Diabetes, Obesity and Metabolism Now最新文献

Calorie restriction and exercise are mainstay strategies to lose weight. A study published in the Journal of Endocrinology have shown that limiting access to food increases levels of the “hunger hormone”, ghrelin, which may also increase motivation to exercise. The study conducted in mice showed that a surge in levels of appetite-promoting hormone, ghrelin, triggered by a period of fasting prompted mice to initiate voluntary exercise through actions on the brain reward circuitry that increase motivation to eat. It has also been reported to be essential for endurance exercise by increasing metabolism to meet the energy demands of prolonged exercise. These novel findings indicate that strategies to reduce calorie consumption by not snacking or by intermittent fasting, could facilitate overweight people increase and maintain their exercise routine to help lose weight. While previous studies have reported a relationship between ghrelin and exercise, it is not known whether ghrelin levels have a direct effect on motivation to exercise. In this study conducted by investigators from Kurume University School of Medicine in Japan, the relationship between exercise and ghrelin levels in mice, food intake and wheel-running activity were compared in mice given free access to food and those fed only twice a day for a limited time. Although both groups ate a similar amount of food, the restricted mice ran significantly more. Furthermore, genetically modified mice devoid of ghrelin and on the restricted feeding diet ran less than the mice given free access, which was reversed by administering ghrelin. Additionally, mice given free access to food and given ghrelin also ran significantly more. These findings suggest that ghrelin may play an important role in the motivation for both feeding and exercise. If this is replicated in humans, it may provide not only a physiological rationale to encourage and maintain calorie restriction in tandem with exercise, but may also indicate a new therapeutic application for “ghrelin-mimetic” to enhance exercise.

Although increase evidence have reported a link between poor sleep pattern with increased risk of obesity, type 2 diabetes and heart disease, previous studies have mainly focused on specific foods or macronutrients and only assessed duration rather sleep quality. This new study conducted by researchers at Columbia University Irving Medical Center was therefore designed to get a better understanding between overall diet quality and multiple aspects of sleep quality as risk factors for adverse cardiometabolic risks. In this study, researchers analysed the sleep and eating habits of 495 women, ages 20 to 76 from different ethnic groups. The study looked at sleep quality, the time it took to fall asleep, and insomnia. The women also reported on the types and amounts of foods they typically eat throughout the years. The study found that those with worse overall sleep quality consumed more of the added sugars.

A recent study published in Nature investigated total serum IGF1, IGF2, and IGFBP1–7 levels were measured in an age-matched, cross-sectional cohort at varying stages of progression to type 1 diabetes showed that the levels and biovailability of Insulin-like growth factors (IGFs), are reduced during type 1 diabetes development. In the study. Further, IGF1 levels decreased over time in subjects with multiple auto Antibodies and those who progressed to type 1 diabetes, particularly post-diagnosis. This study therefore showed IGFs are dysregulated both before and after the clinical diagnosis of type 1 diabetes and may be used as novel biomarkers predict type 1 diabetes in the future.

URL: https://www.nature.com/articles/s41574-020-0317-0

The twin cycle hypothesis proposed that type 2 diabetes occurs due to accumulation of fat in the liver, which induces insulin resistance, and hyperinsulinaemia – leading to a self-reinforcing cycle, by which insulin stimulates fat production, which spills into the pancreas and causes type 2 diabetes. Based on this, recent experimental and clinical studies have shown that Very low Calorie diet can induce remission of type 2 diabetes. However data from DIRECT suggest that a proportion of patients experienced relapse. A further study published in Cell Metabolism have investigated the mechanism of ‘relapse’ by quantifying liver and pancreas fat at 12 and 24 months. The study showed that those who relapse appears to re-accumulate liver and intra-pancreatic fat, which supports the twin cycle hypothesis. This study was the first to report the underlying physiological changes during a full cycle of disease reversal and re-emergence, and could form a basis for future study to induce long-term diabetes remission following dietary intervention.

URL: https://www.medicalnewstoday.com/articles/327390.php#1

Reduced hepatic insulin clearance (HIC) is a well-recognized consequence of obesity and hepatic fat accumulation in patients with type 2 diabetes. As part of a placebo-controlled 6-month trial of the SGLT2-inhibitor, tofogliflozin, Drs Matsubayashi & colleagues from Japan undertook meal tolerance tests to derive measurements of HIC. They showed significant increases in HIC among SGLT2-inhibitor treated patients, and the increases in HIC correlated with reductions in circulating triglyceride levels and increases in beta-hydroxybutyrate concentrations. Although the underlying mechanisms are not clear, this study provides evidence that SGLT2 inhibitor treatment increases HIC in patients with type 2 diabetes.

