sarcopenia is characterized by loss of skeletal muscle mass and its function1 , 2 , and is associated with aging1 . the prevalence rates of sarcopenia in people aged 6574 years are 2.3% in men and 5.0% in women , whereas those in people aged 7584 years are 15.3% in men and 11.7% in women in a healthy japanese population3 . sarcopenia has recently been recognized as one of the complications of type 2 diabetes4 , 5 . however , there have been no reports on the prevalence of sarcopenia in patients with type 1 diabetes . advanced glycation endproducts ( ages ) , the products of nonenzymatic binding of glucose and proteins , accumulate in various tissues in older adults6 . chronic hyperglycemia accelerates the ages accumulation , and increases the risk of diabetic vascular complications , such as macroangiopathy and microangiopathy7 , 8 , 9 , 10 , 11 . a previous study suggested that hyperglycemia was associated with lower muscle function in middleaged and older patients12 . however , there have been no reports on the relationship between the accumulation of ages in patients with type 1 diabetes and a reduction of muscle function . skin autofluorescence ( af ) has been proposed as a marker of ages accumulation in the skin13 . skin af is strongly correlated with the specific ages content in skin biopsies , as shown in multiple validation studies14 , 15 , 16 , 17 . the aim of the present study was to ascertain the status of sarcopenia , and compare it with clinical characteristics in japanese patients with type 1 diabetes . the present study was approved by the ethical committee of tokushima university hospital ( approved # 22811 ) . the inclusion criteria of this study were outpatients with type 1 diabetes aged over 40 years at tokushima university hospital . patients who were taking steroids and those with myopathy , severe peripheral neuropathy or motor function disorders were excluded . a crosssectional analysis was carried out for each set of data obtained from july until october 2015 . there were 36 participants , aged 4275 years ( men n = 9 , women n = 27 ; mean age 55.7  10.3 years ( mean  sd ) ; duration of disease 13.9  10.2 years ) . skeletal muscle mass was measured with a body composition analyzer ( in body bioelectrical impedance analyzer ; bio space , seoul , korea ) using multifrequency bioelectrical impedance analysis . skeletal muscle mass index ( smi ) was calculated by dividing extremity skeletal muscle by height squared . a previous validation study showed that lean body mass evaluated by this device was highly correlated with the data measured by dualenergy xray absorptiometry ( intraclass correlation coefficient : men = 0.96 and women = 0.95 , respectively)18 . grip strength and knee extension strength were measured using handheld dynamometers ( t.k.k5401 ; takei scientific instruments , tokyo , japan ; and tus f100 ; anima , tokyo , japan ) . a previous validation study showed that interrater reliability of isometric knee extension strength measurements was highly correlated with the data measured by the handheld dynamometers ( intraclass correlation coefficient : men and women = 0.99 , respectively)19 . gait speed was measured using a stopwatch in time units of 0.01 s. participants were asked to walk straight ahead for 11 m at their usual walking speed . the walking speed was measured at the middle 5 m. measurements were carried out twice and the faster speed ( m / s ) was recorded20 . muscle morphology and physical functional parameters were applied to the asian working group for sarcopenia diagnostic algorithm to identify sarcopenia20 . the cutoff values for sarcopenia were smi < 7.0 and < 5.7 kg / m for men and women , respectively , grip strength < 26 and < 18 kg for men and women , respectively , and gait speed < 0.8 m / s . also , the cutoff value that shows a low value for lower limb muscle strength was set as < 0.3 kg / kg of body weight ( kg / kgbw ) for both men and women20 , 21 , 22 . skin af was measured with the age reader ( diagnoptics technologies bv , groningen , the netherlands ) , a device that estimates ages skin accumulation using ages fluorescent properties13 . a previous study showed that repeated skin af measurements on 1 day show an overall altman error rate of 5.03%14 . spss statistics 22 ( ibm japan , tokyo , japan ) was used for statistical processing . relationships among age , diabetes duration , skin af , hba1c , smi and physical function parameters were determined using the pearson 's correlation coefficient . the present study was approved by the ethical committee of tokushima university hospital ( approved # 22811 ) . the inclusion criteria of this study were outpatients with type 1 diabetes aged over 