To examine whether the initial benefit of weight loss on obstructive sleep apnea (OSA) severity at 1 year is maintained at 4 years.
Randomized controlled trial with follow-up at 1, 2, and 4 years.
4 ...Look AHEAD clinical centers.
Two hundred sixty-four obese adults with type 2 diabetes and OSA.
Intensive lifestyle intervention with a behavioral weight loss program or diabetes support and education.
Change in apnea-hypopnea index on polysomnogram.
The intensive lifestyle intervention group's mean weight loss was 10.7 ± 0.7 (standard error), 7.4 ± 0.7, and 5.2 ± 0.7 kg at 1, 2, and 4 years respectively, compared to a less than 1-kg weight loss for the control group at each time (P < 0.001). Apnea-hypopnea index difference between groups was 9.7 ± 2.0, 8.0 ± 2.0, and 7.7 ± 2.3 events/h at 1, 2 and 4 years respectively (P < 0.001). Change in apnea-hypopnea index over time was related to the amount of weight loss (P < 0.0001) and intervention, independent of weight loss (P = 0.001). Remission of OSA at 4 years was 5 times more common with intensive lifestyle intervention (20.7%) than diabetes support and education (3.6%).
Among obese adults with type 2 diabetes and OSA, intensive lifestyle intervention produced greater reductions in weight and apnea-hypopnea index over a 4 year period than did diabetes support and education. Beneficial effects of intensive lifestyle intervention on apneahypopnea index at 1 year persisted at 4 years, despite an almost 50% weight regain. Effect of intensive lifestyle intervention on apnea-hypopnea index was largely, but not entirely, due to weight loss.
Summary
The aim of this study was to determine if an intensive lifestyle intervention (ILI) reduces the severity of obstructive sleep apnea (OSA) in rapid‐eye movement (REM) sleep, and to determine ...if longitudinal changes in glycaemic control are related to changes in OSA severity during REM sleep over a 4‐year follow‐up. This was a randomized controlled trial including 264 overweight/obese adults with type 2 diabetes (T2D) and OSA. Participants were randomized to an ILI targeted to weight loss or a diabetes support and education (DSE) control group. Measures included anthropometry, apnea–hypopnea index (AHI) during REM sleep (REM‐AHI) and non‐REM sleep (NREM‐AHI) and glycated haemoglobin (HbA1c) at baseline and year 1, year 2 and year 4 follow‐ups. Mean baseline values of REM‐AHI were significantly higher than NREM‐AHI in both groups. Both REM‐AHI and NREM‐AHI were reduced significantly more in ILI versus DSE, but these differences were attenuated slightly after adjustment for weight changes. Repeated‐measure mixed‐model analyses including data to year 4 demonstrated that changes in HbA1c were related significantly to changes in weight, but not to changes in REM‐AHI and NREM‐AHI. Compared to control, the ILI reduced REM‐AHI and NREM‐AHI during the 4‐year follow‐up. Weight, as opposed to REM‐AHI and NREM‐AHI, was related to changes in HbA1c. The findings imply that weight loss from a lifestyle intervention is more important than reductions in AHI for improving glycaemic control in T2D patients with OSA.
Gastric bypass surgery (GBP), in addition to weight loss, results in dramatic remission of type 2 diabetes (T2DM). The mechanisms by which this remission occurs are unclear. Besides weight loss and ...caloric restriction, the changes in gut hormones that occur after GBP are increasingly gaining recognition as key players in glucose control. Incretins are gut peptides that stimulate insulin secretion postprandially; the levels of these hormones, particularly glucagon-like peptide-1, increase after GBP in response to nutrient stimulation. Whether these changes are causal to changes in glucose homeostasis remain to be determined. The purpose of this review is to assess the evidence on incretin changes and T2DM remission after GBP, and the possible mechanisms by which these changes occur. Our goals are to provide a thorough update on this field of research so that recommendations for future research and criteria for bariatric surgery can be evaluated.
We examined the association of the Diabetes Prevention Program (DPP) intervention arms (lifestyle intervention, metformin, and placebo) with cognition in the Diabetes Prevention Program Outcomes ...Study (DPPOS). We also examined metformin use, incident type 2 diabetes, and glycemia as exposures.
