Moderate‐To‐vigorous physical activity is associated with decreases in body mass index from ages 9 to 15 years

Objective:

The purpose of this study is to determine whether time spent in objectively measured physical activity is associated with change in body mass index (BMI) from ages 9 to 15.

Design and Methods:

The participants were enrolled in the National Institute of Child Health and Human Development Study of Early Child Care and Youth Development (n = 938). At ages 9, 11, 12, and 15 the time spent in moderate‐to‐vigorous physical activity (MVPA) was objectively measured, and BMI was calculated (kg/m²). Longitudinal quantile regression was used to analyze the data. The 10th, 25th, 50th, 75th, and 90th BMI percentiles were modeled as the dependent variables with age and MVPA (h/day) modeled as predictors. Adjustment was also made for gender, race, sleep, healthy eating score, maternal education, and sedentary behavior.

Results:

A negative association between MVPA and change in BMI was observed at the 90th BMI percentile (?3.57, 95% CI ?5.15 to ?1.99 kg/m² per hour of MVPA). The negative association between time spent in MVPA and change in BMI was progressively weaker toward the 10th BMI percentile (?0.27, 95% CI ?0.62 to 0.07 kg/m² per hour of MVPA). The associations remained similar after adjusting for the covariates, and when the analyses were stratified by gender.

Conclusion:

Time spent in MVPA was negatively associated with change in BMI from age 9 to 15. The association was strongest at the upper tail of the BMI distribution, and increasing time spent in MVPA could help reduce the prevalence of childhood obesity.

     

Patterning of children's sedentary time at and away from school

Objective:

Sedentary behavior in children is positively associated with an increased risk of both obesity and insulin resistance. Children spend a considerable portion of their awake time in sedentary behavior; however, the pattern of accumulation is not known. Thus the objective of this study was to describe the patterning of sedentary behavior of children at and away from school.

Design and Methods:

The patterns of sedentary time in a sample of 53 children (28 girls) aged 10‐12 years during school‐term time were examined. Children wore an accelerometer for 1 week. Total sedentary time, prolonged sequences (bouts) of sedentary time, and frequency of active interruptions to sedentary were examined on school days and weekends and within school time and non‐school time on school days.

Results:

The data did not support our hypothesis that children accumulated more sedentary time on school days when compared with weekend days (mean [SD]: 64.4% [5.3] vs. 64.9% [9.0], P = 0.686). However, when comparing school time with non‐school time on school days, children accumulated more sedentary time at school (66.8% [7.3] vs. 62.4% [5.2], P < 0.001) and spent more time at school in sustained sedentary sequences, that is, uninterrupted sedentary time for 30 min or more (75.6 min [45.8] vs. 45.0 min [26.8], P < 0.002). The children also recorded less breaks per sedentary hour within school time when compared with non‐school time (8.9 h^?1 vs. 10.2 h^?1, P < 0.001).

Conclusion:

Reducing total sedentary time spent both in and out of school remains an important challenge. Interrupting sedentary time more often in the “working” (school) day could also reap important musculoskeletal and metabolic health rewards for children.

     

Plasma stearoyl‐CoA desaturase indices: Association with lifestyle,diet, and body composition

Objective:

Stearoyl‐coenzyme A desaturase‐1 (SCD1) is a key enzyme in fatty acid and energy metabolism. Increased hepatic SCD1 activity is associated with obesity and obesity‐related diseases. We examined the relations of two plasma SCD activity indices (16:1n‐7/16:0, 18:1n‐9/18:0) with body composition, and the association of lifestyle and dietary variables with the plasma SCD indices.

Design and Methods:

This population‐based, cross‐sectional study of 2021 elderly (71–74 y) men and women from the Hordaland Health Study in Western Norway was conducted using a validated food frequency questionnaire, body composition measurements by dual‐energy X‐ray absorptiometry and determination of the plasma fatty acid profile.

Results:

In multivariate regression analyses, plasma SCD indices were positively associated with BMI and body fat (P < 0.001 for both). From the 2.5th to 97.5th percentiles of plasma SCD‐16 and SCD‐18 indices, fat mass differed by about 8 kg and 5 kg, respectively. Intake of polyunsaturated fatty acids were negatively associated with SCD‐16 (partial r = ?0.30) and SCD‐18 (partial r = ?0.24) (P < 0.001 for both). Alcohol intake was positively associated with SCD‐16 (partial r = 0.26) and SCD‐18 (partial r = 0.16) (P < 0.001 for both), whereas coffee consumption and physical activity were inversely associated with SCD‐16 (P = 0.026 and P = 0.006, respectively) and SCD‐18 (P = 0.001 and P = 0.022, respectively).