40 years at tokushima university hospital . patients who were taking steroids and those with myopathy , severe peripheral neuropathy or motor function disorders were excluded . a crosssectional analysis was carried out for each set of data obtained from july until october 2015 . there were 36 participants , aged 4275 years ( men n = 9 , women n = 27 ; mean age 55.7  10.3 years ( mean  sd ) ; duration of disease 13.9  10.2 years ) . skeletal muscle mass was measured with a body composition analyzer ( in body bioelectrical impedance analyzer ; bio space , seoul , korea ) using multifrequency bioelectrical impedance analysis . skeletal muscle mass index ( smi ) was calculated by dividing extremity skeletal muscle by height squared . a previous validation study showed that lean body mass evaluated by this device was highly correlated with the data measured by dualenergy xray absorptiometry ( intraclass correlation coefficient : men = 0.96 and women = 0.95 , respectively)18 . grip strength and knee extension strength were measured using handheld dynamometers ( t.k.k5401 ; takei scientific instruments , tokyo , japan ; and tus f100 ; anima , tokyo , japan ) . a previous validation study showed that interrater reliability of isometric knee extension strength measurements was highly correlated with the data measured by the handheld dynamometers ( intraclass correlation coefficient : men and women = 0.99 , respectively)19 . gait speed was measured using a stopwatch in time units of 0.01 s. participants were asked to walk straight ahead for 11 m at their usual walking speed . the walking speed was measured at the middle 5 m. measurements were carried out twice and the faster speed ( m / s ) was recorded20 . muscle morphology and physical functional parameters were applied to the asian working group for sarcopenia diagnostic algorithm to identify sarcopenia20 . the cutoff values for sarcopenia were smi < 7.0 and < 5.7 kg / m for men and women , respectively , grip strength < 26 and < 18 kg for men and women , respectively , and gait speed < 0.8 m / s . also , the cutoff value that shows a low value for lower limb muscle strength was set as < 0.3 kg / kg of body weight ( kg / kgbw ) for both men and women20 , 21 , 22 . skin af was measured with the age reader ( diagnoptics technologies bv , groningen , the netherlands ) , a device that estimates ages skin accumulation using ages fluorescent properties13 . a previous study showed that repeated skin af measurements on 1 day show an overall altman error rate of 5.03%14 . spss statistics 22 ( ibm japan , tokyo , japan ) was used for statistical processing . relationships among age , diabetes duration , skin af , hba1c , smi and physical function parameters were determined using the pearson 's correlation coefficient . the presence of hypertension , smi and grip strength were significantly lower in women than in men . of the patients with type 1 diabetes , 16.6% ( men 0.0% , women 22.2% ) were diagnosed as sarcopenia according to the asian working group for sarcopenia criteria19 ( table 2 ) . the prevalence of smi , grip strength , gait speed and lower limb strength below the cutoff value was 16.6% ( men 0.0% , women 22.2% ) , 25.0% ( men 11.1% , women 29.6% ) 8.3% ( men 0.0% , women 11.1% ) and 47.2% ( men 22.2% , women 55.6% ) , respectively . characteristics of type 1 diabetes patients data are shown as mean value  sd . pvalue for sex difference : * p < 0.05 , * * p < 0.01 , * * * p < 0.001 . ace , angiotensinconverting enzyme ; af , autofluorescence ; arb , angiotensin ii receptor blocker ; bmi , body mass index ; bw , bodyweight ; csii , continuous subcutaneous insulin infusion ; egfr , estimated glomerular filtration rate ; hba1c , glycated hemoglobin ; mdi , multiple daily injections ; ndr , nondiabetic retinopathy ; pdr , proliferative diabetic retinopathy ; ppdr , preproliferative diabetic retinopathy ; sdr , simple diabetic retinopathy ; smi , skeletal muscle mass index . prevalence of sarcopenia and cutoff value parameters smi , skeletal muscle mass index . there was no significant correlation between knee extension strength and smi . knee extension strength was negatively correlated with duration of diabetes ( r = 0.16 , p < 0.05 ) and skin af ( r = 0.14 , p < 0.05 ) , but not with hba1c ( figure 1 ) . smi was negatively correlated with age ( r = 0.17 , p = 0.01 ) , but not hba1c , skin af or duration of diabetes . multiple regression analyses were carried out using knee extension strength / weight and smi indices as dependent variables , and age , estimated glomerular filtration rate , dyslipidemia , hypertension , neuropathy , retinopathy , cardiovascular disease and skin af as independent variables . skin