The DPP lasted 2.8 years, followed by a 13-month bridge to DPPOS. Cognition was assessed in DPPOS years 8 and 10 (12 and 14 years after randomization) with the Spanish English Verbal Learning Test (SEVLT), letter fluency and animal fluency tests, Digit Symbol Substitution Test (DSST), and a composite cognitive score.
A total of 2,280 participants (749 lifestyle, 776 metformin, and 755 placebo) aged 63.1 ± 10.7 years underwent cognitive assessments; 67.7% women, 54.6% non-Hispanic white, 20.7% non-Hispanic black, 14.6% Hispanic, 5.5% American Indian, and 4.6% Asian; 26.6% were homozygous or heterozygous for APOE-ε4. At the time of cognitive assessment, type 2 diabetes was higher in the placebo group (57.9%;
< 0.001) compared with lifestyle (47.0%) and metformin (50.4%). Metformin exposure was higher in the metformin group (8.72 years;
< 0.001) compared with placebo (1.43 years) and lifestyle (0.96 years). There were no differences in cognition across intervention arms. Type 2 diabetes was not related to cognition, but higher glycated hemoglobin at year 8 was related to worse cognition after confounder adjustment. Cumulative metformin exposure was not related to cognition.
Exposure to intensive lifestyle intervention or metformin was not related to cognition among DPPOS participants. Higher glycemia was related to worse cognitive performance. Metformin seemed cognitively safe among DPPOS participants.
Summary
Background
LIFT (Lifestyle Intervention for Two) trial found that intervening in women with overweight and obesity through promoting healthy diet and physical activity to control gestational ...weight gain (GWG) resulted in neonates with greater weight, lean mass and head circumference and similar fat mass at birth. Whether these neonate outcomes are sustained at 1‐year was the focus of this investigation.
Methods
Measures included body composition by PEA POD air displacement plethysmography (ADP) and Echo Infant quantitative magnetic resonance (QMR) and head circumference at birth (n = 169), 14 (n = 136) and 54 weeks (n = 137). Differences in fat and lean mass between lifestyle intervention (LI) and Usual care (UC) groups were examined using ANCOVA adjusting for maternal age and BMI, GWG, offspring sex and age.
Results
Compared to UC, LI infants had similar weight (112 ± 131 g; P = .40), fat mass (14 ± 80 g; P = .86), lean mass (100 ± 63 g; P = .12) at 14 weeks and similar weight (168 ± 183 g; P = .36), fat mass (148 ± 124 g; P = .24), lean mass (117 ± 92 g; P = .21) at 54 weeks. Head circumference was greater in LI at 54 weeks (0.46 ± 2.1 cm P = .03).
Conclusions
Greater lean mass observed at birth in LI offspring was not sustained at 14 and 54 weeks, whereas the greater head circumference in LI offspring persisted at 54 weeks.
There is marked heterogeneity in the response to weight loss interventions with regards to weight loss amount and metabolic improvement. We sought to identify biomarkers predictive of type 2 diabetes ...remission and amount of weight loss in individuals with severe obesity enrolled in the Longitudinal Assessment of Bariatric Surgery (LABS) and the Look AHEAD (Action for Health in Diabetes) studies. Targeted mass spectrometry-based profiling of 135 metabolites was performed in pre-intervention blood samples using a nested design for diabetes remission over five years (n = 93 LABS, n = 80 Look AHEAD; n = 87 remitters), and for extremes of weight loss at five years (n = 151 LABS; n = 75 with high weight loss). Principal components analysis (PCA) was used for dimensionality reduction, with PCA-derived metabolite factors tested for association with both diabetes remission and weight loss. Metabolic markers were tested for incremental improvement to clinical models, including the DiaRem score. Two metabolite factors were associated with diabetes remission: one primarily composed of branched chain amino acids (BCAA) and tyrosine (odds ratio (95% confidence interval) OR (95% CI) = 1.4 1.0-1.9, p = 0.045), and one with betaine and choline (OR 95% CI = 0.7 0.5-0.9, p = 0.02).These results were not significant after adjustment for multiple tests. Inclusion of these two factors in clinical models yielded modest improvements in model fit and performance: in a constructed clinical model, the C-statistic improved from 0.87 to 0.90 (p = 0.02), while the net reclassification index showed improvement in prediction compared to the DiaRem score (NRI = 0.26, p = 0.0013). No metabolite factors associated with weight loss at five years. Baseline levels of metabolites in the BCAA and trimethylamine-N-oxide (TMAO)-microbiome-related pathways are independently and incrementally associated with sustained diabetes remission after weight loss interventions in individuals with severe obesity. These metabolites could serve as clinically useful biomarkers to identify individuals who will benefit the most from weight loss interventions.
