Aim
To quantify the effect of weight loss on glycated haemoglobin (HbA1c) at group level, based on data from published weight loss trials in overweight and obese patients with type 2 diabetes (T2D).
...Methods
A systematic literature search in MEDLINE, EMBASE and Cochrane CENTRAL (January 1990 through December 2012) was conducted to identify prospective trials of energy‐reduced diets, obesity drugs or bariatric surgery in adult, overweight and obese patients with T2D. Based on clinical data with follow‐up from 3 to 24 months, a linear model was developed to describe the effect of weight reduction on HbA1c.
Results
The literature search identified 58 eligible articles consisting of 124 treatment groups and 17 204 subjects, yielding a total of 250 data points with concurrent mean changes from baseline in weight and HbA1c. The model‐based analyses indicated a linear relationship between weight loss and HbA1c reduction, with an estimated mean HbA1c reduction of 0.1 percentage points for each 1 kg of reduced body weight for the overall population. Baseline HbA1c was a significant covariate for the relationship between weight loss and HbA1c: high HbA1c at baseline was associated with a greater reduction in HbA1c for the same degree of weight loss. The collected trial data also indicated weight‐loss‐dependent reductions in antidiabetic medication.
Conclusions
At group level, weight loss in obese and overweight patients with T2D was consistently accompanied by HbA1c reduction in a dose‐dependent manner. The model developed in the present study estimates that for each kg of mean weight loss, there is a mean HbA1c reduction of 0.1 percentage points. HbA1c‐lowering is greater in populations with poor glycaemic control than in well controlled populations with the same degree of weight loss. This summary of data from previous trials regarding the effect of weight reduction on HbA1c may be used to support the design and interpretation of future studies that aim to demonstrate the efficacy of weight loss interventions for T2D treatment.
The double burden of malnutrition (DBM), defined as the simultaneous manifestation of both undernutrition and overweight and obesity, affects most low-income and middle-income countries (LMICs). This ...Series paper describes the dynamics of the DBM in LMICs and how it differs by socioeconomic level. This Series paper shows that the DBM has increased in the poorest LMICs, mainly due to overweight and obesity increases. Indonesia is the largest country with a severe DBM, but many other Asian and sub-Saharan African countries also face this problem. We also discuss that overweight increases are mainly due to very rapid changes in the food system, particularly the availability of cheap ultra-processed food and beverages in LMICs, and major reductions in physical activity at work, transportation, home, and even leisure due to introductions of activity-saving technologies. Understanding that the lowest income LMICs face severe levels of the DBM and that the major direct cause is rapid increases in overweight allows identifying selected crucial drivers and possible options for addressing the DBM at all levels.
Weight loss from calorie restriction (CR) and/or endurance exercise training (EX) is cardioprotective. However CR and EX also have weight loss-independent benefits.
We tested the hypothesis that ...weight loss from calorie restriction and exercise combined (CREX) improves cardiovascular disease (CVD) risk factors more so than similar weight loss from CR or EX alone.
Overweight, sedentary men and women (n = 52; aged 45-65 y) were randomly assigned to undergo 6-8% weight loss by using CR, EX, or CREX. Outcomes were measured before and after weight loss and included maximal oxygen consumption (VO2max), resting blood pressure, fasting plasma lipids, glucose, C-reactive protein, and arterial stiffness carotid-femoral pulse wave velocity (PWV) and carotid augmentation index (AI). Values are means ± SEs.
Reductions in body weight (∼7%) were similar in all groups. VO2max changed in proportion to the amount of exercise performed (CR, -1% ± 3%; EX, +22% ± 3%; and CREX, +11% ± 3%). None of the changes in CVD risk factors differed between groups. For all groups combined, decreases were observed for systolic and diastolic blood pressure (-5 ± 1 and -4 ± 1 mm Hg, respectively; both P < 0.0008), total cholesterol (-17 ± 4 mg/dL; P < 0.0001), non-HDL cholesterol (-16 ± 3 mg/dL; P < 0.0001), triglycerides (-18 ± 8 mg/dL; P = 0.03), and glucose (-3 ± 1 mg/dL; P = 0.0003). No changes were observed for HDL cholesterol (P = 0.30), C-reactive protein (P = 0.10), PWV (P = 0.30), or AI (P = 0.84). These changes would be expected to decrease the lifetime risk of CVD from 46% to 36%.
