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Objective: To determine if baseline subgroups in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial can be identified for whom intensive compared with standard glycemia treatment had different effects on all-cause mortality.Research Design and Methods: Exploratory post hoc intention-to-treat comparisons were made between intensive and standard glycemia groups on all-cause mortality by subgroups defined by baseline characteristics.Results: There were few significant interactions between baseline characteristics and effects of intensive versus standard glycemia treatment on mortality: self-reported history of neuropathy (hazard ratio [HR] 1.95, 95% CI 1.41-2.69) versus no history of neuropathy (0.99, 0.79-1.26; P value for interaction 0.0008), higher A1C (A1C >8.5%: HR 1.64, 95% CI 1.22-2.22; A1C 7.5-8.4%: 1.00, 0.75-1.34; A1C <7.5%: 1.00, 0.67-1.50; P value for interaction 0.04), and aspirin use (HR 1.45, 95% CI 1.13-1.85, compared with 0.96, 0.72-1.27, in nonusers; P value for interaction 0.03).Conclusions: We found a remarkable similarity of effect from intensive compared with standard glycemia treatment on mortality across most baseline subgroups. No differential effect was found in subgroups defined by variables anticipated to have an interaction: age, duration of diabetes, and previous history of cardiovascular disease. The three baseline characteristics that defined subgroups for which there was a differential effect on mortality may help identify patients with type 2 diabetes at higher risk of mortality from intensive regimens for glycemic control. Further research is warranted. [ABSTRACT FROM AUTHOR]

La Clínica del Pueblo, a health education collaboration between the Maya Angelou Center for Health Equity at Wake Forest University School of Medicine and Qué Pasa Media, Inc., disseminates culturally appropriate health information to the North Carolina (NC) Latino community. The program includes a weekly radio show and corresponding newspaper column addressing four areas: childhood health, adult health, safety, and utilization. The radio show format includes a didactic presentation followed by a call-in question and answer period. Over 200 consecutive weeks of programming have been completed, averaging 11 calls per show. A Latino healthcare resource guide and hotline also provide resource information. Participant demographic information indicates that 50% of the target population comes from Mexico, 60% are women, and 70% of the community is younger than 38 years. There was an increase in the use of the media as a source of health information over the course of the project, from an initial 33% of respondents to 58% in the last survey. Listenership to La Clínica del Pueblo displayed a pronounced increase (18% initial survey to 55% in last survey, P < 0.05). We also observed a statistically significant increase in medical knowledge from initial survey to the last survey (P < 0.001). By multiple regression analysis, we identified 4 predictors of medical knowledge: order of surveys (1 < 3, P < 0.001), education level (P < 0.0001), female gender (P < 0.01) and radio listenership (P < 0.05). The first three variables predicted higher scores; however, radio listening recognition of our radio program was more common among individuals who had lower scores. In conclusion, La Clínica del Pueblo is a model for a novel approach that can reach the Latino community to improve medical knowledge and possibly affect health behaviors in a positive manner. [ABSTRACT FROM AUTHOR]

Erratic blood glucose levels can be a cause and consequence of delayed gastric emptying in patients with diabetes. It is unknown if better glycemic control increases risks of hypoglycemia or improves hemoglobin A1c levels and gastrointestinal symptoms in diabetic gastroparesis. This study investigated the safety and potential efficacy of continuous subcutaneous insulin infusion (CSII) and continuous glucose monitoring (CGM) in poorly controlled diabetes with gastroparesis. Forty-five type 1 or 2 patients with diabetes and gastroparesis and hemoglobin A1c >8% from the NIDDK Gastroparesis Consortium enrolled in a 24 week open-label pilot prospective study of CSII plus CGM. The primary safety outcome was combined numbers of mild, moderate, and severe hypoglycemic events at screening and 24 weeks treatment. Secondary outcomes included glycemic excursions on CGM, hemoglobin A1c, gastroparesis symptoms, quality-of-life, and liquid meal tolerance. Combined mild, moderate, and severe hypoglycemic events occurred similarly during the screening/run-in (1.9/week) versus treatment (2.2/week) phases with a relative risk of 1.18 (95% CI 0.85-1.64, P = 0.33). CGM time in hypoglycemia (<70 mg/dL) decreased from 3.9% to 1.8% (P<0.0001), time in euglycemia (70-180 mg/dL) increased from 44.0% to 52.0% (P = 0.02), time in severe hyperglycemia (>300 mg/dL) decreased from 14.2% to 7.0% (P = 0.005), and hemoglobin A1c decreased from 9.4±1.4% to 8.3±1.3% (P = 0.001) on CSII plus CGM. Symptom scores decreased from 29.3±7.1 to 21.9±10.2 with lower nausea/vomiting, fullness/early satiety, and bloating/distention scores (P≤0.001). Quality-of-life scores improved from 2.4±1.1 to 3.1±1.1 (P<0.0001) and volumes of liquid nutrient meals tolerated increased from 420±258 to 487±312 mL (P = 0.05) at 24 weeks. In conclusion, CSII plus CGM appeared to be safe with minimal risks of hypoglycemic events and associated improvements in glycemic control, gastroparesis symptoms, quality-of-life, and meal tolerance in patients with poorly controlled diabetes and gastroparesis. This study supports the safety, feasibility, and potential benefits of improving glycemic control in diabetic gastroparesis.

