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The concept of type 2 diabetes remission is evolving rapidly, and gaining wide public and professional interest, following demonstration that with substantial intentional weight loss almost nine in ten people with type 2 diabetes can reduce their HbA 1c level below the diagnostic criterion (48 mmol/mol [6.5%]) without glucose-lowering medications, and improve all features of the metabolic syndrome. Pursuing nomoglycaemia with older drugs was dangerous because of the risk of side effects and hypoglycaemia, so the conventional treatment target was an HbA 1c concentration of 53 mmol/mol (7%), meaning that diabetes was still present and allowing disease progression. Newer agents may achieve a normal HbA 1c safely and, by analogy with treatments that send cancers or inflammatory diseases into remission, this might also be considered remission. However, although modern glucagon-like peptide-1 receptor agonists and related medications are highly effective for weight loss and glycaemic improvement, and generally safe, many people do not want to take drugs indefinitely, and their cost means that they are not available across much of the world. Therefore, there are strong reasons to explore and research dietary approaches for the treatment of type 2 diabetes. All interventions that achieve sustained weight loss of >10–15 kg improve HbA 1c , potentially resulting in remission if sufficient beta cell capacity can be preserved or restored, which occurs with loss of the ectopic fat in liver and pancreas that is found with type 2 diabetes. Remission is most likely with type 2 diabetes of short duration, lower HbA 1c and a low requirement for glucose-lowering medications. Relapse is likely with weight regain and among those with a poor beta cell reserve. On current evidence, effective weight management should be provided to all people with type 2 diabetes as soon as possible after diagnosis (or even earlier, at the stage of prediabetes, defined in Europe, Australasia, Canada [and most of the world] as ≥42 and <48 mmol/mol [≥6.0 and <6.5%], and in the USA as HbA1c ≥39 and <48 mmol/mol [≥5.7 and <6.5%]). Raising awareness among people with type 2 diabetes and their healthcare providers that remission is possible will enable earlier intervention. Weight loss of >10 kg and remission lasting 1–2 years may also delay vascular complications, although more evidence is needed. The greatest challenge for research is to improve long-term weight loss maintenance, defining cost-effective approaches tailored to the preferences and needs of people living with type 2 diabetes. Graphical Abstract

Weight loss with calorie restriction is the recommended approach for treatment of obesity, but this approach is resource-intensive and difficult to sustain over time. 1 Time-restricted eating is a potentially low-cost and sustainable lifestyle in which daily intake of calories is restricted to a consistent time period of less than 10 hours without explicit attempts to modify diet composition or reduce calories. Chronic disruption of the circadian rhythm increases the risk of obesity and metabolic diseases. Restricting the window of time for eating sustains circadian rhythms and improves metabolism by prolonging the daily fast, which in turn activates cellular pathways that . . .

Abstract Time-restricted feeding (TRF, animal-based studies) and time-restricted eating (TRE, humans) are an emerging behavioral intervention approach based on the understanding of the role of circadian rhythms in physiology and metabolism. In this approach, all calorie intake is restricted within a consistent interval of less than 12 hours without overtly attempting to reduce calories. This article will summarize the origin of TRF/TRE starting with concept of circadian rhythms and the role of chronic circadian rhythm disruption in increasing the risk for chronic metabolic diseases. Circadian rhythms are usually perceived as the sleep-wake cycle and dependent rhythms arising from the central nervous system. However, the recent discovery of circadian rhythms in peripheral organs and the plasticity of these rhythms in response to changes in nutrition availability raised the possibility that adopting a consistent daily short window of feeding can sustain robust circadian rhythm. Preclinical animal studies have demonstrated proof of concept and identified potential mechanisms driving TRF-related benefits. Pilot human intervention studies have reported promising results in reducing the risk for obesity, diabetes, and cardiovascular diseases. Epidemiological studies have indicated that maintaining a consistent long overnight fast, which is similar to TRE, can significantly reduce risks for chronic diseases. Despite these early successes, more clinical and mechanistic studies are needed to implement TRE alone or as adjuvant lifestyle intervention for the prevention and management of chronic metabolic diseases. Graphical Abstract Graphical Abstract