Conclusions:

In this elderly population, plasma markers of SCD1 activity are associated with increased adiposity. Furthermore, modifiable dietary habits and lifestyle are associated with plasma SCD indices. These results suggest that SCD1 activity may be a promising target for weight control.

     

Cortisol,obesity, and the metabolic syndrome: A cross‐sectional study of obese subjects and review of the literature

Objective:

Circulating cortisol and psychosocial stress may contribute to the pathogenesis of obesity and metabolic syndrome (MS). To evaluate these relationships, a cross‐sectional study of 369 overweight and obese subjects and 60 healthy volunteers was performed and reviewed the previous literature.

Design and Methods:

Overweight and obese subjects had at least two other features of Cushing's syndrome. They underwent measurements representing cortisol dynamics (24 h urine cortisol excretion (UFC), bedtime salivary cortisol, 1 mg dexamethasone suppression test) and metabolic parameters (BMI, blood pressure (BP); fasting serum triglycerides, HDL, insulin, and glucose). Subjects also completed the Perceived Stress Scale (PSS). UFC, salivary cortisol, and weight from 60 healthy volunteers were analyzed.

Results:

No subject had Cushing's syndrome. UFC and dexamethasone responses were not associated with BMI or weight. However, salivary cortisol showed a trend to increase as BMI increased (P < 0.0001), and correlated with waist circumference (WC) in men (r_s = 0.28, P = 0.02) and systolic BP in women (r_s = 0.24, P = 0.0008). Post‐dexamethasone cortisol levels were weak to moderately correlated with fasting insulin (r_s = ?0.31, P = 0.01) and HOMA‐IR (r_s = ?0.31, P = 0.01) in men and systolic (r_s = 0.18, P = 0.02) and diastolic BP (r_s = 0.20, P = 0.009) in women. PSS results were higher in obese subjects than controls, but were not associated with cortisol or metabolic parameters. As expected, WC correlated with fasting insulin, HOMA‐IR, and systolic BP (adjusted for BMI and gender; P < 0.01). Literature showed inconsistent relationships between cortisol and metabolic parameters.

Conclusion:

Taken together, these data do not support a strong relationship between systemic cortisol or stress and obesity or MS.

     

A clinical model of obesity treatment is more effective in preschoolers and Spanish speaking families

Objective:

Preschool and minority children have not been well represented in obesity treatment studies. This analysis of clinical obesity treatment was carried out within a diverse population of children 2‐12 years to identify demographic characteristics associated with successful treatment.

Design and Methods:

A medical record review captured BMI and demographics for children 2‐12 years who began treatment during a 42‐month period (n = 479). Associations of body mass index z‐score (BMI‐Z) change with child and family demographics were examined with logistic regression and time‐to‐event analysis.

Results:

Treatment led to a mean BMI‐Z decrease of 0.18. Half of children with follow‐up (n = 273) exceeded the a priori cut‐off for successful treatment of ?0.1 BMI‐Z. Preschoolers and children of Spanish‐speakers were more likely to succeed, (Adjusted OR: 5.8 [95% CI: 2.7‐12.2] and 2.3 [95% CI: 1.1, 4.9]). The hazard ratio for treatment failure was 3.7 [95% CI: 2.1, 6.8] for children starting treatment at 6‐12 years compared to preschoolers, adjusted for other demographics.

Conclusions:

This mode of treatment was more likely to succeed among children treated before school age and among children whose parents spoke only Spanish. Screening and treatment for obesity in preschoolers and Hispanic immigrant families deserve further prospective study.

     

Arterial stiffness,lifestyle intervention and a low‐calorie diet in morbidly obese patients—A nonrandomized clinical trial

Objective:

Arterial stiffness is an independent predictor of cardiovascular morbidity and mortality. This study aimed to compare the 7‐week effect of a low‐calorie diet (LCD) and an intensive lifestyle intervention program (ILI) on arterial stiffness in morbidly obese individuals.