This is a nice review article & update by Professors David Owens & Geremia Bolli covering the latest developments with novel, faster acting prandial insulins. Although the development of insulin lispro, aspart and glulisine offered an earlier onset of action and better postprandial glucose control, these insulin analogues still do not fully match the physiological profile of endogenous insulin in the systemic circulation following a meal. Thus, second-generation, even faster acting insulins have emerged in the form of faster-acting aspart, ultra-rapid lispro and BioChaperone lispro. A number of clinical trials with these agents have already been published in DOM. Owens & Bolli review the phase 3 trials in type 1 and type 2 diabetes, in particular with faster-acting aspart and ultra-rapid lispro, to show further incremental improvements in postprandial glycemic control.

Cardiovascular outcome trials have been completed with semaglutide using the s.c (SUSTAIN 6) and oral (PIONEER) formulations. This post-hoc analysis combined the data from both trials to investigate the occurrence of MACE (major adverse cardiovascular events) events and hospitalization for heart failure according to baseline CV risk, i.e the presence or absence of prior CV disease and/or CKD; prior MI or stroke; or prior evidence of heart failure. Husain et al showed that the hazard ratios for MACE were <1.0 in all subgroups, except those with prior heart failure. Thus, the cardiovascular risk lowering benefits of semaglutide seem to apply to a broad patient population with varying levels of baseline CV risk.

DISCOVER is a multinational 3-yr prospective observational study of second-line glucose lowering therapies. In this study, the DISCOVER authors have developed and validated two prognostic models to evaluate the durability of glycemic control after initiating second-line therapy in patients failing on metformin. Durable control was defined as consecutive HbA1c levels ‘on target’ at 6, 12 and 24 months following second-line therapy initiation. These predictive models, which will be available to clinicians & use various clinical inputs, provide an estimation of the probability of achieving & maintaining glycemic control over 2-years following initiation of different second-line agents as add-on to metformin.

A research group from Cardiff, UK, has analysed data from the DEPICT clinical trial program and used a novel modelling approach to investigate the inter-relationships between hypoglycaemia, BMI and quality of life (QoL). Episodes of severe hypoglycaemia were associated with a significant increase in the ‘hypoglycemia fear score’ (HFS), and there was evidence that increased HFS and/or increased BMI resulted in significantly lower patient-reported QoL. Among type 1 diabetes patients treated with the SGLT2 inhibitor dapagliflozin there were significant (>3-point) improvements in overall patient treatment satisfaction (measured using the Diabetes Treatment Satisfaction Questionnaire).

There is considerable interest and anticipation in the metabolic profile of novel dual agonists currently in clinical development, especially Lilly's tirzepatide which is administered once weekly by subcutaneous injection. Dual agonists may be clinically useful both as anti-obesity and glucose-lowering agents. This phase II study of tirzepatide was conducted over 12-weeks in >100 patients with type 2 diabetes to evaluate different dose-escalation regimens using a placebo-controlled randomised design. The primary endpoint of the trial was HbA1c lowering after once-weekly tirzepatide vs placebo. Baseline HbA1c and BMI were 8.4% and 31.9, respectively. The authors report clinically significant HbA1c reductions with tirzepatide, and found that a lower starting dose, combined with smaller dose increments, resulted in better tolerability.

As the Complementary Medicines industry grows in popularity, there is an assortment of herbal medicines available which purport to facilitate weight loss among people who are overweight but the strength of the underlying evidence is variable. Few, if any, herbal medicines, have been evaluated as anti-obesity agents in randomised controlled trials (RCTs), and such trials are often under-powered, of short duration and limited in their design. Now, a research group from Sydney (Maunder et al) has undertaken a systematic review and meta-analysis of the literature, which included 54 placebo-controlled trials of various herbal medicines. On the basis that 2.5 kg of weight loss is a clinically-significant effect, the authors found that herbal products were generally safe and well tolerated but concluded that there is insufficient evidence to recommend any of the herbal medicines for weight loss.