The Lancet Diabetes & Endocrinology最新文献

Over the last decade, goal-directed management of osteoporosis has been developed as a concept. In 2024, a working group of the American Society for Bone and Mineral Research (ASBMR) determined that this concept should include specific bone mineral density (BMD) targets during treatment, to ensure optimal fracture risk reduction. Two observations were key to this recommendation: that higher on-treatment BMDs are associated with lower fracture risks in several studies, and that, in a meta-regression of individual clinical trials, agents producing larger increases in BMD also produced greater reduction in fracture risk. However, the inferences drawn from these studies might be unsound. First, on-treatment BMD is the sum of baseline BMD and its change on therapy. In trials in which these variables have both been considered, it was found that the influence of on-treatment BMD is substantially a reflection of the effect of baseline BMD on fracture risk rather than an effect of on-treatment BMD change. Second, the meta-regression findings are heavily dependent on the inclusion of less effective treatments in the analysis. Among more effective antiresorptives, no such relationship is seen. For example, although denosumab has greater effects on BMD than zoledronate, these agents have similar anti-fracture efficacy in trials. Therefore, a key conclusion of the treat-to-BMD-target framework-that denosumab is needed for many patients to reach their BMD targets-has no clinical trial support, suggesting the framework is flawed. Thus, use of BMD treatment targets in osteoporosis management is not supported by available evidence, so the frequent BMD measurements required by the treat-to-target framework will increase costs without demonstrable benefit.

Incretin-based therapies, including GLP-1 receptor agonists and dual GLP-1-GIP receptor agonists, have transformed obesity management, producing substantial weight loss and cardiometabolic benefits, with potential improvements in obesity-related complications, physical function, quality of life, and psychological wellbeing for many individuals. However, reduced appetite, rapid weight loss, gastrointestinal adverse effects, and changes in eating behaviour might create nutritional, functional, or psychological risks in some individuals. This EASO-EFAD-ECPO Consensus Statement outlines pragmatic nutritional, functional, and psychological considerations during incretin-based therapy treatment. We synthesise evidence on medical nutrition therapy, including protein targets during weight loss, dietary quality, and mitigation of gastrointestinal adverse events. We discuss pragmatic approaches that could help support preservation of fat-free mass and physical function during weight loss, including adequate protein intake and progressive resistance exercise. We emphasise the psychological and identity-related challenges during incretin-based therapy, including shifts in food reward, coping, and social connection, and recommend psychological screening, with integrated support where needed. We propose pragmatic monitoring during weight loss, including diet quality, micronutrient risk, and functional measures, with body-composition assessment where indicated. We suggest approaches to address disparities in access and adherence to ensure equity. We discuss the importance of shared decision making with the patient in decisions to start, up-titrate, delay, pause, down-titrate, or discontinue incretin-based therapies, considering the physical and psychological risks of treating versus not treating. Finally, we identify future research priorities, including longitudinal research on micronutrient status, macronutrient requirements, changes in dietary patterns and food choices, musculoskeletal outcomes, unique dosing schedules, and post-cessation maintenance to optimise safety, efficacy, and the patient experience.

Background: SGLT2 inhibitors increase the risk of ketoacidosis, but data from routine clinical practice are scarce. We used nationwide registers with the aim of assessing the incidence, risk factors, and prognosis of ketoacidosis during SGLT2 inhibitor treatment in patients with type 2 diabetes.

Methods: In this cohort and nested case-control study we used data from three Scandinavian countries. In a cohort of SGLT2 inhibitor-treatment episodes among patients with type 2 diabetes aged at least 18 years in Sweden, Denmark, and Norway, we estimated ketoacidosis incidence. Using a nested case-control design (matched on age, sex, region of birth, calendar time, and time since treatment initiation), we assessed risk factors and precipitating or co-occurring events. Changes in diabetes medications were evaluated.

Findings: The study period was Jan 1, 2013, to Dec 31, 2021, in Denmark and Sweden, and Jan 1, 2013, to Dec 31, 2022, in Norway. We included 322 597 treatment episodes among 282 282 patients with type 2 diabetes (mean age 63 years, 116 521 [36·1%] of 322 597 women). During a median (IQR) follow-up of 1·3 (0·7-2·8) years, 1452 ketoacidosis events occurred (incidence 2·43 per 1000 person-years). Although highest shortly after initiation, risk persisted throughout follow-up. Strong risk factors included high HbA_1c (≥83 vs ≤52 mmol/mol: odds ratio [OR] 15·37 [95% CI 11·50-20·53]), malnutrition (OR 10·54 [7·32-15·18]), previous ketoacidosis (OR 10·40 [7·09-15·24]), low BMI (<20 kg/m²vs 20 to <25 kg/m²: OR 9·98 [5·68-17·53]), and recent hypoglycaemia (OR 5·22 [2·60-10·49]). Infection was the most common precipitating or co-occurring event (454 [31·8%] of 1428 vs 862 [6·1%] of 14 233 for ketoacidosis cases vs controls; OR 7·60 [6·62-8·71]). The strongest associations were observed for alcohol intoxication, acute renal events, acute abdomen, stroke, and major surgery, although associations for some transient exposures, particularly milder conditions, might have been overestimated because of under-registration among controls. Exploratory analyses suggested that the observed associations were largely general to patients with type 2 diabetes rather than specific to SGLT2 inhibitor use. At 1 year after ketoacidosis, 211 (25·1%) of 842 remained on SGLT2 inhibitors and insulin use increased from 269 (31·9%) of 842 to 615 (73·0%) of 842.

Interpretation: Ketoacidosis risk with SGLT2 inhibitors varies greatly by patient characteristics and is not confined to early in treatment. Risk should be assessed throughout treatment, and patients should be instructed to pause treatment during acute illness and stress.

Funding: Region Stockholm, Swedish Society of Medicine, Karolinska Institutet.

Intermittent fasting is now the third most commonly practiced diet in the USA. Yet, despite more than 225 clinical trials-including nearly 40 in patients with diabetes or prediabetes-intermittent fasting has not yet been recommended as part of the American Diabetes Association (ADA) Standards of Care or the International Diabetes Federation (IDF) Global Clinical Practice Recommendations. In this Personal View, we start by synthesising evidence from trials in patients with type 2 diabetes, type 1 diabetes, prediabetes, and gestational diabetes. In adults with type 2 diabetes, diverse types of intermittent fasting, such as time-restricted eating, the 5:2 diet, and the fasting mimicking diet, reduce HbA_1c (typically by 0·3-1·2%), fasting glucose, 24-h glucose, and bodyweight relative to usual eating patterns. Moreover, intermittent fasting is as effective as calorie restriction for improving glycaemic control and does not increase the risk of hypoglycaemia when medications are adjusted using simple rules. Intermittent fasting might also reduce glycaemia in adults with prediabetes, whereas there are insufficient data to recommend its use in people with type 1 or gestational diabetes. Therefore, we argue that the evidence base has sufficiently matured to warrant including intermittent fasting in clinical practice guidelines as one of several evidence-based lifestyle options for type 2 diabetes. We also provide practical guidance for clinicians on prescribing intermittent fasting and safely managing people with diabetes.