Design and Methods:

Nonrandomized clinical trial. The LCD provided 900 kcal/day, and participants in the LCD group were instructed to maintain their habitual physical activity level. The ILI included two 90‐min supervised training sessions 3 days a week at moderate to high intensity (4‐8 METs) and a caloric restriction of 1000 kcal/day.

Results:

A total of 179 individuals completed the study, 88 (56 women) in the ILI group and 91 (57 women) in the LCD group. High‐fidelity applanation tonometry (Millar^®, Sphygmocor^®) was used to measure carotid‐femoral pulse wave velocity (PWV). After adjustment for relevant confounders, the ILI group had a significantly greater reduction in PWV than the LCD group; ?0.4 (?0.6, ?0.1) m/s, P = 0.004. When compared to the LCD group, the ILI group showed a larger reduction in systolic and diastolic blood pressure ?5 (?9, ?1) and ?5 (?7, ?2) mmHg, P = 0.038 and P ≤ 0.001 respectively, whereas no difference was observed regarding pulse pressure, P = 0.661. No significant differences between groups were found regarding the loss of fat mass, P = 0.259, but the loss of muscle mass was larger in the LCD group, 0.8 (0.5, 1.1) kg, P ≤ 0.001.

Conclusion:

Despite the limitations of a nonrandomized design, our findings indicate that for morbidly obese individuals a moderate caloric restriction combined with aerobic physical exercise is associated with a greater decline in PWV than a LCD alone.

     

Measurements of total and regional body composition in preschool children: A comparison of MRI,DXA, and anthropometric data

Objective:

There are clear sex differences in the distribution of visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) in adults, with males having more VAT and less SAT than females. This study assessed whether these differences between the sexes were already present in preschool children. It also evaluated which measures of body composition were most appropriate for assessing abdominal obesity in this age group.

Design and Methods:

One‐hundred and five children (57 boys and 48 girls) participated in the study. Body composition was measured using dual‐energy X‐ray absorptiometry (DXA). Weight, height, and waist circumference (WC) were also recorded. Magnetic resonance imaging (MRI) of the entire abdomen using sixteen 10‐mm‐thick T₁‐weighted slices was performed in a subgroup of 48 children (30 boys and 18 girls); SAT and VAT volumes were measured using semiautomated segmentation.

Results:

Boys had significantly more VAT than girls (0.17 versus 0.10 l, P < 0.001). Results showed that VAT correlated significantly with all measurements of anthropometry (P < 0.01) after adjusting for SAT and for total fat mass measured with DXA. The mean limits of agreement between DXA and MRI regarding truncal FM were calculated to be ?11.4 (range ?17.8 to ?3.6), using a Bland–Altman plot.

Conclusion:

Sex differences in adipose tissue distribution are apparent at an early age. MRI is the best method with which to study abdominal fat distribution in young children.

     

Meta‐analysis of the association between body mass index and health‐related quality of life among adults,assessed by the SF‐36

Objective:

Obesity is associated with impaired overall health‐related quality of life but individual studies suggest the relationship may differ for mental and physical quality of life. A systematic review using Medline, Embase, PsycINFO and ISI Web of Knowledge, and random effects meta‐analysis was undertaken.

Design and Methods:

Studies were included in the meta‐analysis if they were conducted on adults (defined as age >16 years), reported an overall physical and mental component score of the SF‐36, and, or both. Heterogeneity was assessed using I² statistics and publication and small study biases using funnel plots and Egger's test. Between‐study heterogeneity was explored using meta‐regression.

Results:

Eight eligible studies provided 42 estimates of effect size, based on 43,086 study participants. Adults with higher than normal body mass index had significantly reduced physical quality of life with a clear dose‐response relationship across all categories. Among class III obese adults, the score was reduced by 9.72 points (95% Confidence Interval 7.24, 12.20, P < 0.001). Mental quality of life was also significantly reduced among class III obese (?1.75, 95% confidence interval ?3.33, ?0.16, P = 0.031), but was not significantly different among obese (class I and class II) individuals, and was significantly increased among overweight adults (0.42, 95% confidence interval 0.17, 0.67, P = 0.001), compared to normal weight individuals. Heterogeneity was high in some categories, but there was no significant publication or small study bias.

