the prevalence of prediabetes ( pd ) in poland is one of the highest in the world , about 16% of population is estimated to have impaired glucose tolerance ( igt ) , and by the year 2035 , the number of people with igt is projected to increase to about 19% . pd is the condition in which the patients have slight increase in blood glucose concentrations than the normal levels but they are not said to be diabetic . the diagnostic criteria for diagnosis of pd according american diabetes association ( ada ) are as follows : impaired fasting glucose ( ifg ) , igt , and/or glycated hemoglobin ( hba1c ) levels from 5.7 to 6.4% . pd status is considered as risk factor for the further development of diabetes mellitus type 2 ( t2 dm ) as well as cardiovascular disease ( cvd ) . subnormal testosterone concentrations in men with t2 dm , relative to reference ranges based on healthy young men ( < 12  nmol / l ) , are present in 2540% of patients [ 46 ] , but between aging , obese men , the prevalence of low t levels is around 50% . only a small proportion of these men will have classical hypogonadism because many of men with t2 dm have symptoms consistent with t deficiency , but such symptoms are nonspecific and overlap with comorbidities . the clinical symptoms most commonly associated with t deficiency are low libido and erectile dysfunction , decreased muscle mass and strength , increased body fat , decreased bone mineral density and osteoporosis , depressed mood , and fatigue [ 8 , 9 ] . hypogonadism may influence not only quality of life in men , but also life span . some observational studies show that t deficiency is associated with increased risk of all - cause and cvd - related mortality [ 10 , 11 ] . nmol / l in diabetic men may influence on the prevalence of obesity , but obesity may also result in t deficiency . there is evidence to suggest a bidirectional relationship of lowered t with increased visceral fat , which may promote a self - perpetuating cycle in diabetic men . most elderly men presenting pd also suffer from the metabolic syndrome ( mets ) , an insulin resistance syndrome with simultaneous occurrence of abdominal obesity , glucose metabolism disturbances , dyslipidemia , and hypertension . in our previous study we described that hypogonadism was diagnosed in 30% patients with pd in polish population   but the impact of this phenomenon on body composition is unknown as well as impact of other anabolic hormones , like dehydroepiandrosterone sulfate ( dheas ) and insulin - like factor 1 ( igf-1 ) . only few studies have demonstrated relationships between anabolic hormones and ifg   or pd   in men but they did not assess body composition . the aim of this study was to investigate the relationships between anabolic hormones and body composition in men with prediabetes . this study was performed in department of internal diseases , diabetology and endocrinology , medical university of warsaw , poland , in male patients attending the outpatient clinic for glucose metabolism disorders . the inclusion criteria were ( 1 ) a laboratory proved pd and ( 2 ) age of 4080 years . the exclusion criteria were as follows : ( 1 ) diabetes mellitus type 1 or 2 , ( 2 ) hypercortisolism , thyroid function disturbances , ( 3 ) recent or current t replacement , androgen deprivation therapy , or any hormonal treatment , either during the study or in history , ( 4 ) recent or current treatment , which may affect body composition , for example , metformin , and ( 5 ) lack of informed written consent . we recruited 196 consecutive patients with pd ( aged between 40 and 80 years ) and , as a control group , 184 men matched by age and with a fasting plasma glucose ( fpg ) less than 5.55  mmol / l ( 100  mg / dl ) and hba1c less than 5.7% . we qualified patients who underwent body composition measurements ( 84 patients with pd and 58 control men ) . this study was approved by the local research ethics committee and was conducted in accordance with declaration of helsinki ; informed consent was obtained from all participants . pd was diagnosed in patients with ifg from 100 to 125  mg / dl ( 5.66.9  mmol / l ) and two - hour glucose concentration in oral glucose tolerance test ( ogtt ) < 140  mg / dl ( < 7.8  mmol / l ) or in patients with igt two - hour glucose concentration in ogtt from 140 to 200  mg / dl ( 7.811.0  mmol / l ) or in patients with hba1c from 5.7% to 6.4% . the diagnosis of mets was based on the following criteria : waist circumference ( wc ) 94  cm and any two of the following : triglycerides  150  mg / dl , hdl - cholesterol < 40  mg / dl , blood pressure  130/85  mmhg , and fpg  100  mg / dl . height , weight , and waist circumference were measured and body mass index ( bmi ) was calculated . obesity was defined as a body mass index ( bmi ) of 30 or more . cardiovascular disease ( cvd ) hypertension was considered