Gastroparesis is a complication of long-standing type 1 and type 2 diabetes mellitus. Symptoms associated with gastroparesis include early satiety, prolonged postprandial fullness, bloating, nausea and vomiting, and abdominal pain. Mortality is increased in patients with diabetic gastroparesis. A subset of patients with diabetic gastroparesis have pylorospasm that results in obstructive gastroparesis. Current treatment approaches include improving glucose control with insulin and prescribing antinauseant drugs, prokinetic agents, and gastric electric stimulation. Future directions include improved diet counseling based on gastric emptying rate, continuous insulin delivery systems with glucose sensor-augmented monitoring, and drugs for correcting gastric neural and electric abnormalities., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Hispanics in the United States represent diverse racial, ethnic, and socioeconomic groups, and manifest heterogeneous cardiovascular risks including diabetes. It is not known if there are residual differences in the control of diabetes among Hispanic groups given uniform access to diabetes care., Objective: To evaluate glucose control differences among Mexicans, Puerto Ricans, and Dominicans receiving substantial diabetes care and support in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial., Design: Secondary analysis of data from a randomized trial comparing two treatment strategies: intensive, targeting glycated hemoglobin below 6.0 %, and standard, targeting glycated hemoglobin between 7.0 % and 7.9 %., Participants: Seven hundred and sixteen Hispanic and 6066 non-Hispanic white participants were recruited from 77 clinical sites across the United States and Canada. There were 243 Mexicans, 199 Puerto Ricans, and 150 Dominicans; and 135 of these Hispanic groups were born in the United States., Main Measure: Glycated hemoglobin, Results: Compared to Puerto Ricans, Mexicans were more likely (HR=1.38, CI:0.90-2.10) and Dominicans as likely (HR=1.01, CI:0.66-1.54) to achieve glycated hemoglobin goal in the intensive arm. Participants born in the United States achieved glycated hemoglobin goal at a higher rate than those born elsewhere (HR=1.57, CI:0.99-2.51 in the intensive arm, HR=1.51, CI:0.95-2.43 in the standard arm). These differences were not statistically significant. In the intensive arm, Puerto Ricans (OR=0.47, CI:0.31-0.71), and Dominicans (OR=0.41, CI:0.26-0.66) were less likely than non-Hispanic whites to achieve glycated hemoglobin goal, whereas the difference between non-Hispanic whites and Mexicans was not statistically significant, (OR=0.66, CI:0.43-1.02)., Conclusions: Hispanic groups, given access to comprehensive diabetes care, differed from each other non-significantly and had a variable divergence from non-Hispanic whites in achieving intensive glycated hemoglobin goal. These differences, if confirmed, could be due to such factors as variable acculturation and functional health literacy levels that were not measured in the ACCORD trial, but should be further explored in future studies.