Conclusions:

Different patterns were observed for physical and mental HRQoL, but both were impaired in obese individuals. This meta‐analysis provides further evidence on the impact of obesity on both aspects of health‐related quality of life.

     

Associations of testosterone and sex hormone binding globulin with adipose tissue hormones in midlife women

Objective:

Regulators of adipose tissue hormones remain incompletely understood, but may include sex hormones. As adipose tissue hormones have been shown to contribute to numerous metabolic and cardiovascular disorders, understanding their regulation in midlife women is of clinical importance. Therefore, we assessed the associations between testosterone (T) and sex hormone binding globulin (SHBG) with leptin, high molecular weight (HMW) adiponectin, and the soluble form of the leptin receptor (sOB‐R) in healthy midlife women.

Design and Methods:

Cross‐sectional analyses were performed using data from 1,881 midlife women (average age 52.6 (±2.7) years) attending the sixth Annual follow‐up visit of the multiethnic Study of Women's Health Across the Nation.

Results:

T was weakly negatively associated with both HMW adiponectin and sOB‐R (r = ?0.12 and r = ?0.10, respectively; P < 0.001 for both), and positively associated with leptin (r = 0.17; P < 0.001). SHBG was more strongly and positively associated with both HMW adiponectin and sOB‐R (r = 0.29 and r = 0.24, respectively; P < 0.001 for both), and more strongly and negatively associated with leptin (r = ?0.27; P < 0.001). Adjustment for fat mass, insulin resistance, or waist circumference only partially diminished associations with HMW adiponectin and sOB‐R, but attenuated associations with leptin. In conclusion, in these midlife women, lower SHBG values, and to a lesser extent, higher T levels, were associated with lower, or less favorable, levels of adiponectin and sOB‐R, independent of fat mass.

Conclusions:

These data suggest that variation in these adipose hormones resulting from lower SHBG levels, and possibly, though less likely, greater androgenicity, may contribute to susceptibility for metabolic and cardiovascular outcomes during midlife in women.

     

Psychosocial predictors of 4‐year BMI change in overweight and obese children in primary care

Objective:

This study aimed to determine whether (( 1 ) ) initial and/or (( 2 ) ) changes in psychosocial functioning predict body mass index (BMI) z‐score change over 4 years in overweight/mildly obese 5‐ to 9‐year old children presenting to primary care.

Design and Methods:

Eligible participants (n = 258) were overweight/mildly obese children (IOTF criteria) recruited into the LEAP2 trial (ISRCTN52511065) from 3,958 children visiting general practitioners in Melbourne, Australia from May 2005 to July 2006. Predictors were change scores calculated from repeated measures of parent‐ and child‐reported child health‐related quality of life (PedsQL) and self‐esteem; child‐reported desire to be thinner; and parent‐reported child weight concern. Outcome was measured BMI z‐score change from baseline to 4 years.

Results:

The 189 respondents (61% female; 73% retention) showed little mean change in BMI z‐score (?0.08) but wide variation (standard deviation 0.50, range ?1.32 to 1.20). Only one baseline measure (better parent‐reported PedsQL School Functioning) predicted improving BMI z‐score. However, parents and children consistently reported that changes in psychosocial functioning (i.e., PedsQL Social and Global Self‐esteem) were inversely related to BMI z‐score change scores. The strongest predictors of decreases in BMI z‐scores were changes in child‐reported body‐image variables, i.e., improvements in Physical Appearance Self‐esteem (β =0.40, 95% CI ?0.98 to ?0.15, P < 0.01) and declines in Desire to be Thinner (β = 0.33, 95% CI 0.04 to 0.23, P < 0.01).

Conclusions:

At presentation to primary care, it seems unlikely that targeting the psychosocial factors measured in this study would influence BMI z‐score change in overweight/mildly obese children. Subsequent change in psychosocial well‐being covaries with BMI z‐score change and may have important adolescent ramifications; the causal directions for these associations require further research.

     

High‐normal tsh values in obesity: Is it insulin resistance or adipose tissue's guilt?

Objective:

Clinical evidences reported subclinical alterations of thyroid function in obesity, although the relationship between thyroid status and obesity remains unclear. We cross‐sectionally investigated the influence of metabolic features on hypothalamic–pituitary–thyroid axis in obesity.

