Body mass index of 30 kg/m2 or higher is used to identify individuals with obesity. In the last 3 decades, the worldwide prevalence of obesity has increased 27.5% for adults and 47.1% for children. ...Obesity is the result of complex relationships between genetic, socioeconomic, and cultural influences. Consumption patterns, urban development, and lifestyle habits influence the prevalence of obesity. The condition may be the result of disease or pharmacologic treatment. It may also be a risk factor for the development of comorbid conditions. Persons who are obese have less school attendance, reduced earning potential, and higher healthcare costs that may result in an economic burden on society. A review of the prevalence and economic consequences of obesity is provided. Potential causes and comorbidities associated with obesity are also discussed.
The prevalence of severe obesity in the United States has increased dramatically, not only among adults but also among children. The increase in childhood severe obesity, defined as 120% of the ...age-specific 95th percentile of body-mass index (BMI), has been alarming; the prevalence has risen from 4% during 1999–2004 to 6% during 2011–2012.
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Although the use of healthy lifestyle approaches to treat younger children with obesity can successfully reduce BMI, the implementation of these approaches among adolescents and adults is much less effective.
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Unfortunately, approximately 90% of children with severe obesity will become obese adults with a BMI (the . . .
Objective:
To formulate clinical practice guidelines for the pharmacological management of obesity.
Participants:
An Endocrine Society-appointed Task Force of experts, a methodologist, and a medical ...writer. This guideline was co-sponsored by the European Society of Endocrinology and The Obesity Society.
Evidence:
This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe the strength of recommendations and the quality of evidence.
Consensus Process:
One group meeting, several conference calls, and e-mail communications enabled consensus. Committees and members of the Endocrine Society, the European Society of Endocrinology, and The Obesity Society reviewed and commented on preliminary drafts of these guidelines. Two systematic reviews were conducted to summarize some of the supporting evidence.
Conclusions:
Weight loss is a pathway to health improvement for patients with obesity-associated risk factors and comorbidities. Medications approved for chronic weight management can be useful adjuncts to lifestyle change for patients who have been unsuccessful with diet and exercise alone. Many medications commonly prescribed for diabetes, depression, and other chronic diseases have weight effects, either to promote weight gain or produce weight loss. Knowledgeable prescribing of medications, choosing whenever possible those with favorable weight profiles, can aid in the prevention and management of obesity and thus improve health.
Obesity is one of the main risk factors for type 2 diabetes (T2D), representing a major worldwide health crisis. Modest weight-loss (≥ 5% but < 10%) can minimize and reduce diabetes-associated ...complications, and significant weight-loss can potentially resolve disease. Treatment guidelines recommend that intensive lifestyle interventions, pharmacologic therapy, and/or metabolic surgery be considered as options for patients with T2D and obesity. The benefits and risks of such interventions should be evaluated in the context of their weight-loss potential, ability to sustain weight change, side effect profile, and costs. Antihyperglycemia therapies have considerable effects on patient weight, prompting careful consideration of weight-loss or weight-neutral therapies for patients with T2D who also have obesity. Metformin, sodium glucose co-transporter 2 inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1 RAs), α-glucosidase inhibitors, and amylin mimetics promote weight-loss. Dipeptidyl peptidase-4 inhibitors and fixed-ratio insulin/GLP-1 RA combination therapies (IDegLira, iGlarLixi) appear to be weight-neutral. Thiazolidinediones, insulin secretagogues (sulfonylureas, meglitinides), and insulins are associated with weight gain. Sulfonylureas are additionally associated with a higher risk of serious hypoglycemia from hyperinsulinemia, making them less suitable for the treatment of patients who are overweight or have obesity. Patients are often overtitrated on basal insulin, resulting in an increased risk of hypoglycemia and weight gain without achieving glycemic goals. Given these observations, the effects of antihyperglycemia agents on weight should be considered when individualizing T2D therapy.
Funding
: Sanofi US, Inc.
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.
