Higher Waist Hip Ratio Genetic Risk Score Is Associated with Reduced Weight Loss in Patients with Severe Obesity Completing a Meal Replacement Programme.

Background: A better understanding of the influence of genetic factors on the response to lifestyle interventions in people with obesity may allow the development of more personalised, effective and efficient therapeutic strategies. We sought to determine the influence of six obesity-related genetic risk scores on the magnitude of weight lost by patients with severe obesity who completed a dietary intervention. Methods: In this single-centre prospective cohort study, participants with severe and complicated obesity who completed a 24-week, milk-based meal replacement programme were genotyped to detect the frequency of common risk alleles for obesity and type 2 diabetes-related traits. Genetic risk scores (GRS) for six of these traits were derived. Participants with a potentially deleterious monogenic gene variant were excluded from the analysis. Results: In 93 patients completing the programme who were not carrying a known obesity-related gene mutation, 35.5% had diabetes, 53.8% were female, mean age was 51.4 ± 11 years, mean body mass index was 51.5 ± 8.7 and mean total weight loss percent at 24 weeks was 16 ± 6.3%. The waist-hip ratio (WHR) GRS was inversely associated with percentage total weight loss at 24 weeks (adjusted ß for one standard deviation increase in WHR GRS -11.6 [-23.0, -0.3], p = 0.045), and patients in the lowest tertile of WHR GRS lost more weight. Conclusions: Patients with severe and complicated obesity with a genetic predisposition to central fat accumulation had less weight loss in a 24-week milk-based meal replacement programme, but there was no evidence for influence from the five other obesity-related genetic risk scores on the response to dietary restriction.

Making weight: acute muscle weakness and hypokalaemia exacerbated by thyrotoxicosis factitia in a bodybuilder.

SUMMARY: A 32-year-old Caucasian male presented to the emergency department with a one-day history of acute severe bilateral lower limb weakness, three days after competing in a bodybuilding competition. He consumed large quantities of carbohydrate-rich foods following the competition. His past medical history was significant for anxiety, and family history was non-contributory. Examination was normal except for reduced power and hyporeflexia in both legs, despite his muscular physique. He was noted to have severe hypokalaemia (K+= 1.9 mmol/L). His thyroid function tests were consistent with thyrotoxicosis. He reported taking thyroxine and several other agents to facilitate muscle mass generation before the bodybuilding competition. His presentation was reminiscent of thyrotoxic periodic paralysis, albeit uncommon with Caucasian ethnicity. He also had transient hyperglycaemia at presentation with concomitant hyperinsulinaemia, which could be attributed to the carbohydrate load and may have exacerbated his hypokalaemia through a transcellular shift. Urine toxicology screen subsequently ruled out the use of diuretics but confirmed the presence of a long-acting beta agonist (clenbuterol) which, along with other substances, may have aggravated the hypokalaemia further. After 12 h of i.v. replacement, the potassium level normalised and leg weakness resolved. The patient agreed to stop taking thyroxine and beta agonists and was well during the clinic visit at one month follow-up. This case highlights the potential for thyrotoxicosis factitia to exacerbate hypokalaemia and muscle weakness from other causes in bodybuilders presenting with acute severe weakness, irrespective of ethnicity. LEARNING POINTS: In patients presenting with muscle weakness and hypokalaemia, early consideration of thyrotoxicosis is essential, even in the absence of a past history of thyroid disease or specific symptoms of thyrotoxicosis, in order to allow prompt initiation of appropriate treatment and to prevent recurrence. Bodybuilders may constitute a uniquely 'at-risk' group for thyrotoxic periodic paralysis secondary to thyrotoxicosis factitia, especially where there is concomitant use of beta-adrenergic agonists, even in the absence of diuretic use. Although rare and usually described in patients of Asian or Polynesian ethnicity, this case highlights that thyrotoxic periodic paralysis secondary to thyrotoxicosis factitia can also occur in patients with Caucasian ethnicity. We speculate that consuming large quantities of carbohydrates may induce hyperinsulinaemia, which could theoretically contribute to worse hypokalaemia, though mechanistic studies would be needed to explore this further.