Matched weight losses from CR, EX, and CREX have substantial beneficial effects on CVD risk factors. However, the effects are not additive when weight loss is matched. This trial was registered at clinicaltrials.gov as NCT00777621.
Objective To estimate the risks of major congenital malformations in the offspring of mothers who are underweight (body mass index (BMI) <18.5), overweight (BMI 25 to <30), or in obesity classes I ...(BMI 30 to <35), II (35 to <40), or III (≥40) compared with offspring of normal weight mothers (BMI 18.5 to <25) in early pregnancy.Design Population based cohort study.Setting Nationwide Swedish registries.Participants 1 243 957 liveborn singleton infants from 2001 to 2014 in Sweden. Data on maternal and pregnancy characteristics were obtained by individual record linkages.Exposure Maternal BMI at the first prenatal visit.Main outcome measures Offspring with any major congenital malformation, and subgroups of organ specific malformations diagnosed during the first year of life. Risk ratios were estimated using generalised linear models adjusted for maternal factors, sex of offspring, and birth year.Results A total of 43 550 (3.5%) offspring had any major congenital malformation, and the most common subgroup was for congenital heart defects (n=20 074; 1.6%). Compared with offspring of normal weight mothers (risk of malformations 3.4%), the proportions and adjusted risk ratios of any major congenital malformation among the offspring of mothers with higher BMI were: overweight, 3.5% and 1.05 (95% confidence interval 1.02 to 1.07); obesity class I, 3.8% and 1.12 (1.08 to 1.15), obesity class II, 4.2% and 1.23 (1.17 to 1.30), and obesity class III, 4.7% and 1.37 (1.26 to 1.49). The risks of congenital heart defects, malformations of the nervous system, and limb defects also progressively increased with BMI from overweight to obesity class III. The largest organ specific relative risks related to maternal overweight and increasing obesity were observed for malformations of the nervous system. Malformations of the genital and digestive systems were also increased in offspring of obese mothers.Conclusions Risks of any major congenital malformation and several subgroups of organ specific malformations progressively increased with maternal overweight and increasing severity of obesity. For women who are planning pregnancy, efforts should be encouraged to reduce adiposity in those with a BMI above the normal range.
Overweight and obesity are epidemic among persons with serious mental illness, yet weight-loss trials systematically exclude this vulnerable population. Lifestyle interventions require adaptation in ...this group because psychiatric symptoms and cognitive impairment are highly prevalent. Our objective was to determine the effectiveness of an 18-month tailored behavioral weight-loss intervention in adults with serious mental illness.
We recruited overweight or obese adults from 10 community psychiatric rehabilitation outpatient programs and randomly assigned them to an intervention or a control group. Participants in the intervention group received tailored group and individual weight-management sessions and group exercise sessions. Weight change was assessed at 6, 12, and 18 months.
Of 291 participants who underwent randomization, 58.1% had schizophrenia or a schizoaffective disorder, 22.0% had bipolar disorder, and 12.0% had major depression. At baseline, the mean body-mass index (the weight in kilograms divided by the square of the height in meters) was 36.3, and the mean weight was 102.7 kg (225.9 lb). Data on weight at 18 months were obtained from 279 participants. Weight loss in the intervention group increased progressively over the 18-month study period and differed significantly from the control group at each follow-up visit. At 18 months, the mean between-group difference in weight (change in intervention group minus change in control group) was -3.2 kg (-7.0 lb, P=0.002); 37.8% of the participants in the intervention group lost 5% or more of their initial weight, as compared with 22.7% of those in the control group (P=0.009). There were no significant between-group differences in adverse events.
A behavioral weight-loss intervention significantly reduced weight over a period of 18 months in overweight and obese adults with serious mental illness. Given the epidemic of obesity and weight-related disease among persons with serious mental illness, our findings support implementation of targeted behavioral weight-loss interventions in this high-risk population. (Funded by the National Institute of Mental Health; ACHIEVE ClinicalTrials.gov number, NCT00902694.).