to be present if the participant reported having received the diagnosis or if he was receiving medication for the condition . fat mass and lean tissue were measured using a whole - body dual - energy x - ray absorptiometry ( dxa ) scanner ( lunar prodigy , ge medical systems , madison , wi , usa ; software version 11.4 ) . the international society for clinical densitometry recommends dxa as reference method in body composition studies and notes that this method may be useful for risk - stratification of obese patients . scanned images of the whole body were subdivided into head , trunk , and left and right arm and legs . the borders between subregions were a line under the chin , a line between the humeral head and the glenoid fossa , and a line at the level of the femoral necks . the abdominal area , which is characterized by a high content of visceral fat and a low content of subcutaneous fat on mri , was measured by dxa between vertebrae l2 and l4 . the coefficient of variation for measurements of body composition with this method is about 2% . we calculated also skeletal muscle mass index ( smi ( % ) = total skeletal muscle mass ( kg)/weight ( kg )  100 ) . sarcopenia was defined as an smi of 1 sd below the sex - specific mean value for the young reference group . in all patients with pd venous blood samples were obtained between 8.00 and 10.00 a.m. after centrifugation , the serum was collected and frozen at 70c until analysis . fpg was measured with enzymatic method using biosen 5040 analyzer ( ekf - diagnostic gmbh , germany ) and glycated hemoglobin ( hba1c ) with hplc method using variant analyzer ( bio - rad laboratories inc . , united states ) . hba1c values were expressed as % according to national glycohemoglobin standardization program ( ngsp ) . the serum levels of tt , dheas , estradiol ( e2 ) , and igf-1 were measured with immunometric assays ( immulite 2000 and ria cac ; siemens medical solution , malvern , pa , united states ) and expressed in nmol / l for tt , pg / ml for e2 , and ng / ml for dheas and igf-1 ( to convert the values for dheas to mol / l , multiply by 0.00271 ; igf-1 to nmol / l , multiply by 0.131 ; and e2 to pmol / l , multiply by 3.671 ) . to estimate the circulating fraction of ft we measured the serum level of sex hormone - binding globulin ( shbg ) using an immunoassay ( diagnostic products corp , san francisco , the serum level of calculated ( cft ) expressed in nmol / l was calculated with the validated equation of vermeulen et al . , according to the following formula : cft = t  n  s + ((n + s  t ) + 4nt)/2n , where t , s , and a are total testosterone ( nmol / l ) , shbg ( nmol / l ) , and albumin ( g / l ) concentrations ; n = 0.5217a + 1 , using the association constants of testosterone for shbg ( 10  l / mol ) and albumin ( 3.6  10  l / mol ) quoted by the authors . tt levels < 12  nmol / l and cft levels < 0.250  nmol / l were taken as low . most continuous variables had a normal distribution and were expressed as a mean  the standard deviation of the mean . serum dheas had a skewed distribution so they were log - transformed to normalize their distribution , expressed as a median with lower and upper quartiles , and the intergroup differences were tested using the t - test for unpaired samples for normalized values . categorized variables were expressed as a number and a percentage , and the intergroup differences were tested using the  test . to establish correlation spearman test was used to compare nonparametric data and pearson test to compare parametric data . all relationships were assessed by linear univariate and multivariate regression analysis to reduce bias in a cross - sectional study . in multivariate analysis , a total of 84 patients with pd , mean age 66.5  3.8 years , and 58 control men , mean age 65.7  3.8 years , were evaluated in this study . patients with pd had lower tt , cft , and dheas levels ( p < 0.001 , p < 0.005 , and p < 0.02 , resp . ) and higher e2 and shbg levels ( p < 0.05 and p < 0.02 , resp . ) . igf-1 , prolactin , and fsh did not differ between groups , while lh levels were significantly higher in patients with pd ( p < 0.05 ) . patients with pd had higher hba1c , fpg , and glucose levels in 2-hour ogtt than healthy men ( p < 0.02 , p < 0.001 , and p < 0.05 , resp . ) . also total - cholesterol , ldl - cholesterol , and triglycerides levels were statistically significant higher in patients with pd ( p < 0.05 , p < 0.02 , and p < 0.05 , resp . ) . systolic and diastolic blood pressure did not differ between groups ; prediabetic men presented with more common hypertension , obesity , mets , and cvd ( p < 0.05 , p < 0.02 , p < 0.01 , and p < 0.05 , resp . ) than control group but percentage of current smokers was similar in both groups ( table 1 ) . in patients with pd we have shown negative relationships between bmi and tt ( r = 0.3594 ; p < 0.01 ) , bmi and cft ( r = 0.3682 , p < 0.01 ) , wc and tt ( r = 0.3476 , p < 0.05 ) , and wc and cft ( r = 0.3623 ; p < 0.02 ) . there were also negative relationships between cft and hba1c ( r = 0.3734 ; p < 0.002 ) and cft and ldl - cholesterol ( r = 0.3679 , p < 0.02 ) while tt correlated significantly only with ldl - cholesterol ( r = 0.3438 , p < 0.05 ) . in control group we also observed negative relationships between bmi and tt ( r = 0.3346 ; p < 0.05 ) , bmi and cft ( r = 0.3428 ; p < 0.05 ) , and wc and cft ( r = 0.3478 ; p < 0.02 ) . there was also negative relationship between cft and hba1c ( r = 0.3538 ; p < 0.05 ) but in control group we did not observe significant relationships between androgens and lipids levels . in multivariate analysis these relationships were significant after adjustment for age and bmd . analysis of prediabetic patients also revealed that patients with igt had lower tt and cft levels than patients with ifg ( p < 0.02 ) . in multivariate analysis the difference between dheas and igf-1 levels did not differ significantly among prediabetic patients with ifg or igt ( table 2 ) . wc were significantly higher in patients with pd when compared with control group ( p < 0.01 ) while differences of weight and bmi were not statistically significant . we observed significant differences in body composition assessed by dxa methods between patients with pd and control men ( table 3 ) . we showed the higher total and abdominal fat mass in patient with pd compared with control men ( p < 0.02 and p < 0.01 , resp . ) as well as the lower total lean and abdominal lean mass in prediabetic patients ( p < 0.05 and p < 0.02 , resp . ) . the differences of trunk , arm , and leg fat mass as well as lean mass were not significant . we observed slightly lower smi in prediabetic men than in control group , but differences were not significant ( mean 40.2 versus 40.5 , resp . ) ( table 3 ) . analyses of relationships ( after adjustment for age and bmi ) between anabolic hormones , shbg , hba1c , and body composition are presented in table 4 . we have shown negative relationship between tt levels and total fat mass ( p = 0.014 ) and positive with abdominal lean mass ( p = 0.034 ) while cft levels were negatively associated with abdominal ( p = 0.02 ) , trunk ( p = 0.024 ) , and leg fat ( p = 0.037 ) as well as positively associated with total ( p = 0.022 ) and trunk lean mass ( p = 0.024 ) . dheas levels were negatively associated only with total fat ( p = 0.045 ) while igf-1 levels were positively associated with abdominal ( p = 0.003 ) and leg lean mass ( p = 0.015 ) . we observed also positive relationships between shbg and abdominal fat mass ( p = 0.024 ) and negative with total lean mass ( p = 0.002 ) . hba1c was positively associated with total fat mass ( p = 0.048 ) and negatively associated with total lean ( p = 0.014 ) and abdominal lean mass ( p = 0.034 ) . we showed negative relationship between tt levels and total fat mass ( r = 0.3421 ; p = 0.021 ) and positive with abdominal lean mass ( r = 0.3226 ; p = 0.038 ) while cft levels were negatively associated with abdominal fat ( r = 0.3523 ; p = 0.026 ) as well as positively associated with total lean mass ( r = 0.3345 ; p = 0.027 ) . we did not observe significant relationships between dheas , igf-1 , and hba1c , and parameters of body composition in control men ; however , shbg levels were negatively associated with total lean mass ( r = 0.3453 ; p = 0.02 ) . analysis of relationships between smi and anabolic hormones levels revealed that cft levels were positively associated with smi in prediabetic men ( r = 0.3465 ; p = 0.02 ) , while in control group we observed positive association smi with igf-1 levels ( r = 0.3265 ; p = 0.023 ) . we did not observe associations with dheas , tt , shbg , and hba1c in both groups . in this study we investigated the relationships between anabolic hormones and body composition in 84 men with pd from 40 to 80 years old and in 58 control aged - matched men . to achieve the goals , we have used dual - energy x - ray absorptiometry ( dxa ) method . in our opinion , there are two major findings arising from the present study . firstly , patients with pd had lower tt , cft , and dheas and higher e2 and shbg levels than those observed in control men but igf-1 levels did not differ between groups . in men with pd we observed negative relationships between bmi , wc , and tt as well as these results are consistent with our previous observations   that , not only in men with t2 dm but also among prediabetic man , the lower anabolic hormones than in healthy - peers , especially lower t levels , may by associated with glucose metabolism disorders . it seemed to us also clear that lower anabolic hormones may adversely affect body composition . secondly , we showed the higher total and abdominal fat mass