af was negatively associated with knee extension strength / weight (  = 0.37 , p = 0.03 ) . the correlation between knee extension strength / weight , skeletal muscle mass index ( smi ) and clinical characteristics . ( a , b ) age , ( c , d ) duration of diabetes , ( e , f ) glycated hemoglobin ( hba1c ) and ( g , h ) skin autofluorescence ( af ) in male ( open circle ) and female ( closed circle ) patients with type 1 diabetes . the aim of the present study was to investigate the prevalence rate of sarcopenia in patients with type 1 diabetes , and to validate the relationship between ages accumulation and reduced muscle function . compared with the previous report by yuki et al.3 , the prevalence of sarcopenia in patients with type 1 diabetes in the present study , where the mean age was 55.7  10.3 years , was unexpectedly higher , and the proportion of women was markedly higher . furthermore , the percentage of participants whose grip strength values were below the cutoff values was higher than that found by yuki et al.3 in addition , the prevalence of participants whose knee extension strength was less than the cutoff value was very high ( 47.2% ) . muscle mass has been reported to correlate with muscle function in healthy individuals23 , 24 . however , there was no significant correlation between knee extension strength and smi in the present study . this possibility suggests that muscle function is impaired independently from agerelated reduction of muscle mass in patients with type 1 diabetes . in contrast , skin af and the duration of disease had a significant negative correlation with knee extension strength . previous reports have shown that the accumulation of ages in fast twitch muscle fibers crosslinks muscle collagen , hardens muscle stiffness and reduces the tonic force of muscle contraction25 , 26 , 27 . several studies suggested that muscle function declined with accumulation of ages in patients with type 2 diabetes mellitus28 , and healthy middleaged29 and older people30 . sugisawa et al.31 reported that skin af reflects integration of past longterm glycemic control in patients with type 1 diabetes . taken together , the results of the present study suggest that sustained hyperglycemia associated with long duration of disease and accumulation of ages could be involved as a mechanism in the impaired muscle function together with aging in patients with type 1 diabetes . however , there was no correlation between smi and skin af . because a significant negative correlation between the smi and age was observed , skin af was not associated with lower muscle mass in patients with type 1 diabetes . skin af and age were independent factors for knee extension strength / weight and smi , respectively . the limitations of the present study were that the study design was crosssectional without control subjects , so we were not able to achieve detailed verification of sarcopenia incidence , along with muscular dysfunction and the influence of ages accumulation in the muscular tissue of type 1 diabetes patients . we were also unable to evaluate the influence of lifestyle , diabetic complications ( such as neuropathy ) and pharmacotherapy of patients with type 1 diabetes on the decline of muscle strength . finally , another limitation was the small sample size of the analyzed participants in the present study . in conclusion , the present study shows that the prevalence rate of lower limb muscular dysfunction was higher than sarcopenia in japanese patients with type 1 diabetes . the ages accumulation might be one of the reasons for impaired lower limb muscle function in these patients .
abstractaccumulation of advanced glycation endproducts ( ages ) is thought to contribute to muscle weakness in a diabetic animal model . 
 skin autofluorescence is a proposed marker for accumulation of ages in the skin . 
 we aimed to investigate the relationship between ages accumulation , sarcopenia and muscle function of japanese patients with type 1 diabetes . 
 a total of 36 patients with type 1 diabetes participated in the present crosssectional study . 
 sarcopenia parameters ( skeletal muscle mass index and knee extension strength ) were compared with subcutaneous ages accumulation using skin autofluorescence . 
 the prevalence of sarcopenia and impaired knee extension strength was 16.6% ( men 0.0% , women 22.2% ) and 47.2% ( men 22.2% , women 55.6% ) , respectively . 
 knee extension strength was negatively correlated with skin autofluorescence ( r = 0.14 , p < 0.05 ) , but not with skeletal muscle mass index . in conclusion , the ages accumulation might be one of the reasons of impaired lower limb muscle function in japanese patients with type 1 diabetes .