Genetic research finds certain level of lifelong insulin resistance may have beneficial effects without increasing the risk of type 2 diabetes<\/p>\n
Certain levels of insulin resistance may sometimes lead to improvements in health, including lower cholesterol and healthy liver function, a new study has found.<\/p>\n
While insulin resistance is strongly linked to metabolic diseases such as type 2 diabetes (T2D), the research found that a level of lifelong insulin resistance does not necessarily increase the risk of T2D or other negative health outcomes.<\/p>\n
In fact, the analysis of model organisms suggests that reducing the activity of the insulin receptor \u2013 the protein that enables cells to respond to insulin and thereby induce insulin resistance \u2013 can sometimes produce beneficial effects, including healthier ageing.<\/p>\n
For this UK-based study, researchers studied individuals carrying rare damaging genetic variants in the insulin receptor gene (INSR) as a human model of insulin resistance.<\/p>\n
They analysed whole-genome sequencing data from 458,784 genetically inferred European ancestry participants in the UK Biobank, identifying 524 carriers of predicted damaging INSR missense variants (the variant that can naturally cause insulin resistance). They then compared the health and metabolic characteristics of people carrying these variants with those who did not.<\/p>\n
Their results showed that carriers of the damaging INSR variants exhibited mild hyperinsulinaemia (high levels of blood insulin relative to levels of blood glucose). This result is consistent with partial reduction of insulin receptor signalling (and thus insulin resistance).<\/p>\n
Despite this, these patients with the INSR variants displayed a paradoxically favourable metabolic profile, including lower blood fats, lower LDL (bad) cholesterol, liver enzymes, and waist-hip ratio, and higher (good) HDL cholesterol, with no difference in body mass index (BMI). These benefits were observed across the BMI distribution.<\/p>\n
INSR missense carriers also showed no excess risk of all-cause mortality, diabetes, cardiovascular disease, or malignancy in the UK Biobank \u2013 all of which would be typically expected in people with insulin resistance.<\/p>\n
The study, led by Jacques Murray Leech and Associate Professor Kashyap Patel of the University of Exeter, will be presented at the Annual Meeting of The European Association for the Study of Diabetes (EASD), taking place in Milan, Italy from September 28 to October 2.<\/p>\n
The authors conclude: \u201cThese findings provide the first human genetic evidence that mild, lifelong reduction in insulin signalling is associated with a healthier metabolic profile, distinct from classical insulin resistance. This suggests that not all forms of insulin resistance are uniformly bad news for health and offers insight into a potential resolution of this longstanding paradox.\u201d<\/p>\n
In future work the researchers plan to investigate why different forms of insulin resistance have different effects on health, including factors that may protect against cardiometabolic disease and whether other beneficial subtypes exist. These findings could help identify new pathways involved in metabolic health and potential targets for future research and treatments.<\/p>\n","protected":false},"excerpt":{"rendered":"Genetic research finds certain level of lifelong insulin resistance may have beneficial effects without increasing the risk of…\n","protected":false},"author":2,"featured_media":643155,"comment_status":"","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"footnotes":"","_share_on_mastodon":"0"},"categories":[78],"tags":[2675,18,135,19,19642,272094,6527,17,12209,6426],"class_list":["post-643154","post","type-post","status-publish","format-standard","has-post-thumbnail","category-health","tag-diabetes","tag-eire","tag-health","tag-ie","tag-insulin","tag-insulin-receptor","tag-insulin-resistance","tag-ireland","tag-liver","tag-type-2-diabetes"],"share_on_mastodon":{"url":"https:\/\/pubeurope.com\/@ie\/117115371545349227","error":""},"_links":{"self":[{"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/posts\/643154","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/comments?post=643154"}],"version-history":[{"count":0,"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/posts\/643154\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/media\/643155"}],"wp:attachment":[{"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/media?parent=643154"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/categories?post=643154"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/tags?post=643154"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}