Design and Methods:

We enrolled 60 euthyroid subjects with no history of type 2 diabetes mellitus and assessed the relationship of thyroid function with insulin resistance, measured using euglycemic clamp, and abdominal fat volume, quantified by computed tomography scan (CT scan). Thyroid stimulating hormone (TSH) correlated with BMI (r = 0.46; P = 0.02), both visceral (r = 0.58; P = 0.02) and subcutaneous adipose tissue volumes (r = 0.43; P = 0.03) and insulin resistance (inverse relationship with insulin sensitivity–glucose uptake: r = ?0.40; P = 0.04).

Results:

After performing multivariate regression, visceral adipose tissue volume was found to be the most powerful predictor of TSH (β = 3.05; P = 0.01), whereas glucose uptake, high‐density lipoprotein (HDL) cholesterol, low‐density lipoprotein (LDL) cholesterol, subcutaneous adipose tissue volume, and triglycerides were not. To further confirm the hypothesis that high‐normal TSH values could be dependent on adipose tissue, and not on insulin resistance, we restricted our analyses to moderately obese subjects' BMI ranging 30‐35 kg/m². This subgroup was then divided as insulin resistant and insulin sensitive according to the glucose uptake (≤ or >5 mg·kg^?1·min^?1, respectively). We did not find any statistical difference in TSH (insulin resistant: 1.62 ± 0.65 µU/ml vs. insulin sensitive: 1.46 ± 0.48; P = not significant) and BMI (insulin resistant: 32.2 ± 1.6 kg/m² vs. insulin sensitive: 32.4 ± 1.4; P = not significant), thus confirming absence of correlation between thyroid function and insulin sensitivity per se.

Conclusion:

Our study suggests that the increase in visceral adipose tissue is the best predictor of TSH concentration in obesity, independently from the eventual concurrent presence of insulin resistance.

     

Effect of dietary composition of weight loss diets on high‐sensitivity c‐reactive protein: The Randomized POUNDS LOST trial

Objective:

Overweight and obesity are associated with increased high‐sensitivity C‐reactive protein (hsCRP) levels. The purpose of this study was to determine if weight loss diets differing in fat, protein, or carbohydrate composition differentially reduce hsCRP.

Design and Methods:

POUNDS (preventing overweight using novel dietary strategies) LOST was a 2‐year trial of overweight and obese adults randomly allocated to one of four weight loss diets with targeted percentages of energy derived from fat, protein, and carbohydrates (20, 15, 65%; 20, 25, 55%; 40, 15, 45%; 40, 25, 35%, respectively). hsCRP was measured at baseline, 6, and 24 months among 710 participants, and adiposity as measured by dual X‐ray absorptiometry (N = 340) or abdominal computed tomography (N = 126) was correlated with hsCRP change.

Results:

At 6 months, hsCRP was reduced in all trial participants by ?24.7% (Interquartile range (IQR) +7%, ?50%), weight by ?6.7% (IQR ?3%, ?11%), and waist circumference by ?6.0% (IQR ?3%, ?10%) (all P < 0.002), with no significant differences according to dietary composition. The percent change in hsCRP at 6 and 24 months correlated modestly with change in weight, waist circumference, fasting insulin, fasting glucose, HOMA, and most lipid levels. Reductions in hsCRP persisted despite ～ 50% regain of weight by 24 months. The percent change in hsCRP at 24 months significantly correlated with changes in total body fat (r = 0.42), total abdominal adiposity (r = 0.52), subcutaneous abdominal adiposity (r = 0.52), visceral adiposity (r = 0.47), and hepatic tissue density (r = ?0.34) (all P < 0.0006).

Conclusion:

Weight loss decreased hsCRP by similar magnitude, irrespective of dietary composition. Clinicians concerned about inflammation and cardiovascular risk should recommend weight loss diets most likely to succeed for their patients.

     

Combining behavioral weight loss treatment and a commercial program: A randomized clinical trial

Objective:

To test the hypothesis that a novel weight loss approach that combined the fundamental components of professionally delivered behavioral weight loss (BWL) treatment with the existing Weight Watchers (WW) program would produce better weight losses than WW alone no differences were expected between the novel treatment and BWL alone.

