DSE
Dermatan-sulfate epimerase precursor (EC 5.1.3.19) (DS epimerase) (Chondroitin-glucuronate 5-epimerase) (Squamous cell carcinoma antigen recognized by T-cells 2) (SART-2) [SART2]
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Type 2 diabetes mellitus and obesity are sometimes described as conditions that accelerate aging. Multidomain lifestyle interventions have shown promise to slow the accumulation of age-related diseases, a hallmark of aging. However, they have not been assessed among at-risk individuals with these two conditions. We examined the relative impact of 8 years of a multidomain lifestyle intervention on an index of multimorbidity. Randomized controlled clinical trial comparing an intensive lifestyle intervention (ILI) that targeted weight loss through caloric restriction and increased physical activity with a control condition of diabetes support and education (DSE). Sixteen U.S. academic centers. A total of 5,145 volunteers, aged 45 to 76, with established type 2 diabetes mellitus and overweight or obesity who met eligibility criteria for a randomized controlled clinical trial. A multimorbidity index that included nine age-related chronic diseases and death was tracked over 8 years of intervention delivery. Among individuals assigned to DSE, the multimorbidity index scores increased by an average of .98 (95% confidence interval [CI] = .94-1.02) over 8 years, compared with .89 (95% CI = .85-.93) among those in the multidomain ILI, which was a 9% difference (P = .003). Relative intervention effects were similar among individuals grouped by baseline body mass index, age, and sex, and they were greater for those with lower levels of multimorbidity index scores at baseline. Increases in multimorbidity over time among adults with overweight or obesity and type 2 diabetes mellitus may be slowed by multidomain ILI. J Am Geriatr Soc 68:2249-2256, 2020.
Keywords
- aging
- multidomain intervention
- obesity
- type 2 diabetes mellitus
The impact of weight loss intervention on disability-free life expectancy in adults with diabetes is unknown. We examined the impact of a long-term weight loss intervention on years spent with and without physical disability. Overweight or obese adults with type 2 diabetes age 45-76 years ([i]n[/i] = 5,145) were randomly assigned to a 10-year intensive lifestyle intervention (ILI) or diabetes support and education (DSE). Physical function was assessed annually for 12 years using the 36-Item Short Form Health Survey. Annual incidence of physical disability, mortality, and disability remission were incorporated into a Markov model to quantify years of life spent active and physically disabled. Physical disability incidence was lower in the ILI group (6.0% per year) than in the DSE group (6.8% per year) (incidence rate ratio 0.88 [95% CI 0.81-0.96]), whereas rates of disability remission and mortality did not differ between groups. ILI participants had a significant delay in moderate or severe disability onset and an increase in number of nondisabled years ([i]P[/i] < 0.05) compared with DSE participants. For a 60-year-old, this effect translates to 0.9 more disability-free years (12.0 years [95% CI 11.5-12.4] vs. 11.1 years [95% CI 10.6-11.7]) but no difference in total years of life. In stratified analyses, ILI increased disability-free years of life in women and participants without cardiovascular disease (CVD) but not in men or participants with CVD. Long-term lifestyle interventions among overweight or obese adults with type 2 diabetes may reduce long-term disability, leading to an effect on disability-free life expectancy but not on total life expectancy.
MeSH Terms
- Adult
- Aged
- Aged, 80 and over
- Cardiovascular Diseases
- Diabetes Complications
- Diabetes Mellitus, Type 2
- Disabled Persons
- Female
- Health Education
- Humans
- Incidence
- Life Expectancy
- Life Style
- Male
- Middle Aged
- Obesity
- Overweight
- Risk Reduction Behavior
- Weight Loss
To test the hypothesis that an 8-year intensive lifestyle intervention (ILI) suppresses aging-dependent changes in regional lean mass (LM) and fat mass (FM) among people with overweight/obesity and type 2 diabetes. Regional body composition was measured by dual-energy X-ray absorptiometry within a subset of 1,019 volunteers (45-75 years old) in the Look AHEAD study randomized to ILI or diabetes support and education (DSE). The ILI goal was to achieve and maintain ≥7% weight loss through increased physical activity and reduced caloric intake. Over 8 years, the DSE group exhibited a linear loss of LM and FM. During year 1, the ILI group lost LM and FM. Between years 1 and 8, the ILI group regained most FM in all regions; regional LM converged with that of the DSE group; the percent of LM loss was greater for the leg than for the trunk. Among both groups, regional LM and FM change was proportional to the size of the region, trunk > leg > arm. Aging-dependent LM losses, particularly in the leg region, were not suppressed by ILI. The long-term consequences of rapid LM and FM loss and subsequent regain mostly as fat are unknown.