in patient with pd compared with control group as well as the lower total lean and abdominal lean mass . we have also observed negative relationship between tt levels and total fat mass and positive with abdominal lean mass while cft levels were negatively associated with abdominal , trunk , and leg fat mass and positively associated with total and trunk lean mass . in contrast , dhea levels were negatively associated only with total fat while igf-1 levels were positively associated with abdominal and leg lean mass . in our cohort shbg showed positive correlation with abdominal fat mass and negative with total lean mass , while hba1c was positively associated with total fat mass and negatively associated with total lean and abdominal lean mas . these results suggest that anabolic hormones have probably significant influence on body composition in patients with pd but in various regions of the body these effects are not homogenic . our observations allow us to conclude that lower t most affects the abdominal obesity but dhea and igf-1 also are involved in body composition rearrangement in patients with pd . generally , it should be noted that patients with lower levels of tt , cft , dheas , and igf-1 have a tendency to obesity and reduced muscle mass . however , it must be pointed that , in our cohort , skeletal muscle mass index ( smi ) , which reflects the sarcopenia , the clinical status as well as prediabetes associated with insulin resistance , was only slightly lower in patients with pd . it seems , therefore , that in prediabetic men lowered anabolic hormones are associated mainly with an increase of fat mass . the prevalence of pd in poland is one of the highest in the world , so any consequences of pd are a serious public health problem . we have shown previously that low t was diagnosed in 30% of patients with pd and only in 14% of control group . we also observed that low tt levels in these patients were associated with clinical signs and symptoms of hypogonadism , erectile dysfunctions , lower urinary tract symptoms , depression , and a significant deterioration in the quality of life [ 22 , 23 ] . our knowledge about the influence of anabolic hormones , especially dheas and igf-1 , on metabolism and body composition in patients with pd is limited . ho et al .   demonstrated that pd was associated with an increased risk of subnormal tt levels compared to healthy individuals ( age - adjusted or = 1.87 ; 95% ci ) , still significant after adjusting for age , bmi , and mets . in mest study colangelo et al .   showed that ifg was associated inversely with tt , dheas , and e2 , and these correlations were still significant after adjustment for age and bmi . corona et al .   in men with sexual dysfunction showed that 19% of them were classified as ifg and these men more often had severe erectile dysfunction or hypogonadism when compared with normoglycemic men . .   showed that igf1 levels in the low - normal range are associated with ifg in men , and kameda et al . observed association of low dheas levels with the progression of pd to t2 dm in men . these results have suggested that dheas and igf-1 also play an important role in glucose metabolism , but their influence on body composition in men with pd is still unknown . because there are no studies in men with pd , our knowledge about relationships between anabolic hormones and body composition is partially based on studies conducted in men with t2 dm . in our cohort we previously showed that tt levels below 12  nmol / l were observed in 30% of prediabetic men in contrast to 14% in control group , while in current study we observed that androgens were negatively associated with fat mass and positively with lean body mass , independent of age and bmi . these results are consistent with data suggesting that obesity is a major correlate of lowered tt in men with glucose metabolism disorders . it also demonstrates that adiposity is a major determinant of lowered tt , irrespective of whether men have t2 dm or  only  pd . whether lowered androgens are a cause or consequence of obesity can not be answered on the basis of our studies but current evidence suggests that this relationship is bidirectional : on the one hand , lower t leads to metabolically unfavorable changes in body composition , like decreasing of lean body mass and increasing of fat mass , with associated increases in insulin resistance . on the other hand , weight gain and development of t2 dm contribute to the age - related decline in tt levels however , weight loss increases tt levels , suggesting that this phenomenon is functional , and to a reversible degree . the possible pathophysiological mechanism between pd and lowered t is probably multifactorial and represented mainly by visceral adiposity and insulin resistance . decreased tt levels in men are associated with insulin resistance and