Objective: To examine the relation between insulin sensitivity and total and regional body fat in nonobese postmenopausal women., Design: Cross-sectional study., Setting: A clinical research center., Patient(s): Twenty-seven women in the early postmenopausal period, with a mean (+/-SD) age of 50.8 +/- 4.1 years, who had had their last menstrual period 6 months to 3 years before the study. None were taking hormone replacement therapy, and all had an FSH level of >35 mIU/mL, a body mass index of <30 kg/m2, and a waist circumference of <94 cm., Intervention(s): Computed tomography scans at the L4-5 vertebral disk space, dual-photon x-ray absorptiometry scans, and euglycemic hyperinsulinemic clamps were performed., Main Outcome Measure(s): Intraabdominal fat, subcutaneous abdominal fat, sagittal diameter, total body fat, percent body fat, and insulin sensitivity., Result(s): The natural log of insulin sensitivity correlated significantly with intraabdominal fat (r = -.39), subcutaneous fat (r = -.43), and sagittal diameter (r = -.48). After adjusting for total fat, sagittal diameter remained significantly related to insulin sensitivity., Conclusion(s): Central abdominal fat is inversely and independently related to insulin sensitivity after adjusting for total fat in women in the early postmenopausal period. Efforts to reduce either subcutaneous abdominal fat or intraabdominal fat should be helpful in reducing the risk of noninsulin-dependent diabetes mellitus in postmenopausal women.

The beta 3 subtype of adrenaline and noradrenaline receptors has been extensively characterized at structural and functional levels. Ligand binding and adenyl cyclase activation studies have helped to define their unique beta-adrenergic profile. Humans, other larger mammals, and rodents share most of the characteristic beta 3-adrenergic receptor properties, although obvious species-specific differences have been identified. Most studies in animal models have shown a distinct beta 3-adrenergic receptor activity that results in an increase in energy expenditure, decrease of fat mass (especially of intra-abdominal fat), and increased glucose disposal efficiency. It is of interest that mild weight increase was shown to develop in female but not male mice, in whom the beta 3-adrenergic receptor gene was disrupted. Recently, the incidence of a naturally occurring variant of the human beta 3-adrenergic receptor was shown to correlate with hereditary obesity in Pima Indians and Japanese individuals. In Western obese patients, this phenotype increased the capacity to gain weight and develop type 2 diabetes mellitus. Studies of humans with the Trp64Arg variant have shown controversial results. Many studies have failed to show any effect in heterozygous male subjects, and only modest effects in homozygous male subjects. In women, several studies have shown modest-to-significant effects regarding weight gain, intra-abdominal fat, and decreased insulin sensitivity in heterozygous and homozygous women. Other studies have failed to show any effect in heterozygous females. Disruptions in the activity of the beta 3-adrenergic receptor in the homozygous male and the heterozygous or homozygous female appear to have a profound effect in animal models, but a limited consequence in human physiology. Association with obesity or diabetes in humans is still controversial. This difference between animal and human models may be explained by the different quantity and distribution of metabolically active brown adipose tissue in the two.

There is controversy regarding the role of the Trp64Arg variant of the beta3-adrenergic receptor (beta3AR) gene in the pathogenesis of insulin resistance. The modest effect of the variant as well as differences in study design, gender, age, and genetic background may contribute to divergent results among investigations. Insulin sensitivity (euglycemic clamp and tracers) was measured in 13 obese women (57 +/- 6 yr old) heterozygous for the beta3AR variant and in 14 women (57 +/- 4 yr old) homozygous for the normal gene. Groups were matched for age, body composition, intraabdominal fat, sc abdominal fat, physical activity level, and aerobic capacity. Exogenous glucose infusion during the clamp was significantly lower (P = 0.03) in beta3AR heterozygotes (241 +/- 135 mg/min) vs. normal homozygotes (379 +/- 172 mg/min). Basal endogenous glucose production was not different (P = 0.20) between heterozygotes (175 +/- 27 mg/min) and normal homozygotes (164 +/- 14 mg/min). Endogenous glucose production during hyperinsulinemia was also not different (P = 0.22) between heterozygotes (77 +/- 57 mg/min) and normal homozygotes (56 +/- 16 mg/min). Total glucose disposal adjusted for residual endogenous glucose production was lower (P = 0.049) for heterozygotes (320 +/- 111 mg/min) than for normal homozygotes (441 +/- 183 mg/min). Our results suggest that obese postmenopausal women who are heterozygous for the Trp64Arg variant in the beta3AR gene have greater insulin resistance than age-, body composition-, and physical activity-matched women homozygous for the normal gene.