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.
Abstract
Context
The effects of physiological improvements on cognitive function among persons with type 2 diabetes mellitus (T2DM) are not fully understood.
Objective
To determine whether ...improvements in physiological markers (body weight, blood sugar control, and physical activity) during intensive lifestyle intervention (ILI) are associated with enhancements in cognitive function in older adults with T2DM.
Design
Multisite randomized controlled trial.
Setting
Academic research centers.
Patients or Other Participants
Participants were aged 45–76 years, with T2DM.
Intervention
The Action for Health in Diabetes (Look AHEAD) study, a randomized, controlled clinical trial of ILI.
Main Outcome Measure
Two to 3 cognitive assessments were collected from 1089 participants, the first and last occurring a mean (standard deviation) of 8.6 (1.0) and 11.5 (0.7) years after enrollment.
Results
Greater improvement in blood sugar control was associated with better cognitive scores (fasting glucose and Rey Auditory Verbal Learning Test AVLT: P = 0.0148; fasting glucose and Digit Symbol Coding (DSC): P = 0.0360; HbA1C and DSC: P = 0.0477); but weight loss had mixed associations with cognitive scores (greater body mass index BMI reduction and worse AVLT overall: P = 0.0053; and greater BMI reduction and better DSC scores among those overweight but not obese at baseline: P = 0.010). Associations were strongest among those who were overweight (not obese) at baseline, and among those with a history of cardiovascular disease (CVD) at baseline.
Conclusions
Improvements in glycemic control, but not necessarily weight status, during ILI may be associated with better subsequent cognitive performance. These associations may differ by adiposity and CVD history.
Obesity and type 2 diabetes Maggio, Carol A; Pi-Sunyer, F Xavier
Endocrinology and metabolism clinics of North America,
12/2003, Letnik:
32, Številka:
4
Journal Article
Recenzirano
The increasing prevalence of obesity is accompanied by an increasing prevalence of type 2 diabetes. Obesity not only increases the risk of developing type 2 diabetes but also compounds its health ...risks and complicates its management. The health benefits of weight loss and the efficacy of current weight loss strategies in obese persons with type 2 diabetes are evaluated. In addition, the article reviews the results of lifestyle intervention trials designed to reduce conversion to type 2 diabetes in at-risk individuals.
To characterize the relationships among long-term improvements in peripheral insulin sensitivity (glucose disposal rate GDR), fasting glucose, and free fatty acids (FFAs) and concomitant changes in ...weight and adipose tissue mass and distribution induced by lifestyle intervention in obese individuals with type 2 diabetes.
We measured GDR, fasting glucose, and FFAs during a euglycemic clamp and adipose tissue mass and distribution, organ fat, and adipocyte size by dual-energy X-ray absorptiometry, CT scan, and adipose tissue biopsy in 26 men and 32 women in the Look-AHEAD trial before and after 1 year of diet and exercise aimed at weight loss.
Weight and fasting glucose decreased significantly (P < 0.0001) and significantly more in men than in women (-12 vs. -8% and -16 vs. -7%, respectively; P < 0.05), while FFAs during hyperinsulinemia decreased and GDR increased significantly (P < 0.00001) and similarly in both sexes (-53 vs. -41% and 63 vs. 43%; P = NS). Men achieved a more favorable fat distribution by losing more from upper compared with lower and from deeper compared with superficial adipose tissue depots (P < 0.01). Decreases in weight and adipose tissue mass predicted improvements in GDR but not in fasting glucose or fasting FFAs; however, decreases in FFAs during hyperinsulinemia significantly determined GDR improvements. Hepatic fat was the only regional fat measure whose change contributed independently to changes in metabolic variables.
Patients with type 2 diabetes undergoing a 1-year lifestyle intervention had significant improvements in GDR, fasting glucose, FFAs and adipose tissue distribution. However, changes in overall weight (adipose tissue mass) and hepatic fat were the most important determinants of metabolic improvements.
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