diabetic ketoacidosis ( dka ) and diabetic ketosis ( dk ) are common and serious complications of diabetes mellitus . however , increasing evidence indicates that dka and dk are also common features of ketosis - prone type 2 diabetes ( t2d ) . in addition , patients with t2d are susceptible to dka under stressful and infectious conditions . dka in patients with t2d is a more severe disease , with worse outcomes , compared with concomitant dka and t1d . delays in the diagnosis and treatment of dka can lead to increased risks of advanced complications and 30-day mortality . previous studies in the field of dka have paid much attention to proinflammatory cytokines , whereas clinical parameters of liver and kidney function have not been well characterized [ 4 , 5 ] . tests of hepatic function include assessments of albumin , prealbumin , bilirubin , and enzyme levels . increased levels of aspartate aminotransferase ( ast ) , alanine aminotransferase ( alt ) , and -glutamyl transferase ( ggt ) are associated with t2d incidence [ 6 , 7 ] . these parameters are routinely detected in diabetic emergencies but do not receive attention from clinicians . elevations of serum creatinine , uric acid , and potassium levels have been observed in patients with dka [ 8 , 9 ] . the influence of dka and dk on liver and kidney function - related variables has not been well characterized and is thus poorly understood . prealbumin , a marker for protein malnutrition , has been advocated as a useful marker for predicting gastric surgery complications , cardiovascular outcome , and mortality in diabetic hemodialysis patients [ 10 , 11 ] . to our knowledge , there is no available study on the patterns or prognostic value of prealbumin levels in patients with dka and dk . accordingly , we aimed to evaluate changes in prealbumin levels and their diagnostic value in reflecting the severity of hyperglycemic emergencies . it should be stressed that previous studies only provided limited information and did not characterize the correlation with hyperglycemic crises [ 5 , 10 , 11 ] . the current study was performed due to limitations of the existing data in the literature . in particular , this study addressed whether kidney function increases or hepatic function decreases . the detection of kidney - liver function parameters will be helpful not only for early assessment but also for determining the prognosis of diabetes mellitus with hyperglycemic crisis . this study was performed in the endocrinology and emergency departments of two medical college - affiliated hospitals from october 2012 to march 2013 in accordance with the principles of the declaration of helsinki ( 2001 ) . ethical approval was obtained from the ethical committees of xuzhou medical college and nanchang university . a total of 40 consecutive patients with dka ( dka group ) , 40 patients with dk ( dk group ) , 40 diabetic patients in stable condition ( non - dk group ) , and 40 normal control subjects ( control group ) participated in the study ( table 1 ) . mmol / l , a urine ketone level defined as moderate to high ( + to + + + ) , and an arterial ph value < 7.30 at the time of admission . the criteria for dka severity were as follows , as previously described : mild , 7.20  ph < 7.30 ; moderate , 7.10  ph < 7.20 ; and severe , ph < 7.10 [ 4 , 12 , 13 ] . none of the subjects had heart failure , hematologic disease , or liver or kidney dysfunction . their previous liver or kidney dysfunctions were within normal range , and none of the patients were taking steroids . the dka , dk , and non - dk patients received medical treatment in the form of nutrition , oral hypoglycemic agents , and insulin therapy . blood samples from the control and non - dk groups were collected into vacutainer tubes by venipuncture after an overnight fast . in the dka and dk groups , the blood samples were drawn both at admission , before the initial therapy , and at the time of discharge from the hospital . laboratory tests , including routine biochemistry tests , were performed using routine laboratory methods for such serum parameters as albumin , alt , ast , bilirubin , creatinine , prealbumin , and uric acid levels . blood samples were collected into tubes for kidney - liver function tests and immediately processed using an olympus au 2700 autoanalyzer ( olympus , tokyo , japan ) . arterial gas analyses were performed using commercial kits and a gem premier 3000 ( instrumentation laboratory , usa ) . glycated hemoglobin a1c ( hba1c ) levels were measured using an hba1c meter from bio - rad laboratories , ltd . ( shanghai , china ) . the estimated glomerular filtration rate ( egfr ) was calculated by using the estimating equation from chinese patients with ckd . the results are expressed as the mean  sd for quantitative variables with normal distributions . pairwise comparisons of the four groups were performed using the tukey and kruskal - wallis nonparametric anova tests . a mann - whitney u analysis was used as the nonparametric test for the two subgroups . the risk markers for the diagnosis of dka and dk were assessed by multiple logistic regression analyses . receiver operating characteristic ( roc ) curve analyses were performed to determine the