OBJECTIVE:-- Limited data on patients undergoing Roux-en-Y gastric bypass surgery (RY-GBP) suggest that an improvement in insulin secretion after surgery occurs rapidly and thus may not be wholly accounted for by weight loss. We hypothesized that in obese patients with type 2 diabetes the impaired levels and effect of incretins changed as a consequence of RY-GBP. RESEARCH DESIGN AND METHODS-- Incretin (gastric inhibitory peptide [GIP] and glucagon-like peptide-1 [GLP-1]) levels and their effect on insulin secretion were measured before and 1 month after RY-GBP in eight obese women with type 2 diabetes and in seven obese nondiabetic control subjects. The incretin effect was measured as the difference in insulin secretion (area under the curve [AUC]) in response to an oral glucose tolerance test (OGTT) and to an isoglycemic intravenous glucose test. RESULTS:-- Fasting and stimulated levels of GLP-1 and GIP were not different between control subjects and patients with type 2 diabetes before the surgery. One month after RY-GBP, body weight decreased by 9.2 ± 7.0 kg, oral glucose-stimulated GLP-1 (AUC) and GIP peak levels increased significantly by 24.3 ± 7.9 pmol · l⁻¹ · min⁻¹ (P < 0.0001) and 131 ± 85 pg/ml (P = 0.007), respectively. The blunted incretin effect markedly increased from 7.6 ± 28.7 to 42.5 ± 11.3 (P = 0.005) after RY-GBP, at which it time was not different from that for the control subjects (53.6 ± 23.5%, P = 0.284). CONCLUSIONS:-- These data suggest that early after RY-GBP, greater GLP-1 and GIP release could be a potential mediator of improved insulin secretion.

Obesity has emerged as a risk factor for severe coronavirus disease 2019 (COVID-19) infection. To inform treatment considerations the relationship between obesity and COVID-19 complications and the influence of race, ethnicity, and socioeconomic factors deserves continued attention. To determine if obesity is an independent risk factor for severe COVID-19 complications and mortality and examine the relationship between BMI, race, ethnicity, distressed community index and COVID-19 complications and mortality. A retrospective cohort study of 1,019 SARS-CoV-2 positive adult admitted to an academic medical center (n = 928) and its affiliated community hospital (n-91) in New York City from March 1 to April 18, 2020. Median age was 64 years (IQR 52-75), 58.7% were men, 23.0% were Black, and 52.8% were Hispanic. The prevalence of overweight and obesity was 75.2%; median BMI was 28.5 kg/m2 (25.1-33.0). Over the study period 23.7% patients died, 27.3% required invasive mechanical ventilation, 22.7% developed septic shock, and 9.1% required renal replacement therapy (RRT). In the multivariable logistic regression model, BMI was associated with complications including intubation (Odds Ratio [OR]1.03, 95% Confidence Interval [CI]1.01-1.05), septic shock (OR 1.04, CI 1.01-1.06), and RRT (OR1.07, CI 1.04-1.10), and mortality (OR 1.04, CI 1.01-1.06). The odds of death were highest among those with BMI ≥ 40 kg/m2 (OR 2.05, CI 1.04-4.04). Mortality did not differ by race, ethnicity, or socioeconomic distress score, though Black and Asian patients were more likely to require RRT. Severe complications of COVID-19 and death are more likely in patients with obesity, independent of age and comorbidities. While race, ethnicity, and socioeconomic status did not impact COVID-19 related mortality, Black and Asian patients were more likely to require RRT. The presence of obesity, and in some instances race, should inform resource allocation and risk stratification in patients hospitalized with COVID-19.

Infertility, defined as a failure to achieve a pregnancy after at least 12 months of regular and unprotected sexual intercourse, affects 15% of all couples in Canada. Costs associated with assisted reproductive technologies are growing, such that equitable access to high-quality reproductive care is a challenge for health care systems. Obesity is a known modifiable risk factor for female infertility and can affect maternal health; it also puts the offspring's health at risk both as a newborn and later in life (cardiometabolic health). As such, addressing obesity in women seeking to become pregnant would be prudent, especially given that 25% of Canadian women of reproductive age are overweight (body mass index [BMI] 25-30) and 19% are obese (BMI > 30). Here, Belan et al review evidence on the effects of obesity on women's fertility, recommendations regarding obesity management in women with infertility, and evidence of the benefits of weight loss and lifestyle changes for fertility and pregnancy outcomes.