Adults with type 2 diabetes mellitus often have limitations in mobility that increase with age. An intensive lifestyle intervention that produces weight loss and improves fitness could slow the loss ...of mobility in such patients.
We randomly assigned 5145 overweight or obese adults between the ages of 45 and 74 years with type 2 diabetes to either an intensive lifestyle intervention or a diabetes support-and-education program; 5016 participants contributed data. We used hidden Markov models to characterize disability states and mixed-effects ordinal logistic regression to estimate the probability of functional decline. The primary outcome was self-reported limitation in mobility, with annual assessments for 4 years.
At year 4, among 2514 adults in the lifestyle-intervention group, 517 (20.6%) had severe disability and 969 (38.5%) had good mobility; the numbers among 2502 participants in the support group were 656 (26.2%) and 798 (31.9%), respectively. The lifestyle-intervention group had a relative reduction of 48% in the risk of loss of mobility, as compared with the support group (odds ratio, 0.52; 95% confidence interval, 0.44 to 0.63; P<0.001). Both weight loss and improved fitness (as assessed on treadmill testing) were significant mediators of this effect (P<0.001 for both variables). Adverse events that were related to the lifestyle intervention included a slightly higher frequency of musculoskeletal symptoms at year 1.
Weight loss and improved fitness slowed the decline in mobility in overweight adults with type 2 diabetes. (Funded by the Department of Health and Human Services and others; ClinicalTrials.gov number, NCT00017953.).
Although the rising pandemic of obesity has received major attention in many countries, the effects of this attention on trends and the disease burden of obesity remain uncertain.
We analyzed data ...from 68.5 million persons to assess the trends in the prevalence of overweight and obesity among children and adults between 1980 and 2015. Using the Global Burden of Disease study data and methods, we also quantified the burden of disease related to high body-mass index (BMI), according to age, sex, cause, and BMI in 195 countries between 1990 and 2015.
In 2015, a total of 107.7 million children and 603.7 million adults were obese. Since 1980, the prevalence of obesity has doubled in more than 70 countries and has continuously increased in most other countries. Although the prevalence of obesity among children has been lower than that among adults, the rate of increase in childhood obesity in many countries has been greater than the rate of increase in adult obesity. High BMI accounted for 4.0 million deaths globally, nearly 40% of which occurred in persons who were not obese. More than two thirds of deaths related to high BMI were due to cardiovascular disease. The disease burden related to high BMI has increased since 1990; however, the rate of this increase has been attenuated owing to decreases in underlying rates of death from cardiovascular disease.
The rapid increase in the prevalence and disease burden of elevated BMI highlights the need for continued focus on surveillance of BMI and identification, implementation, and evaluation of evidence-based interventions to address this problem. (Funded by the Bill and Melinda Gates Foundation.).
High dairy/milk intake has been associated with a low risk of type 2 diabetes observationally, but whether this represents a causal association is unknown.
We tested the hypothesis that high milk ...intake is associated with a low risk of type 2 diabetes and of overweight-obesity, observationally and genetically.
In 97,811 individuals from the Danish general population, we examined the risk of incident type 2 diabetes and of overweight-obesity by milk intake observationally and by LCT-13910 C/T genotype polymorphism (rs4988235) upstream from the lactase (LCT) gene, where TT and TC genotypes are associated with lactase persistence and CC with nonpersistence.
Observationally for any compared with no milk intake, the HR for type 2 diabetes was 1.10 (95% CI: 0.98, 1.24; P = 0.11), whereas the OR for overweight-obesity was 1.06 (1.02, 1.09; P = 0.002). Median milk intake was 5 glasses/wk (IQR: 0-10) for lactase TT/TC persistence and 3 (0-7) for CC nonpersistence. Genetically for lactase TT/TC persistence compared with CC nonpersistence, the OR was 0.96 (0.86, 1.08; P = 0.50) for type 2 diabetes and 1.06 (1.00, 1.12; P = 0.04) for overweight-obesity. In a stratified analysis for type 2 diabetes, corresponding values in those with and without milk intake were 0.88 (0.76, 1.03; P = 0.11) and 1.35 (1.07, 1.70; P = 0.01) (P-interaction: 0.002), whereas no gene-milk interaction on overweight-obesity was found. For a 1-glass/wk higher milk intake, the genetic risk ratio for type 2 diabetes was 0.99 (0.93, 1.06), and the corresponding observational risk was 1.01 (1.00, 1.01). For overweight-obesity, the corresponding values were 1.01 (1.00, 1.02) genetically and 1.00 (1.00, 1.01) observationally.