Design and Methods:

Participants were 141 overweight and obese adults (90% women, 67% non‐White, mean age = 49.7 ± 9.2 years, mean body mass index = 36.2 ± 5.5 kg/m²) randomly assigned to 48 weeks of BWL, 48 weeks of WW, or 12 weeks of BWL followed by 36 weeks of WW [combined treatment (CT)]. Assessments were conducted at baseline and weeks 12, 24, and 48, with weight change as the primary outcome.

Results:

Linear mixed model analysis showed that 24‐week weight losses did not differ significantly between treatment groups; however, weight losses at 48 weeks were greater in the WW group (M = ?6.0 kg, standard error (SE) = 0.8) compared with the CT group (M = ?3.6 kg, SE = 0.8; P = 0.032), with BWL not significantly different from either (M = ?5.4 kg, SE = 0.8). Further, a greater proportion of WW participants lost 10% of baseline weight by 48 weeks compared with BWL or CT (36.7%, 13.0%, and 15.2%, respectively, P < 0.05).

Conclusion:

This study shows that the WW program can produce clinically meaningful weight losses and provides no evidence that adding brief BWL to the WW program improves outcome.

     

A randomized,phase 3 trial of naltrexone SR/bupropion SR on weight and obesity‐related risk factors (COR‐II)

Objective:

To examine the effects of naltrexone/bupropion (NB) combination therapy on weight and weight‐related risk factors in overweight and obese participants.

Design and Methods:

CONTRAVE Obesity Research‐II (COR‐II) was a double‐blind, placebo‐controlled study of 1,496 obese (BMI 30‐45 kg/m²) or overweight (27‐45 kg/m² with dyslipidemia and/or hypertension) participants randomized 2:1 to combined naltrexone sustained‐release (SR) (32 mg/day) plus bupropion SR (360 mg/day) (NB32) or placebo for up to 56 weeks. The co‐primary endpoints were percent weight change and proportion achieving ≥5% weight loss at week 28.

Results:

Significantly (P < 0.001) greater weight loss was observed with NB32 versus placebo at week 28 (?6.5% vs. ?1.9%) and week 56 (?6.4% vs. ?1.2%). More NB32‐treated participants (P < 0.001) experienced ≥5% weight loss versus placebo at week 28 (55.6% vs. 17.5%) and week 56 (50.5% vs. 17.1%). NB32 produced greater improvements in various cardiometabolic risk markers, participant‐reported weight‐related quality of life, and control of eating. The most common adverse event with NB was nausea, which was generally mild to moderate and transient. NB was not associated with increased events of depression or suicidality versus placebo.

Conclusion:

NB represents a novel pharmacological approach to the treatment of obesity, and may become a valuable new therapeutic option.

     

Serum hemorphin‐7 levels are decreased in obesity

Objective:

Hemorphin peptides exhibit biological activities that interfere with the endorphin system, the inflammatory response, and blood‐pressure control. VV‐hemorphin‐7 and LVV‐hemorphin‐7 peptides exert a hypotensive effect, in particular, by inhibiting the renin–angiotensin system. Furthermore, levels of circulating hemorphin‐7 peptides have been found to be decreased in diseases such as type 1 and type 2 diabetes.

Design and Methods:

Because type 2 diabetes and obesity share common features, such as insulin resistance, microinflammation, high glomerular‐filtration rate (GFR), and cardiovascular risk, we evaluated serum VV‐hemorphin‐7 like immunoreactivity (VVH7‐i.r.) levels, using an enzyme‐linked immunosorbent assay method, on a group of 54 obese subjects without diabetes or hypertension, compared with a group of 33 healthy normal‐weight subjects.

Results:

Circulating VVH7‐i.r. levels were significantly decreased in the obese group compared with the control group (1.98 ± 0.19 vs. 4.86 ± 0.54 µmol/l, respectively, P < 0.01), and a significant negative correlation between VVH7‐i.r. and diastolic blood pressure (DBP) was found in obese patients (r = ?0.35, P = 0.011). There was no significant correlation between VVH7‐i.r. level and insulin resistance, metabolic syndrome, or GFR.

Conclusions:

The decreased serum hemorphin‐7 found in obese subjects, as in diabetes, may contribute to the development of hypertension and to the cardiovascular risk associated with these metabolic diseases.