Age is a non-modifiable risk factor for the inflammation that underlies age-associated diseases; thus, anti-inflammaging drugs hold promise for increasing health span. Cytokine profiling and ...bioinformatic analyses showed that Th17 cytokine production differentiates CD4+ T cells from lean, normoglycemic older and younger subjects, and mimics a diabetes-associated Th17 profile. T cells from older compared to younger subjects also had defects in autophagy and mitochondrial bioenergetics that associate with redox imbalance. Metformin ameliorated the Th17 inflammaging profile by increasing autophagy and improving mitochondrial bioenergetics. By contrast, autophagy-targeting siRNA disrupted redox balance in T cells from young subjects and activated the Th17 profile by activating the Th17 master regulator, STAT3, which in turn bound IL-17A and F promoters. Mitophagy-targeting siRNA failed to activate the Th17 profile. We conclude that metformin improves autophagy and mitochondrial function largely in parallel to ameliorate a newly defined inflammaging profile that echoes inflammation in diabetes.
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•CD4+ T cells from healthy older people preferentially produce a Th17 profile•Autophagy, but not mitophagy, knockdown activates a Th17 profile in “young” cells•Mitochondrial ROS is needed, but not sufficient, for a Th17 profile in “young” cells•Metformin improves autophagy and mitochondria in parallel to decrease inflammaging
We uncovered a dominant Th17 inflammaging profile made by CD4+ T cells. Knockdown of autophagy in T cells from young subjects activates this profile. In vitro metformin improves autophagy and mitochondrial function in parallel to ameliorate Th17 inflammaging. Oral metformin intervention improves T cell autophagy in people, indicating potential use for age-associated inflammation.
Updates on obesity pharmacotherapy Velazquez, Amanda; Apovian, Caroline M.
Annals of the New York Academy of Sciences,
January 2018, 2018-01-00, 20180101, Letnik:
1411, Številka:
1
Journal Article
Recenzirano
Obesity is a chronic, relapsing disease that necessitates a multidisciplinary approach to management. Behavioral changes are the foundation to management, but adjunctive therapy is often warranted, ...including pharmacologic therapies and/or bariatric surgery. Until recently, treatment options included only short‐term therapy (≤12 weeks), and paths beyond that schedule were challenging, as knowledge of the biology of obesity was lacking. With increased recognition of obesity as a chronic, complex medical disease, newer agents have been approved as long‐term therapy, and the cornerstone of treatment is chronic behavior and lifestyle change. In the last decade, the Food and Drug Administration (FDA) has approved several new weight loss medications for the chronic management of obesity. In this review paper, we provide the latest updates on obesity pharmacotherapy. The main areas we will cover include (1) pharmacological management of obesity, (2) a review of FDA‐approved weight loss medications, (3) comanagement of obesity and its metabolic sequelae (type 2 diabetes mellitus, hypertension, and dyslipidemia), and (4) obesity‐centric prescribing for mental illness, neurological disorders, and contraceptive planning.
Weight loss is crucial for disease prevention among individuals with overweight or obesity. This study aimed to examine associations of weight loss strategies (WLSs) with weight change and type 2 ...diabetes (T2D) risk among US health professionals.