The rate of fat oxidation at rest decreases with age in women. The mechanisms for this decrease are not clear. Theoretically, a decrease in the availability of fatty acids could explain the decline in fat oxidation. In consequence, the in vivo rate of production of fatty acids as a proxy for lipolysis was measured in 21 healthy women. Eleven of the volunteers were elderly (> 65 years) and 10 were young (< 24 years), and all were characterized for body composition. The nonadjusted rate of delivery of fatty acids into the systemic circulation was similar among elderly and young individuals (609 +/- 80.3 v 597 +/- 69.9 mumol/min, respectively, P > .1). When lipolysis was adjusted for the differences in fat-free mass using analysis of covariance (ANCOVA), rates were slightly increased in the elderly group (626 +/- 80 mumol/min) and decreased in the young group (578 +/- 84 mumol/min), but remained nonstatistically significant. It is concluded that mechanisms other than lipolysis must explain the decrease of fat oxidation in aging women, i.e., a decrease in the capacity of muscle to oxidize fat and/or a decrease in its capacity for transport of long-chain fatty acids.

The hypothesis that exercise increases fat oxidation at rest independently of changes in energy balance, body composition, and/or lipolysis was tested in 21 volunteers. After a period of energy balance, volunteers were randomly allocated to one of four groups: control, overfed (OF), overfed and exercised (OF-EX), and exercised (EX). OF and OF-EX were overfed 50% excess of energy balance calories; OF-EX and EX spent 50% excess of energy balance calories during daily exercise sessions. Exercise increased fat oxidation at rest independently of dietary intake (OF-EX = + 22 +/- 2.4, EX = + 23 +/- 1.5 mg/min) and reduced carbohydrate oxidation (OF-EX = - 49 +/- 6.2, EX = - 46 +/- 5.4 mg/min). Volunteers in the OF group had an increase in carbohydrate oxidation (85 +/- 5.9 mg/min) and a decline in fat oxidation (- 33 +/- 1.4 mg/min). Protein oxidation did not change in any group. These changes occurred without a direct relation with changes in lipolysis and persisted even when expressed as a percentage or as an absolute equivalent of resting metabolic rate in calories. Thus exercise, independent of changes in energy intake and body composition and not related to changes in lipolysis, increases fat oxidation at rest, which may explain the beneficial effects of exercise in weight loss programs.

The present study tested the hypothesis that a decrease in basal fat oxidation in aging women is related to a loss of fat-free mass. Thirty-two nonsmoking women with a wide range of age (18-73 yr) were characterized for body composition (underwater weight), maximal aerobic capacity, and basal fat oxidation (indirect calorimetry). Results showed that fat oxidation was negatively correlated with age (r2 = 0.17, P = 0.017) but was positively correlated with the fat-free mass (r2 = 0.48, P < 0.0001) and with the level of aerobic fitness (maximal aerobic capacity) (r2 = 0.22, P = 0.007). Unexpectedly, fat oxidation had no relationship with fat mass (r2 = 0.07, P = 0.136). Partial correlation analysis showed that the decline in fat-free mass, and not the age or maximal O2 consumption, was the best single predictor of the decline in basal fat oxidation. These results support the theory that a decrease in fat oxidation with advancing age in healthy women is associated with a decrease in the fat-free mass and not age per se. Interventions that increase or preserve the quantity of fat-free mass (e.g., exercise training) may enhance fat oxidation and thus lessen the age-associated adiposity in women.

The impact of aerobic fitness level on the production and disposal of serum free fatty acids was investigated in 26 normal young volunteers. The fitness level was ascertained by history and confirmed by determination of maximal aerobic capacity. Energy expenditure and substrate oxidation at rest were measured with indirect calorimetry. Free fatty acid turnover was measured with an infusion of [14C]palmitic acid. All tests were done > or = 48 h after the last bout of exercise. The sedentary (SED) volunteers had higher rates of systemic delivery of fatty acids than aerobically fit (FIT) individuals (532 +/- 53.4 vs. 353 +/- 62.3 mumol/min; P = 0.05). This difference was accentuated when the values were normalized to fat-free mass (9.2 +/- 0.8 and 5.9 +/- 0.98 mumol.kg-1.min-1 for SED and FIT, respectively). Fatty acid oxidation was similar between FIT and SED volunteers in absolute numbers (209 +/- 25 vs. 202 +/- 21 mumol/min, respectively; NS) as well as when normalized to fat-free mass (3.8 +/- 0.9 vs. 3.6 +/- 1.4 mumol.kg-1.min-1, respectively; NS). In contrast, the nonoxidative disposal of serum fatty acids was higher in SED (330 +/- 46.1 mumol/min) than in FIT individuals (144 +/- 52 mumol/min; P = 0.026). Thus, the ratio of nonoxidative to oxidative disposal rates of fatty acids was higher in SED than in FIT individuals (1.65 +/- 0.29 vs. 0.75 +/- 0.17; P = 0.021). The data support the hypothesis that high aerobic fitness level is associated with a low rate of systemic delivery of fatty acids at rest. Nevertheless, subjects with high aerobic fitness levels have fat oxidation at the same rate as unfit individuals.