reduced insulin sensitivity   and have been found to predict insulin resistance , obesity , and t2 dm . testosterone can be converted to estradiol in the adipose tissue and it has been suggested that excessive estrogens synthesis in the obese men may suppress secretion of t . in our study estradiol levels the studies in animals and in men after androgen deprivation therapy which suppress functions of androgen / androgen receptor ( ar ) signaling revealed significant metabolic disorders like t2 dm and mets which can be associated with tissue - specific ar signaling that is involved in regulation of metabolism . recent studies also shown that nucleotide polymorphism of the endothelial nitric oxide synthase ( enos ) gene may be an independent risk factor for t2 dm and insulin resistance in men with low t . diabetic men with lowered t are significantly more likely to be obese or insulin resistant ; however , the inverse association of low t with mets or t2 dm is less consistent for cft compared with tt . this is because of the confounding effects of shbg , itself being a strong associate of insulin resistance , and because shbg but not t was inversely associated with worse glycaemic control [ 7 , 12 ] . in our cohort we also demonstrated the higher shbg levels in prediabetic patients , positive relationships between shbg and abdominal fat mass , and negative with total lean mass . shbg probably may have biological actions beyond serving as a carrier protein for and regulator of circulating sex steroids . nmol / l , a threshold level that characterizes men with severe late onset hypogonadism and is required for t replacement therapy , but reduction in tt levels below 12  nmol / l was observed in about 25% patients . evidence derived from clinical studies supports the use of t replacement in hypogonadal patients , although the benefit - risk ratio is uncertain in advanced age . replacement therapy in diabetic men with lowered t may improve insulin sensitivity , glycemic control , cardiovascular risk factors , and diabetic complications [ 3538 ] but long - term influence of t in men with hypogonadism and pd is still unknown . it should be noted that in our study pd was diagnosed also in patients with hba1c from 5.7 to 6.4% . currently , an intermediate hba1c range is not considered as pd by the world health organization ; however , ada definition probably gives wider range of subjects at the risk group of t2 dm development , and hba1c of 5.76.4% detects , in part , different individuals with intermediate hyperglycemia compared with ifg and igt . it is also important to remember that we focused only on associations between body composition and hormones in men with pd . our model in no way established a causal link between anabolic hormones levels and pd as well as body composition . these conditions might simply overlap and they have probably separate pathophysiologic pathways . we must also note that muscle is a primary target organ for insulin action , but in our study we did not measure insulin concentration , and that is why we did not evaluate the relationships between insulin and anabolic hormones , and in our cross - sectional study we did not evaluate the potential impact of exercise and physical activity on the body composition . in conclusion , further studies are needed to establish whether the androgen replacement therapy would be beneficial in men with pd .
the influence of anabolic hormones and body composition in men with prediabetes ( pd ) is unknown . in a cross - sectional study we investigated the relationships between total testosterone ( tt ) , calculated free testosterone ( cft ) , dehydroepiandrosterone sulfate ( dheas ) , and insulin - like growth factor 1 ( igf-1 ) and body composition assessed using dual - energy x - ray absorptiometry ( dxa ) method in 84 patients with pd ( 4080 years ) and 56 men in control group . 
 patients with pd had lower tt , cft , and dheas levels but similar igf-1 levels in both groups . 
 patients with pd presented the higher total and abdominal fat as well as the lower total and abdominal lean than control ( p < 0.02 , p < 0.01 , p < 0.05 , and p < 0.02 , resp . ) . we observed negative relationship between tt and total fat ( p = 0.014 ) and positive with abdominal lean mass ( p = 0.034 ) , while cft was negatively associated with abdominal ( p = 0.02 ) , trunk ( p = 0.024 ) , and leg fat ( p = 0.037 ) and positively associated with total ( p = 0.022 ) and trunk lean ( p = 0.024 ) . 
 dheas were negatively associated with total fat ( p = 0.045 ) , and igf-1 were positively associated with abdominal ( p = 0.003 ) and leg lean ( p = 0.015 ) . in conclusion , 
 the lowered anabolic hormones are involved in body composition rearrangement in men with pd . 
 further studies are needed to establish whether the androgen replacement therapy would be beneficial in men with pd .