Abstract Context Few studies have examined the clinical characteristics that predict durable, long-term diabetes remission after bariatric surgery. Objective To compare diabetes prevalence and remission rates during 7-year follow-up after Roux-en-Y gastric bypass (RYGB) and laparoscopic gastric banding (LAGB). Design An observational cohort of adults with severe obesity recruited between 2006 and 2009 who completed annual research assessments for up to 7 years after RYGB or LAGB. Setting Ten US hospitals. Participants A total sample of 2256 participants, 827 with known diabetes status at both baseline and at least 1 follow-up visit. Interventions Roux-en-Y gastric bypass or LAGB. Main Outcome Measures Diabetes rates and associations of patient characteristics with remission status. Results Diabetes remission occurred in 57% (46% complete, 11% partial) after RYGB and 22.5% (16.9% complete, 5.6% partial) after LAGB. Following both procedures, remission was greater in younger participants and those with shorter diabetes duration, higher C-peptide levels, higher homeostatic model assessment of β-cell function (HOMA %B), and lower insulin usage at baseline, and with greater postsurgical weight loss. After LAGB, reduced HOMA insulin resistance (IR) was associated with a greater likelihood of diabetes remission, whereas increased HOMA-%B predicted remission after RYGB. Controlling for weight lost, diabetes remission remained nearly 4-fold higher compared with LAGB. Conclusions Durable, long-term diabetes remission following bariatric surgery is more likely when performed soon after diagnosis when diabetes medication burden is low and beta-cell function is preserved. A greater weight-independent likelihood of diabetes remission after RYGB than LAGB suggests mechanisms beyond weight loss contribute to improved beta-cell function after RYGB. Trial Registration clinicaltrials.gov Identifier: NCT00465829.

Background Self-report methods are widely used to assess energy intake but are prone to measurement errors. We aimed to identify under-reported, over-reported, and plausible self-reported energy intake by dietary recalls (rEI) using a standard method (Method 1) that calculates the rEI ratio against measured energy expenditure (mEE) by doubly-labeled water (DLW), and compare it to a novel method (Method 2), which calculates the rEI ratio against measured energy intake (mEI) by the principle of energy balance (EB = mEE + changes in energy stores). Methods The rEI:mEE and rEI:mEI ratios were assessed for each subject. Group cut-offs were calculated for both methods, using the coefficient of variations of rEI, mEE, and mEI. Entries within ± 1SD of the cutoffs were categorized as plausible, < 1SD as under-reported, and > 1SD as over-reported. Kappa statistics was calculated to assess the agreement between both methods. Percentage bias (bβ) was estimated by linear regression. Remaining bias (dβ) was calculated after applying each method cutoffs. Results The percentage of under-reporting was 50% using both methods. Using Method 1, 40.3% of recalls were categorized as plausible, and 10.2% as over-reported. With Method 2, 26.3% and 23.7% recalls were plausible and over-reported, respectively. There was a significant positive relationship between mEI with weight (ß = 21.7, p  < 0.01) and BMI (ß = 48.8, p  = 0.04), but not between rEI with weight (ß = 13.1, p  = 0.06) and BMI (ß = 41.8, p  = 0.11). The rEI relationships were significant when only plausible entries were included using Method 1 (weight: ß = 17.4, p  < 0.01, remaining bias = 49.5%; BMI: ß = 44.6, p  = 0.01, remaining bias = 60.2%) and Method 2 (weight: ß = 19.5, p  < 0.01, remaining bias = 24.9%; BMI: ß = 44.8, p  = 0.03, remaining bias = 56.9%). Conclusions The choice of method significantly impacts plausible and over-reported classification, with the novel method identifying more over-reported entries. While rEI showed no relationships with anthropometric measurements, applying both methods reduced bias. The novel method showed greater bias reduction, suggesting that it may have superior performance when identifying plausible rEI. Clinical trials registration NCT04465721. Graphical Abstract