     

Effects of taspoglutide on glycemic control and body weight in obese patients with type 2 diabetes (T‐emerge 7 study)

Objective:

Therapies that lower blood glucose and provide weight loss may provide meaningful benefits for obese patients with type 2 diabetes mellitus (T2DM). This study assessed the efficacy of taspoglutide compared with placebo on glycemic control and weight in obese patients with T2DM inadequately controlled with metformin monotherapy.

Design and Methods:

In a 24‐week, randomized, double‐blind, placebo‐controlled, multicenter trial, obese adults with T2DM were randomized (1:1) to weekly subcutaneous taspoglutide 20 mg (10 mg for first 4 weeks) (n = 154) or placebo (n = 151) for 24 weeks. Efficacy measures included hemoglobin A1c (HbA1c) levels, body weight, percentage of patients achieving HbA1c ≤6.5 and ≤7.0%, and fasting plasma glucose (FPG). Adverse events (AEs) were assessed.

Results:

Mean baseline HbA1c was 7.55% and mean baseline BMI was 36.7 kg/m². HbA1c reductions from baseline were significantly greater with taspoglutide than placebo (least square mean [LSMean], ?0.81% vs. ?0.09%; P < 0.0001). Weight loss at week 24 was significantly greater with taspoglutide than placebo (LSMean, ?3.16 vs. ?1.85 kg; P < 0.01). In the taspoglutide and placebo groups, target HbA1c levels (≤6.5%) were achieved by 49 and 16% of patients, respectively, while 72 and 36% achieved HbA1c levels ≤7%. Decreases in FPG were significantly greater with taspoglutide than placebo (?23.59 vs. 0.09 mg/dl; P < 0.0001). Nausea and vomiting were the most common AEs associated with taspoglutide, but tended to be transient and generally mild or moderate.

Conclusions:

In obese patients with T2DM, once‐weekly taspoglutide provided the combined benefits of glycemic control and weight loss.

     

Lifestyle intervention and/or statins for the reduction of C‐reactive protein in type 2 diabetes: From the look AHEAD study

Objective:

Cardiovascular risk remains high despite statin use. Overweight/obese diabetic persons usually have normal/low LDL‐cholesterol but high C‐reactive protein (CRP) levels. We aimed to examine the effects of intensive lifestyle intervention for weight loss (ILI) on CRP levels in overweight/obese diabetic individuals by statin use.

Design and Methods:

Look AHEAD was a randomized trial in overweight/obese type 2 diabetic individuals testing whether ILI would reduce cardiovascular mortality, when compared to usual care. CRP changes in 1,431 participants with biomarker levels, who remained on or off statin treatment for 1 year, were evaluated.

Results:

The reduction in CRP levels with ILI at 1 year in men and women on statins was ?44.9 and ?42.3%, respectively, compared to ?13.7 and ?21.0% for those on statins and usual care (P < 0.0001). At 1 year, median CRP levels were: 1.8 mg L^?1 in participants randomized to ILI on statin therapy; 2.6 mg L^?1 for those on statins randomized to usual care and 2.9 mg L^?1 for participants not on statins but randomized to ILI. Weight loss was associated with 1‐year CRP reduction (P < 0.0001) in statin and nonstatin users.

Conclusions:

Our findings suggest that in overweight/obese diabetic persons, ILI and statin therapy may have substantial additive anti‐inflammatory benefits.

     

Effect of the mediterranean diet with and without weight loss on markers of inflammation in men with metabolic syndrome

Objective:

Intervention studies on the Mediterranean Diet (MedDiet) have often led to weight loss, which may have contributed to the purported anti‐inflammatory effects of the MedDiet. To investigate the impact of the MedDiet consumed under controlled feeding conditions before (?WL) and after weight loss (+WL) on markers of inflammation in men with metabolic syndrome (MetS).

Design and Methods:

Subjects (N = 26, male, 24–65 years) with MetS first consumed a North American control diet for 5 weeks followed by a MedDiet for 5 weeks both in isocaloric feeding conditions. After a 20‐week weight loss period in free‐living conditions (10 ± 3% reduction in body weight, P < 0.01), participants consumed the MedDiet again under isocaloric‐controlled feeding condition for 5 weeks.

