used. Three manufacturers provided submissions. Methods: Systematic review and economic evaluation. A network meta-analysis was carried out involving the three SGLT2 inhibitors and key comparators. Critical appraisal of submissions from three manufacturers. Results: We included three trials of dapagliflozin and two each for canagliflozin and empagliflozin. The trials were of good quality. The canagliflozin and dapagliflozin trials compared them with placebo, but the two empagliflozin trials included active comparators. All three drugs were shown to be effective in improving glycaemic control, promoting weight loss and lowering blood pressure (BP). Limitations: There were no head-to-head trials of the different flozins, and no long-term data on cardiovascular outcomes in this group of patients. Most trials were against placebo. The trials were done in patient groups that were not always comparable, for example in baseline glycated haemoglobin or body mass index. Data on elderly patients were lacking. Conclusions: Dapagliflozin, canagliflozin and empagliflozin are effective in improving glycaemic control, with added benefits of some reductions in BP and weight. Adverse effects are urinary and genital tract infections in a small proportion of users. In monotherapy, the three drugs do not appear cost-effective compared with gliclazide or pioglitazone, but may be competitive against sitagliptin (Januvia, Boehringer Ingelheim, Bracknell, UK). Funding: The National Institute for Health Research Health Technology Assessment programme