The storage of triglyceride (TG) droplets in nonadipose tissues is called ectopic fat storage. Ectopic fat is associated with insulin resistance and type 2 diabetes mellitus (T2DM). Not the triglycerides per se but the accumulation of intermediates of lipid metabolism in organs, such as the liver, skeletal muscle, and heart seem to disrupt metabolic processes and impair organ function. We describe the mechanisms of ectopic fat depositions in the liver, skeletal muscle, and in and around the heart and the consequences for each organs function. In addition, we systematically reviewed the literature for the effects of diet-induced weight loss and exercise on ectopic fat depositions.

Prolonged caloric restriction in obese T2DM patients decreases BMI and improves glucoregulation associated with decreased myocardial TG content and improved diastolic heart function. Therefore, myocardial TG stores in obese patients with T2DM are flexible and amendable to therapeutic intervention by caloric restriction.

The benefit of thyroid hormone therapy for subclinical hypothyroidism is uncertain. New evidence from recent large randomized clinical trials warrants an update of previous meta-analyses. OBJECTIVE To conduct a meta-analysis of the association of thyroid hormone therapy with quality of life and thyroid-related symptoms in adults with subclinical hypothyroidism.

Clinical questionWhat are the benefits and harms of thyroid hormones for adults with subclinical hypothyroidism (SCH)? This guideline was triggered by a recent systematic review of randomised controlled trials, which could alter practice.Current practiceCurrent guidelines tend to recommend thyroid hormones for adults with thyroid stimulating hormone (TSH) levels >10 mIU/L and for people with lower TSH values who are young, symptomatic, or have specific indications for prescribing.RecommendationThe guideline panel issues a strong recommendation against thyroid hormones in adults with SCH (elevated TSH levels and normal free T4 (thyroxine) levels). It does not apply to women who are trying to become pregnant or patients with TSH >20 mIU/L. It may not apply to patients with severe symptoms or young adults (such as those ≤30 years old).How this guideline was createdA guideline panel including patients, clinicians, and methodologists produced this recommendation in adherence with standards for trustworthy guidelines using the GRADE approach.The evidenceThe systematic review included 21 trials with 2192 participants. For adults with SCH, thyroid hormones consistently demonstrate no clinically relevant benefits for quality of life or thyroid related symptoms, including depressive symptoms, fatigue, and body mass index (moderate to high quality evidence). Thyroid hormones may have little or no effect on cardiovascular events or mortality (low quality evidence), but harms were measured in only one trial with few events at two years’ follow-up.Understanding the recommendationThe panel concluded that almost all adults with SCH would not benefit from treatment with thyroid hormones. Other factors in the strong recommendation include the burden of lifelong management and uncertainty on potential harms. Instead, clinicians should monitor the progression or resolution of the thyroid dysfunction in these adults. Recommendations are made actionable for clinicians and their patients through visual overviews. These provide the relative and absolute benefits and harms of thyroid hormones in multilayered evidence summaries and decision aids available in MAGIC (https://app.magicapp.org/) to support shared decisions and adaptation of this guideline.

No abstract