Hormonal
Germline loss-of-function PTEN mutations cause constitutive insulin sensitivity, resulting in significantly lower fasting insulin levels and higher glucose disposal rates despite the presence of obesity.
This finding highlights that metabolic health (insulin sensitivity) is genetically regulated and can be preserved in obesity if specific pathways (like PTEN) are active. It suggests that BMI alone is an insufficient predictor of metabolic risk for all individuals, particularly those with specific genetic profiles.
Measures of insulin resistance were lower in the patients with a PTEN mutation than in controls (e.g., mean fasting plasma insulin level, 29 pmol per liter [range, 9 to 99] vs. 74 pmol per liter [range, 22 to 185]; P = 0.001). This finding was confirmed with the use of hyperinsulinemic euglycemic clamping, showing a glucose infusion rate among carriers 2 times that among controls (P = 0.009).
Why this rating
Small sample size (n=15) but high-quality measurement methods (hyperinsulinemic euglycemic clamp) and strong statistical significance.
Source
<i>PTEN</i> Mutations as a Cause of Constitutive Insulin Sensitivity and Obesity
Aparna Pal et al. · New England Journal of Medicine · 2012
DOI 10.1056/nejmoa1113966
More from this paper
Related findings · Hormonal
- Initial treatment for type 2 diabetes should be a combination of metformin and either an SGLT-2 inhibitor or a GLP-1 receptor agonist to achieve cardiorenal protection, rather than monotherapy or older agents like sulfonylureas.Strong
- For patients with specific monogenic obesity syndromes (leptin deficiency, POMC/PCSK1/LEPR mutations), targeted pharmacotherapy (recombinant leptin or setmelanotide) is highly effective and should be prioritized, unlike in polygenic obesity.Strong
- Continued weekly administration of 2.4 mg subcutaneous semaglutide prevents weight regain and promotes further weight loss in adults with overweight or obesity, whereas switching to placebo results in significant weight regain.Strong
This is one finding among thousands. Every one is graded and traced to its source, so you can see what the evidence actually supports. Browse the research →