diabetes affects an estimated 285 million individuals worldwide , most of whom have type 2 diabetes mellitus ( t2 dm ) . this number is expected to increase , with asia becoming an epicenter of t2 dm thanks to urbanization and increasingly sedentary lifestyle . apart from chronic complications , individuals with inadequately controlled disease may experience hyperosmolar hyperglycemic syndrome ( hhs ) and , less frequently , diabetic ketoacidosis ( dka ) . in hhs , residual insulin reserve minimizes ketosis , whereas substantial insulin deficiency in dka results in ketone formation . dka involves a constellation of metabolic acidosis , ketosis , and dehydration with a mortality rate of nearly 10% . traditionally considered a unique feature of type 1 diabetes , dka is increasingly recognized in adults with t2 dm . recent epidemiologic survey revealed that one - third of individuals hospitalized for dka in fact harbored t2 dm , which represents a sizable population given the prevalence of hospitalizations related to ketoacidosis . considering the substantial mortality risk and complications associated with dka , identification of diabetic individuals at risk of ketosis and early preventive intervention will likely improve clinical outcome . although hemoglobin a1c ( hba1c ) is an established indicator of glycemic control , it has limited correlation with disease severity during hyperglycemic crisis . in contrast , several studies have validated serum albumin as a prognostic marker in severe illness . importantly , in the context of diabetes , albumin synthesis is dependent on adequate insulin reserve [ 810 ] . in an outpatient setting , serum albumin concentration was found to be inversely associated with hba1c , suggesting that hypoalbuminemia may reflect insulin deficiency and subsequent hyperglycemia . essentially , serum albumin may be an indirect yet sensitive indicator of insulin secretory reserve , which influences both ketosis risk and glycemic control . serum albumin concentration may have an advantage over conventional markers such as c - peptide , which is susceptible to interference by blood glucose level and may not closely reflect insulin secretion . on the basis of these considerations , this study investigated the association between serum albumin concentration and ketosis risk in hospitalized individuals with t2 dm . furthermore , the relationship between serum albumin concentration and long - term glycemic control , as represented by hba1c level , was examined . this was a retrospective cross - sectional study conducted at a medical center in taiwan . individuals hospitalized between september 2010 and august 2015 in the endocrinology ward with a principal diagnosis of hyperglycemia were screened for eligibility . inclusion criteria were individuals exceeding 21 years of age , with a preexisting diagnosis of t2 dm , and blood glucose concentration above 13.9 millimoles per liter ( mmol / l ) at admission . the diagnosis of diabetes was made using american diabetes association criteria , with fasting plasma glucose  126 milligrams per deciliter ( mg / dl ) , 2-hour post - prandial plasma glucose  200  mg / dl , or hba1c exclusion criteria encompassed individuals without measurement of serum albumin concentration , urine ketone , or hba1c . patients with active infection , myocardial infarction , or cerebrovascular event that may adversely affect glycemic control were also excluded . furthermore , individuals with liver cirrhosis , malignancy , or overt proteinuria that may alter albumin production or excretion were ineligible . laboratory data during hospitalization were analyzed , while hba1c closest to admission within the previous three months was selected . hypoalbuminemia was defined as serum albumin concentration below 3.0 grams per deciliter ( g / dl ) . furthermore , substantial ketonemia was defined as serum beta - hydroxybutyrate ( bhb ) concentration exceeding 3  mmol / l , which has been established as one of the criteria for dka . hba1c was measured by ion - exchange high - performance liquid chromatography using biorad variant ii turbo system . serum albumin was measured by bromocresol purple method using beckman coulter unicel dxc 800 synchron clinical systems . student 's t - test was used to compare continuous variables and pearson 's chi - squared test for categorical variables . cross - tabulation enabled calculation of the odds ratio ( or ) and 95% confidence interval ( ci ) . all calculations were based on a two - sided hypothesis with p < 0.05 interpreted as significant . statistical package for the social sciences version 22 after screening according to the abovementioned criteria , 255 individuals were included in the study . individuals with serum albumin concentration above 3.0  g / dl were designated as normoalbuminemic controls , while those with serum albumin below this threshold were classified as hypoalbuminemic cases . both groups were similar in age , sex , body mass index , and serum creatinine concentration . the prevalence of ketonuria was 48% in hypoalbuminemic subjects compared to 30% in those with normoalbuminemia ( or : 2.15 ; 95% ci : 1.263.57 ; p = 0.004 ) . moreover , for the 156 subjects with serum bhb measurement in addition to urine ketones , 33% of individuals with hypoalbuminemia harbored ketonemia exceeding 3  mmol / l , compared to 19% of those with normoalbuminemia ( or : 2.12 , 95% ci : 0.994.48 , p = 0.051 ) . pearson 's correlation was employed to uncover the relationship between serum albumin concentration and other clinical variables , and the results are documented in table 3 . serum albumin concentration was found to be negatively correlated with hba1c ( r = 0.293 , p < 0.001 ) . a plot of mean hba1c to serum albumin concentration in tertiles also revealed an inverse relationship , as demonstrated in figure 1 . this has been corroborated by impaired liver production of albumin during insulin