The quantitative contribution of hepatic glucose cycling to basal and glucagon-stimulated thermogenesis was investigated in seven normal healthy volunteers in whom energy expenditure (EE) was measured simultaneously with indirect calorimetry. Primed-constant infusions of 2-(2H1)-glucose and 6-6'-(2H2)-glucose were used to calculate hepatic glucose cycling. Gas chromatography/mass spectrometry was used to measure the plasma enrichment of isotopes. In response to hyperglucagonemia, basal EE increased an average of 7.1% +/- 2.3% (P < .05). This thermogenic effect of glucagon was completely blunted when insulin levels were increased sevenfold over the basal concentration. Hepatic glucose cycling comprised 15% +/- 4% of basal glucose turnover and increased more than 100% in response to isolated hyperglucagonemia. The increase in liver glucose cycling was observed also when serum insulin concentrations were increased sevenfold above baseline. Thus, we were able to induce dissociation of the activation of hepatic glucose cycling and the thermogenic response induced by hyperglucagonemia. From the quantitative point of view, the thermogenic cost of the cycles was less than 1% in both the basal and stimulated state. Thus, we concluded that hepatic glucose cycles play a quantitatively minor role in EE in man.

We studied the prevalence of non-insulin dependent diabetes (NIDDM) and hyperlipemia in older than 15 years old population in the city of San Luis Potosi and in a rural area 50 km north of this city. They are located in the state of San Luis Potosi in the central plateau of Mexico. A total of 1136 subjects were surveyed (645 males, 491 females). Weight and height were measured and the body mass index (BMI) calculated in all subjects. After a fasting capillary sample was obtained, 75 g of glucose were given and a second sample was taken 120 minutes later. The WHO recommendations for diagnosis of DM were used. The overall prevalence of DM was 10.0%: the lowest rate was for individuals in the rural area (0.9%) which contrasts with the 11% seen in the urban population (p 0.0001). In the urban subjects, the highest rates were observed in the very low income group (27.7%) whereas the low income group had a rate of 6.2%; the prevalence was 7.0, 7.7 and 18.2% in the medium, high medium and high socioeconomic groups. The prevalence was influenced by age, BMI, sex (males = 6.8% females = 14.3%) and socioeconomic status; hypercholesterolemia (> 200 mg/dL) was found in 16%. In conclusion, we have documented high rates of NIDDM in a mexican urban population with very high levels in the very poor which contrasts with the rural population.

The effects of ingesting a mixed-snack food (CB), fructose (FRU), or placebo (PBO) prior to exercise (70% peak VO2) on the metabolic response during and after cycle exercise were studied in eight normal healthy volunteers with a wide range of peak VO2 (30-70 cc.kg-1.min-1). The study was designed to minimize the impact of confounding factors by using various strategies. First, the volunteers were grouped in teams with stratification by peak VO2, and the tests were randomized by a Latin-square design. Second, subjects received two acclimation trials in the cycle ergometer to diminish the effect of learning experiences and allow them to get used to the room and equipment. In addition, financial incentives were offered for team and individual endurance times. The test meals were administered 30 min prior to the beginning of exercise, and the subjects exercised to exhaustion, which was defined with clear-cut endpoints. Gas and blood samples were taken at regular intervals before, during, and for 60 min after each exercise bout. CB and FRU induced higher pre-exercise glucose and insulin concentrations. Blood lactate increased 100% with FRU ingestion. Despite these differences; endurance time, substrate, and hormone concentrations as well as rates of substrate oxidation during exercise were identical among the three conditions. During the post-exercise recovery period, PBO was associated with a starvation-like pattern of substrate utilization in which lipid oxidation was 60% greater and carbohydrate oxidation 50% less than following either CB (75 +/- 11, 248 +/- 27 mg.min-1, P less than 0.05) or F ingestion (93 +/- 4, 221 +/- 14 mg.min-1).(ABSTRACT TRUNCATED AT 250 WORDS)