although eating habits , lifestyle , genetics and emotional concerns are main factors involved in obesity etiopathogenesis , some medical conditions may also cause weight gain . insulin resistance ( ir ) , leptin resistance ( lr ) and polycystic ovary syndrome ( pcos ) commonly coexist with obesity . pcos is a common endocrine disorder affecting 621% of women of reproductive age , and about 50% of pcos patients are obese . in most cases , pcos can thus lead to increased risk of developing type 2 diabetes mellitus and cardiovascular disease in patients . adipose tissue is not only considered the main energy reservoir but also a pivotal endocrine organ involved in the regulation of many physiological processes , by secreting a variety of bioactive cytokines , such as leptin . leptin is involved in the regulation of food intake , energy balance , and body weight . as leptin is primarily secreted by adipose tissue and also has activity at an ovarian level , it is interesting to know whether serum leptin levels are correlated with ir in pcos . however , this correlation is still a matter of debate and further research is required to clarify the relationship between leptin , ir in pcos . while there is currently no medical treatment for lr , ir and pcos are often successfully treated with the use of insulin - lowering agents ( isds ) , the case of a 27-year - old morbidly obese woman suffering from concomitant ir , lr , pcos , and unresponsive to isds , treated with sg is here reported . in 2011 , a 27-year - old italian female with a body mass index ( bmi ) of 49.9  kg / m ( weight  =  141  kg ; height  =  168  cm ) was referred for bariatric surgery intervention for obesity . patient clinical history was also characterized by unresponsiveness to isds ( metformin , and thiazolidinedione ) even at maximum dose . the patient also reported that she stopped high doses of prescribed pharmacotherapy on several occasions due to side effects ( abdominal discomfort , cramping , diarrhoea and nausea ) . despite strict adherence to several exercise - associated diet programs , extremely aggressive diets , such as ketogenic enteral nutrition , and drugs for obesity treatment , the patient had continued to gain weight . over the past two years , her plasma insulin levels were 2136  iu / ml ( normal range 629  iu / ml ) and plasma leptin levels were 89130  ng / ml ( normal range 0.512.7  ng / ml ) . in 2009 , the patient was treated with a 6-month placement of intragastric balloon . in six months the patient lost 21  kg ( from 131  kg to 110  kg ) with a concomitant improvement of both ir , lr , and pcos indicating , as reported in the literature , weight loss has a pivotal role in the etiopathogenesis of both ir and lr , and improved menstrual frequency . unfortunately , although weight loss and lifestyle modifications are the first line treatment in pcos , ir , and lr , they are associated with low adherence and sustainability over time . therefore , the patient completely regained this weight loss three months after the balloon was removed , with a concomitant deterioration of both ir and lr . after considering overall clinical history and a careful preoperative multidisciplinary clinical screening , patient s clinical characteristics before surgery ( baseline ) are reported in table 1 and fig . 1a , and clearly show high levels of hyperinsulinemia , hyperleptinemia , ir ( homa index 11.9 vs normal range 0.232.5 ) , dyslipidaemia , enlarged liver associated with high levels of transaminases , pcos , and amenorrhea . the patient then underwent a laparoscopic sleeve gastrectomy ( lsg ) for correction of her obesity . during the operation a routine upper gastrointestinal gastrografin swallow study was performed and showed no evidence of leak or obstruction . after discharge on the fifth postoperative day , the patient assumed a liquid diet that was changed to puree - based after 15 days , and after four additional weeks , to soft solid food . the patient was also instructed to regularly follow an enriched protein diet , to take daily vitamin supplements , and physical activity was encouraged . obviously , the surgery goals were to decrease total body weight and improve lipid and haepatic profile , ir , lr , and consequently the pcos . patient presence at scheduled follow - up visits ( 6 , 12 , 24 and 36 months ) was 100% . in particular , the patient lost 35.3  kg six months after surgery , and 49.6  kg , 66.7  kg and 71.6  kg , at 12 , 24 and 36 months after the surgery , respectively . at postoperative month 36 , bmi was 23.4  kg / m that on the basis of bmi categories is considered a healthy weight . more importantly , patient levels of insulin and leptin started to improve at postoperative month 6 to become normal at postoperative month 24 . at postoperative month 36 , plasma insulin and leptin levels were 2.9  iu / ml and 1.9  ng / ml , respectively , for insulin and leptin range values ( table 1 ) this is considered normal . furthermore , as shown in fig . 1 , patient s ovaries that at baseline ( a ) had characteristic aspects related to pcos , at postoperative month 36 ( b ) may be defined as normal . in fact , the patient reported that starting from postoperative month 12 her menstrual cycle became regular with a frequency range of 2731 days . patients become lr by the same mechanism associated with ir , through a continuous overexposure to high levels of hormone , , . over time , if the body is exposed to excess leptin , it will become resistant , just as it can become resistant to insulin . while there is currently no medical treatment for lr , ir is often successfully treated with the use of insulin - lowering agents or isds . infact , the recognition of ir as a principal factor in the pathogenesis of pcos has led to the use of isds for pcos treatment . for instance , troglitazone is a drug that improves ir and hyperinsulinemia without altering leptin levels . by contrast , metformin , an insulin sensitizer widely used for treating type 2 diabetes mellitus , considerably reduces serum leptin concentration in obese and non - obese pcos patients . however , some women are unresponsive to this type of pharmacotherapy . to our knowledge , only one case of a 16-year - old caucasian male with lr and successfully treated with bariatric surgery has been reported in the medical literature . to our knowledge , this is the first report of bariatric surgery in a morbidly obese patient suffering from concomitant ir , lr , pcos , and unresponsive to isds . bariatric surgical procedures , such as sg , are currently the most effective therapy for the treatment of obesity . in the present report , sg was applied to resolve an intricate endocrinological framework confirming its therapeutic value not only in effectively determining weight loss but also as endocrine / metabolic surgery able to treat multifactorial endocrinopathy . the underlying molecular mechanisms contributing to these benefits remain largely undetermined , despite offering tremendous potential to reveal new targets for therapeutic intervention , mostly in those patients unresponsive to classical pharmacotherapy . written informed consent was obtained from the patient for publication of this case report and accompanying images . a copy of the written consent is available for review by the editor - in - chief of this journal on request . the authors of this manuscript declare no conflict of interest regarding any commercial label or pharmaceutical industry .
highlightsinsulin resistance ( ir ) and leptine resistance ( lr ) commonly coexist with obesity.polycystic ovary syndrome ( pcos ) is often associated with obesity.there is currently no medical treatment for lr.ir and pcos are often successfully treated with the use of insulin - lowering agents.some women are poorly responsive or intolerant to insulin - lowering agents .