deficiency and a 10% increase in daily albumin synthesis after insulin infusion in diabetic individuals . in animal models of insulin deficiency , serum albumin concentration was normalized after three days of insulin therapy , further strengthening the link between insulin reserve and serum albumin concentration . in clinical practice , an association between hypoalbuminemia and insulin deficiency may explain the increased mortality rate in hyperglycemic individuals with low serum albumin concentration . in this study , diabetic individuals with low serum albumin concentration were susceptible to ketosis , as evidenced by a higher prevalence of ketonuria and a trend towards increased ketonemia in this population . therefore , hypoalbuminemia may be a useful marker of ketosis risk , which in turn suggests underlying insulin deficiency . in this context , serum albumin concentration may indirectly reflect a diabetic individual 's insulin reserve and thus serve as an indirect indicator of glycemic control . one advantage of utilizing serum albumin as a measure of glycemic control is its shorter half - life of 21 days , which renders its serum concentration more sensitive to recent change in average blood glucose level than hba1c . there is no convenient measurement of beta cell function , with several investigators using proinsulin to insulin ratio for research purposes . however , proinsulin measurement is unavailable to most hospital laboratories , and the proinsulin to insulin ratio will likely be altered by exogenous insulin used to treat hyperglycemia . furthermore , current guidelines for hyperglycemic crisis target the resolution of hyperglycemia and metabolic acidosis . in practice , numerous recuperated patients experience recurrent ketosis after withdrawing insulin therapy , implying that impaired insulin secretion persists after clinical recovery . serum albumin , which is commonly available to hospital laboratories and indicative of an individual 's insulin secretory reserve , may assist clinicians in determining the duration of insulin therapy . first , diabetic inpatients with hypoalbuminemia are very likely to have depleted insulin reserve and are likely to require early initiation of insulin therapy to prevent ketosis . furthermore , serum albumin concentration may enable stratification of hyperglycemic individuals with respect to ketosis risk and prognosis . in fact , serum albumin has been validated as a measure of disease severity in the acute physiology and chronic health evaluation scoring system . finally , along with hba1c , serum albumin may serve as an adjunctive measure of glycemic control which better reflects recent change in average blood glucose level . this study benefits from a population of individuals who were hospitalized principally for acute hyperglycemia , with the exclusion of factors such as active infection , liver cirrhosis , malignancy , and overt proteinuria that may adversely affect glycemic control . to enable accurate interpretation of the results , only laboratory data during the hospitalization period were analyzed , with the exception of hba1c , for which measurements within the three months prior to admission were selected . finally , demographic characteristics were similar between cases and controls , which minimized potential confounding effects . because serum albumin concentration was more frequently tested in malnourished or severely ill individuals who were suspected of hypoalbuminemia , this may have led to an inherent selection bias . furthermore , treatment modalities prior to hospitalization that affect ketosis risk and glycemic control , such as exogenous insulin , were not taken into account . finally , although serum bhb is a more specific marker of ketosis , it was only available for a subset of individuals in this study . in conclusion , serum albumin concentration is inversely associated with ketosis risk in hospitalized individuals with t2 dm . diabetic individuals with low serum albumin concentration are at risk of ketosis and may require early initiation of insulin therapy to prevent complications . serum albumin concentration potentially mirrors an individual 's insulin secretory reserve , which subsequently influences glycemic control and ketosis risk . serum albumin concentration is a promising prognostic marker in hospitalized diabetic individuals with acute hyperglycemia .
objective . 
 this study examined the association between serum albumin concentration and ketosis risk in hospitalized individuals with type 2 diabetes mellitus ( t2 dm ) . methods . 
 a retrospective cross - sectional study was conducted at a medical center in taiwan . 
 inclusion criteria were endocrinology ward inpatients exceeding 21 years of age , with preexisting diagnosis of t2 dm , and blood glucose above 13.9 millimoles per liter ( mmol / l ) at admission . 
 individuals without measurement of serum albumin , urine ketone , or hemoglobin a1c , or harboring active infection , myocardial infarction , cerebrovascular event , cirrhosis , malignancy , or overt proteinuria were excluded . using serum albumin concentration below 3.0 grams per deciliter to define hypoalbuminemia , 
 151 hypoalbuminemic cases and 104 normoalbuminemic controls were enrolled . 
 the presence of ketones in urine established ketosis . 
 results . 
 the prevalence of ketonuria was 48% in hypoalbuminemic subjects compared to 30% in normoalbuminemic controls ( odds ratio ( or ) : 2.15 ; 95% confidence interval ( ci ) : 1.263.57 ; p = 0.004 ) . 
 moreover , among the 156 subjects with serum beta - hydroxybutyrate measurement in addition to urine ketone , 33% of the hypoalbuminemic individuals had ketonemia exceeding 3  mmol / l compared to 19% of those with normoalbuminemia ( or : 2.12 , 95% ci : 0.994.48 , p = 0.051 ) . conclusions . 
 serum albumin concentration is inversely associated with ketosis risk in hospitalized individuals with t2 dm .