Results:

MedDiet ? WL significantly reduced plasma C‐reactive protein (CRP) concentrations (?26.1%, P = 0.02) and an arbitrary inflammatory score (?9.9%, P = 0.01) that included CRP, interleukin‐6 (IL‐6), IL‐18, and tumor necrosis factor‐α (TNF‐α) compared with the control diet. The MedDiet + WL significantly reduced plasma IL‐6 (?20.7%) and IL‐18 (?15.6%, both P ≤ 0.02) concentrations compared with the control diet but had no further significant impact on plasma CRP concentration. Participants with a reduction in waist circumference ≥8.5 cm after MedDiet + WL showed significantly greater reductions in inflammation markers than those with a change in waist circumference <8.5 cm.

Conclusions:

Thus, consuming MedDiet even in the absence of weight loss significantly reduces inflammation. However, the degree of waist circumference reduction with weight loss magnifies the impact of the MedDiet on other markers of inflammation associated with MetS in men.

     

Liver fat and SHBG affect insulin resistance in midlife women: The Study of Women's Health Across the Nation (SWAN)

Objective:

The liver is an insulin‐responsive organ that contributes significantly to both whole body insulin sensitivity and availability of sex steroids through the production of sex hormone binding globulin (SHBG). Our objective was to explore whether lower SHBG was associated with ectopic liver fat and mediated its effect on insulin resistance in The Study of Women's Health Across the Nation (SWAN).

Design and Methods:

A subset of midlife African American and Caucasian women from SWAN (n = 208; 50.9 ± 0.18 yrs; 71% Caucasian) had computed tomography scans to quantify visceral, subcutaneous and liver fat. Blood samples were collected and assayed for hormonal and metabolic markers.

Results:

The cohort, while overweight, was generally healthy, and both liver fat and SHBG were unaffected by menopausal stage or race. Both higher liver fat and lower SHBG levels were significantly associated with higher insulin concentrations after adjustment for adiposity (r = ?0.25, P < 0.001 and r = ?0.18, P = 0.01). SHBG and liver fat had additive effects on insulin concentrations such that women with the lowest SHBG and the highest fat levels had the highest values (interaction P = 0.09). The association between SHBG and insulin was more apparent among women with fattier livers. SHBG and liver fat appear to have independent effects on insulin levels as adjustment for each other did not diminish the strength of either association (P = 0.023 and 0.001 respectively).

Conclusion:

These results confirmed the strong independent associations between increased liver fat and decreased SHBG with increased metabolic risk in midlife women. Further these data underscore the need for additional research into the role of liver fat in modifying SHBG's influence on insulin levels.

     

Central adiposity and other anthropometric factors in relation to risk of macrosomia in an african american population

Objective:

Previous studies have consistently identified maternal obesity and gestational weight gain (GWG) as risk factors for macrosomia, but little is known about the effects of central adiposity and body fat distribution. Using self‐reported data from the Black Women's Health Study (BWHS), a large follow‐up study of US black women, we examined the risk of macrosomia in relation to prepregnancy waist circumference, prepregnancy waist‐to‐hip ratio (WHR), prepregnancy BMI, and GWG.

Design and Methods:

During 1995–2003, BWHS participants ages 21–44 years delivered 6,687 full‐term singleton births (gestational age >37 weeks). We compared mothers of 691 infants weighing ≥4,000 g with mothers of 5,996 infants weighing <4,000 g. Generalized estimating equation models (GEE) that accounted for more than one birth per mother were used to estimate multivariable odds ratios (OR) and 95% confidence intervals (CI).

Results:

Independent of prepregnancy BMI, prepregnancy waist circumference was positively associated with risk of macrosomia (OR = 1.58, 95% CI: 1.07–2.32, for ≥35.0 vs. <27.0 inches (≥88.9 vs. <68.6 cm); P trend = 0.04). As expected, prepregnancy BMI was also positively associated with macrosomia (OR = 1.74, 95% CI: 1.25–2.41 for BMI ≥35.0 vs. 18.5–24.9 kg m^?2). GWG above the amount recommended by the 2009 Institute of Medicine report was associated with an increased risk of macrosomia and the association was present in each category of prepregnancy BMI (18.5–24.9, 25.0–29.9, and ≥30.0 kg m^?2; P trend <0.001).

Conclusions:

Our data suggest that overall obesity, high GWG, and high waist circumference are independent risk factors for macrosomia among US black women.