This study included 93,110 participants (24 to 60 years old; 11.6% male) from the Nurses' Health Study (NHS), NHSII, and Health Professionals Follow-Up Study (HPFS) cohorts who were free of T2D, cardiovascular disease, and cancer at baseline (1988 for NHS/HPFS and 1989 for NHSII) for analyses of weight change and 104,180 (24 to 78 years old; 14.2% male) for T2D risk assessment. WLSs used to achieve an intentional weight loss of 4.5+ kg were collected in 1992 (NHS/HPFS)/1993 (NHSII) and grouped into 7 mutually exclusive categories, including low-calorie diet, exercise, low-calorie diet and exercise, fasting, commercial weight loss program (CWLP), diet pills, and FCP (selected at least 2 methods from fasting, CWLP, and pill). The reference group was participants who did not attempt to lose weight. Generalized estimating equations and Cox regression were applied to estimate up to 10-year weight change trajectory and incident T2D risk through 2016 (NHS/HPFS)/2017 (NHSII), respectively. The associations of WLSs with weight change and T2D risk were differential by baseline body weight (Pinteraction < 0.01). Among individuals with obesity, all WLSs tended to associate with less weight gain ranging from -4.2% (95% confidence interval (CI), -5.1% to -3.2%; P < 0.001) for exercise to -0.3% (-1.2% to 0.7%; P > 0.99) for FCP and a lower T2D risk hazard ratios (HRs) ranging from 0.79 (0.66 to 0.95; P = 0.04) for exercise to 0.87 (0.66 to 1.13; P = 0.30) for pill. Such a pattern was less clear among overweight individuals: the difference of weight change varied from -2.5% (-3.0% to -2.1%; P < 0.001) for exercise to 2.0% (1.3% to 2.7%; P < 0.001) for FCP, and HRs of T2D varied from 0.91 (0.77 to 1.07; P = 0.29) for exercise to 1.42 (1.11 to 1.81; P = 0.02) for pill. The pattern was further inverted among lean individuals in that weight change ranged from -0.4% (-0.6% to -0.1%; P = 0.02) for exercise to 3.7% (3.1% to 4.3%; P < 0.001) for FCP, and the HRs of T2D ranged from 1.09 (0.91 to 1.30; P = 0.33) for exercise to 1.54 (1.13 to 2.10; P = 0.008) for pill. Approximately 15.6% to 46.8% of the association between WLSs and the T2D risk was attributed to weight changes. This study was limited by a single assessment of WLSs, heterogeneity within each WLS, and potential misclassification of the timing of weight loss and weight regain.
The current study showed that individuals with obesity who attempted to lose weight, regardless of the WLSs used, tended to gain less body weight and have a lower diabetes risk. In contrast, lean individuals who intentionally lost weight tended to gain more weight and have a higher diabetes risk. These data support the notion that intentional weight loss may not be beneficial for lean individuals and the use of WLSs for achieving weight loss shall be guided by medical indications only.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract Interactions between macrophages and adipocytes influence both metabolism and inflammation. Obesity-induced changes to macrophages and adipocytes lead to chronic inflammation and insulin ...resistance. This paper reviews the various functions of macrophages in lean and obese adipose tissue and how obesity alters adipose tissue macrophage phenotypes. Metabolic disease and insulin resistance shift the balance between numerous pro- and anti-inflammatory regulators of macrophages and create a feed-forward loop of increasing inflammatory macrophage activation and worsening adipocyte dysfunction. This ultimately leads to adipose tissue fibrosis and diabetes. The molecular mechanisms underlying these processes have therapeutic implications for obesity, metabolic syndrome, and diabetes.
Numerous studies show that mitochondrial energy generation determines the effectiveness of immune responses. Furthermore, changes in mitochondrial function may regulate lymphocyte function in ...inflammatory diseases like type 2 diabetes. Analysis of lymphocyte mitochondrial function has been facilitated by introduction of 96-well format extracellular flux (XF96) analyzers, but the technology remains imperfect for analysis of human lymphocytes. Limitations in XF technology include the lack of practical protocols for analysis of archived human cells, and inadequate data analysis tools that require manual quality checks. Current analysis tools for XF outcomes are also unable to automatically assess data quality and delete untenable data from the relatively high number of biological replicates needed to power complex human cell studies. The objectives of work presented herein are to test the impact of common cellular manipulations on XF outcomes, and to develop and validate a new automated tool that objectively analyzes a virtually unlimited number of samples to quantitate mitochondrial function in immune cells. We present significant improvements on previous XF analyses of primary human cells that will be absolutely essential to test the prediction that changes in immune cell mitochondrial function and fuel sources support immune dysfunction in chronic inflammatory diseases like type 2 diabetes.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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