High milk intake is not associated with a low risk of type 2 diabetes or overweight-obesity, observationally or genetically via lactase persistence. The higher risk of type 2 diabetes in lactase-persistent individuals without milk intake likely is explained by collider stratification bias.
Very low calorie ketogenic diet (VLCKD) has been proposed as a promising option to achieve a significant weight loss in a short time period. We conducted a systematic review and meta-analysis to ...evaluate its efficacy and safety in patients with overweight and obesity. Four databases were searched on May 2019. Studies reporting data on body weight, body mass index (BMI), waist circumference, body composition, blood pressure, HbA1c, lipids, and markers of liver and kidney function were selected. Discontinuation was also assessed. Twelve studies were included. VLCKD was associated with weight losses of −10.0 kg (I
2
= 6%) and − 15.6 kg (I
2
= 37%) in studies with a ketogenic phase up to and of at least four weeks, respectively. The weight lost during the ketogenic phase was stable in the subsequent follow-up up to two years (
p
= 0.12). Also, VLCKD was associated with reductions of BMI (−5.3 kg/m
2
), waist circumference (−12.6 cm), HbA1c (−0.7%), total cholesterol (−28 mg/dl), triglycerides (−30 mg/dl), AST (−7 U/l), ALT (−8 U/l), GGT (−8 U/l), systolic and diastolic blood pressure (−8 and − 7 mmHg, respectively). No changes in LDL cholesterol, HDL cholesterol, serum creatinine, serum uric acid and serum potassium were found. Serum sodium increased during VLCKD (+1.6 mEq/l). The overall prevalence of patients discontinuing VLCKD was 7.5% and this was similar to patients undergoing a low calorie diet (
p
= 0.83). The present review supports the use of VLCKD as an effective strategy for the management of overweight and obesity. Future guidelines should include a specific recommendation for this intervention.
Abstract
Background
The enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) determines prereceptor metabolism and activation of glucocorticoids within peripheral tissues. Its dysregulation has ...been implicated in a wide array of metabolic diseases, leading to the development of selective 11β-HSD1 inhibitors. We examined the impact of the reversible competitive 11β-HSD1 inhibitor, AZD4017, on the metabolic profile in an overweight female cohort with idiopathic intracranial hypertension (IIH).
Methods
We conducted a UK multicenter phase II randomized, double-blind, placebo-controlled trial of 12-week treatment with AZD4017. Serum markers of glucose homeostasis, lipid metabolism, renal and hepatic function, inflammation and androgen profiles were determined and examined in relation to changes in fat and lean mass by dual-energy X-ray absorptiometry.
Results
Patients receiving AZD4017 showed significant improvements in lipid profiles (decreased cholesterol, increased high-density lipoprotein HDL and cholesterol/HDL ratio), markers of hepatic function (decreased alkaline phosphatase and gamma-glutamyl transferase), and increased lean muscle mass (1.8%, P < .001). No changes in body mass index, fat mass, and markers of glucose metabolism or inflammation were observed. Patients receiving AZD4017 demonstrated increased levels of circulating androgens, positively correlated with changes in total lean muscle mass.
Conclusions
These beneficial metabolic changes represent a reduction in risk factors associated with raised intracranial pressure and represent further beneficial therapeutic outcomes of 11β-HSD1 inhibition by AZD4017 in this overweight IIH cohort. In particular, beneficial changes in lean muscle mass associated with AZD4017 may reflect new applications for this nature of inhibitor in the management of conditions such as sarcopenia.
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