MeSH Terms
- Absorptiometry, Photon
- Aged
- Aging
- Body Composition
- Diabetes Mellitus, Type 2
- Energy Intake
- Female
- Health Education
- Humans
- Life Style
- Male
- Middle Aged
- Obesity
- Overweight
- Weight Loss
A sigmoid ventricular septum (SVS) may be related to normal aging, but some people with an SVS develop a left ventricular outflow tract (LVOT) obstruction (defined as a gradient of >30 mmHg). Therefore, we investigated the association of LVOT obstructions with an SVS by dobutamine stress echocardiography (DSE) and assessed the possible mechanism of the latent LVOT obstruction. DSE was performed in 64 subjects with SVS (mean age: 73.3±7.7 years; 36 women) without an LVOT obstruction. In 40 of the 64 subjects, an LVOT obstruction occurred during the DSE (defined as latent obstruction). At rest, the subjects with a latent obstruction had a shorter end-systolic mitral leaflet tethering distance ("α" distance, i.e. the distance between the tip of the posterior papillary muscle and the contralateral anterior mitral annulus) than those without one (29.9±4.2 mm versus 35.2±4.6 mm), as well as a smaller end-systolic LVOT diameter (13.4±2.7 mm versus 16.1±3.4 mm) and larger ejection fraction (72.0±5.0% versus 67.8±5.9%) (all p<0.05). They also had a higher LV outflow velocity at rest (1.23±0.24 m/s versus 1.03±0.24 m/s) and during the Valsalva maneuver (1.31±0.27 m/s versus 1.03±0.27 m/s) (both p<0.05). After adjusting for these parameters, the resting end-systolic "α" distance and LV outflow velocity at rest remained independent predictors of a latent obstruction. A short leaflet tethering distance ("α") was the major determinant of a latent obstruction, suggesting that a mitral leaflet displacement/redundancy caused by a short "α" distance contributes to the LVOT obstruction.
MeSH Terms
- Aged
- Aged, 80 and over
- Aging
- Dobutamine
- Echocardiography, Stress
- Female
- Humans
- Male
- Ventricular Outflow Obstruction
- Ventricular Septum
In the cerebellum of juvenile mice or rats, endocannabinoids are shown to mediate depolarization-induced suppression of excitation (DSE) and retrograde suppression induced by activation of type 1 metabotropic glutamate receptor (mGluR1) at parallel fiber (PF) to Purkinje cell (PC) synapses. However, recent studies showed that glutamate also mediated retrograde signaling through presynaptic kainate receptors in the cerebellum of young adult mice and rats. We reexamined this possibility in C57BL/6 mice at postnatal day 20-35 (P20-P35) and in Sprague-Dawley rats at P18-P24. We found that DSE at PF-PC synapses was abolished by AM251, a cannabinoid receptor antagonist, and by tetrahydrolipstatin (THL), a blocker of diacylglycerol lipase (DGL) that produces an endocannabinoid, 2-arachidonoylglycerol (2-AG). AM251 and THL did not affect depolarization-induced Ca(2 ) transients in PCs, and THL did not suppress cannabinoid sensitivity of PFs. Moreover, DSE at PF-PC synapses was absent in CB(1) knockout mice. AM251 also eliminated transient suppression of PF-PC synaptic transmission following a brief burst of PF stimulation, a phenomenon known to be mediated by mGluR1. These results suggest that DSE and mGluR1-mediated suppression in young adult PCs are mediated by endocannabinoids, and that glutamate, if any, has little contribution.
MeSH Terms
- Aging
- Animals
- Calcium
- Cannabinoid Receptor Antagonists
- Cannabinoid Receptor Modulators
- Cerebellum
- Endocannabinoids
- Enzyme Inhibitors
- Glutamic Acid
- Humans
- In Vitro Techniques
- Lactones
- Mice
- Mice, Inbred C57BL
- Mice, Knockout
- Neural Inhibition
- Orlistat
- Piperidines
- Purkinje Cells
- Pyrazoles
- Rats
- Rats, Sprague-Dawley
- Receptor, Cannabinoid, CB1
- Receptors, Cannabinoid
- Synaptic Transmission