diagnostic performance of each variable . a total of 160 cases were included in this study . regarding age , gender , and diabetic type there were 15 patients with mild dka , 10 patients with moderate dka , and 15 patients with severe dka . the glycemic variables ( plasma glucose and hba1c levels ) had significantly higher values in the three diabetic patient groups than in the control group ( p < 0.001 ) . the glycemic variables had higher values in the dka and dk groups than in the non - dk group ( p < 0.05 ) . the difference in the duration of diabetes reached statistical significance ( p < 0.05 ) . the differences in the kidney - liver function values among the four groups were statistically significant ( p < 0.05 ) . this study demonstrated that most of the liver function - related concentrations were significantly lower in dka patients compared with the other three groups ( p < 0.001 or p < 0.05 ) . serum creatinine and uric acid levels were significantly elevated in the dka patients ( p < 0.05 ) . accordingly , the egfr levels were significantly elevated in the dka patients ( p < 0.05 ) . however , the levels of ast and bilirubin were not different among the four groups . of all of the liver function parameters in dk patients , the levels of ggt , total protein , albumin , globulin , and prealbumin were significantly lower than in patients with stable diabetes and control subjects ( p < 0.001 and p < 0.05 , resp . ) . as shown in table 2 , the dka patients were divided into t1d and t2d subgroups . plasma glucose levels at the time of admission were significantly higher in the patients with t1d compared with the patients with t2d ( 31.82  8.53 in addition , the patients with t2d were older than the patients with t1d ( 35  19 years versus 52  10 years , p = 0.001 ) . the levels of prealbumin were similar between the t1d and the t2d cases ( p = 0.775 ) . no significant differences were observed regarding the other parameters . as in table 3 , the dk and dka patients were divided into infection and noninfection subgroups , respectively . the infection subgroup contained more female cases and older individuals ( p < 0.05 ) . among dk patients , the infection subgroup had significantly lower levels of albumin and alt ( p = 0.016 and p = 0.001 , resp . ) . however , among dka patients , protein levels related to kidney - liver function were similar in both subgroups . furthermore , there was no difference in the prealbumin levels of the two subgroups . as shown in table 4 , there were 15 patients with severe dka , 10 patients with moderate dka , and 15 patients with mild dka . the levels of arterial ph , hco3 , and prealbumin were significantly lower in the severe dka patients compared with the mild / moderate dka patients ( p < 0.05 ) . for the rest of the variables , there were no significant differences between the mild / moderate and severe dka cases . when the dka and dk resolved after treatment , the levels of hco3 , arterial ph , and plasma glucose returned to normal . accordingly , the kidney function parameters declined to the normal range , but liver function - related levels were higher than at admission ( all p < 0.05 , table 1 ) . bivariate correlation analyses were performed to assess the relationships at baseline in dka and dk patients ( figure 1 ) . in dka patients , serum prealbumin levels r = 0.401 , p = 0.010 ) , hco3 levels ( figure 1(b ) : r = 0.350 , p = 0.027 ) , and arterial ph ( figure 1(c ) : r = 0.597 , p < 0.001 ) . in dk patients accordingly , ph was the most significant factor influencing the prealbumin levels (  = 0.768 , p < 0.001 ) but the levels of albumin (  = 0.292 , p = 0.024 ) and hco3 (  = 0.299 , p = 0.129 ) were not . multiple logistic regression analyses with significant clinical variables ( albumin and prealbumin levels ) were performed for the dka and dk groups . the odds ratios ( ors ) and 95% confidence intervals ( cis ) were calculated . the roc curve for the comparison of prealbumin levels in dka and dk patients is shown in figure 2 . accordingly , there were no significant differences in the prealbumin levels of dka and dk patients . to examine the predictive ability of prealbumin levels in estimating hyperglycemic crises , differences in the auc values between dka and dk the present study demonstrates that kidney - liver function is significantly altered in patients with dk and dka . to our knowledge the data in the current study showed that in patients with ketoacidosis , the values of glycemic and renal variables were significantly increased , but the levels of protein biomarkers and egfr were markedly reduced . although the exact mechanism behind this phenomenon is unclear , it can be concluded that the most significant factor influencing prealbumin levels might be metabolic acidosis status . it is observed that cytokine and inflammatory mediators were increased , but the physiological protein were markedly reduced in patients with ketoacidosis [ 4 , 5 , 17 , 19 , 20 ] . insulin administration had a favorable effect on glucose levels and protein synthesis in the liver . the diagnostic analysis presented here showed that lower prealbumin levels had a significant ability to reflect the presence of hyperglycemic emergencies . this study design limits the interpretation of the data because t1d and t2d have completely different pathophysiological mechanisms . however , kidney - liver function had a similar variation tendency in t1d and t2d subgroups . although our results can not replace traditional diagnostic criteria , this study adds complementary laboratory data by elucidating the patterns of kidney - liver function from stable condition to ketoacidosis . hyperketonemia with or without acidosis is considered to be an acute complication of poorly controlled or newly diagnosed diabetes mellitus . higher h levels may significantly reduce the liver 's production and release of enzymes and proteins . in the present study , total protein , albumin , globulin , and prealbumin levels were significantly lower in the severe ketoacidosis cases compared with the mild / moderate cases . elevated levels of ketone bodies can result in oxidative damage , accelerated apoptosis , and inhibition of cell growth in monocytes , which can lower the monocyte count . in contrast to the levels observed at admission , the kidney function parameters recovered to the normal range , whereas the levels of proteins related to liver function increased after insulin treatment . a mild increase in ast and alt levels is occasionally observed among patients with dk or dka after insulin treatment , although the exact mechanism is still undefined . it has been noted that dka is associated with severe insulin deficiency , active systemic inflammatory processes , and oxidative stress [ 4 , 19 , 20 ] . based on previous studies and our results , this clustered pathophysiological status may play a role in the development of kidney - liver function . mild infections can cause ketosis and ketoacidosis , although this was not the case in this study , indicating that the kidney and liver were not functioning well . the effect of dka on kidney - liver function was far greater than the effect resulting from a mild infection . the magnitude of specific deficits in an individual patient varies , depending on the duration and severity of t1d or dka [ 13 , 21 ] . the success of treatment is significantly associated with the correct management of hyperglycemia reduction , metabolic acidosis rectification , and electrolyte deficit replacement . alterations of blood flow and endothelial function precede development of complications in t1d . lowering blood glucose insulin therapy is the cornerstone of treatment for dka and dk , which can also result in an anti - inflammatory effect . biomarker discovery is known to be a valuable field of study and has become one of the most attractive subdisciplines in clinical proteomics for human diseases . prealbumin , a visceral protein , is sensitive to protein malnutrition , and this biomarker has been detected in urine . in the current study , prealbumin levels however , prealbumin levels can not be used to distinguish between infected and noninfected patients . therefore , we can conclude that ketoacidosis induces changes in acute - phase response protein . assessment of prealbumin levels will be helpful not only in early diagnosis but also in determining the prognosis of t2d patients . one limitation of this cross - sectional study is that the results represent preliminary evidence from a small study of patients with hyperglycemic emergencies . the clinical significance and the potential role of the alterations of prealbumin levels remain to be explored , particularly in diabetic patients with acute or chronic complications . in summary , dk and dka deteriorate liver and kidney function parameters , especially in patients with ketoacidosis . after considering the values of glycemic variables , the diagnosis of a hyperglycemic crisis should be cautious when based on lower prealbumin levels in overt hyperglycemia .
studies on the alterations of liver and kidney function parameters in patients with diabetic ketoacidosis ( dka ) and diabetic ketosis ( dk ) were limited . 
 participants with dka , dk , non - dk , and healthy controls were enrolled in the current study . 
 parameters of liver and kidney function were measured and evaluated . 
 the patients with dka had higher levels of plasma glucose , hemoglobin a1c ( hba1c ) , uric acid , and creatinine but lower levels of transferases and protein compared with the other three groups ( p < 0.05 for all ) . 
 the patients with dk had higher levels of plasma glucose and hba1c but lower levels of glutamyl transpeptidase and protein compared with the non - dk and control groups ( p < 0.05 ) . 
 prealbumin levels were significantly reduced in the severe dka patients compared with the mild / moderate dka patients . 
 serum prealbumin levels were correlated with albumin levels ( r = 0.401 , p = 0.010 ) , hco3 ( r = 0.350 , p = 0.027 ) , and arterial ph ( r = 0.597 , p < 0.001 ) in the dka patients . 
 a diagnostic analysis showed that lower prealbumin levels significantly reflected the presence of hyperglycemic emergencies ( p < 0.001 ) . 
 liver and kidney function parameters deteriorated , especially in dka . 
 prealbumin levels can be of value in detecting the presence of hyperglycemic crisis . 
 this clinical trial is registered with chictr - och-12003077 .