a cross - sectional study of 1,819 consecutive patients with type 2 diabetes and serum triglycerides < 400 mg / dl was conducted at diabetes centers in three italian cities ( san giovanni rotondo [ sgr ] , catanzaro [ cz ] , and rome ) with institutional review board approval . age , sex , height and weight , medical history , smoking status ( current smokers vs. nonsmokers ) , and current medications  lipid - lowering agents in particular  were recorded for all patients . venous blood samples were collected after a fast of 8 h and analyzed to determine serum levels of a1c ( high - performance liquid chromatography , normal range 36% ) , glucose ( glucose - oxidase method ) , cholesterol ( total and hdl ) , and triglycerides ( standard enzymatic assays ) . ldl cholesterol was calculated with the friedewald formula : ldl cholesterol = total cholesterol  ( hdl cholesterol + [ triglycerides/5 ] ) . low hdl cholesterol was defined as levels of < 40 mg / dl ( men ) or < 50 mg / dl ( women ) ( 10 ) . multivariate logistic regression analysis was used to assess the effect of metabolic control on the presence / absence of low hdl cholesterol . after exclusion of intersample heterogeneity , the three data sets were pooled and analyzed together following adjustments for sample . analyses were performed with spss software , version 15 ( spss , chicago , il ) , and a p value of < 0.05 was considered significant . multivariate logistic regression analysis was used to assess the effect of metabolic control on the presence / absence of low hdl cholesterol . after exclusion of intersample heterogeneity , the three data sets were pooled and analyzed together following adjustments for sample . analyses were performed with spss software , version 15 ( spss , chicago , il ) , and a p value of < 0.05 was considered significant . higher a1c levels were recorded in sgr and cz ( p < 0.001 vs. rome ) . the prevalence of low hdl cholesterol ranged from 28% in rome to 34% in cz and 55% in sgr . in sgr , patients were more frequently treated with insulin than with oral hypoglycemic agents compared with the patients in rome and cz ; moreover , a smaller percentage of patients in sgr and cz were treated with hypolipemic therapy than in rome . at all three centers , a1c levels tended to be higher in patients with low hdl cholesterol than in those with hdl cholesterol levels 40/50 mg / dl . this difference was statistically significant in sgr ( 8.7 vs. 8.3% , p = 0.0001 ) and rome ( 7.0 vs. 6.7% , p = 0.04 ) but not in cz ( 7.8 vs. 7.5% , p = 0.2 ) . there was no significant interaction between the variables a1c level and sample in modulation of the risk of low hdl cholesterol ( p = 0.86 ) . clinical characteristics of the study populations data are expressed as mean  sd or percentage . analysis of pooled data revealed that a 1% increase in a1c values significantly increased the risk for low hdl cholesterol ( or 1.17 [ 95% ci 1.11.2 ] , p = 0.00072 ) . this effect did not change at all when age , sex , smoking status , and lipid - lowering therapy were added to the model ( 1.17 [ 1.11.2 ] , p = 0.00044 ) . the strength of this association was also maintained when additional adjustments for obesity ( bmi 30 kg / m ) and hypertriglyceridemia ( 150 mg / dl ) were included in the multivariate analysis 1.12 [ 1.051.18 ] , p = 0.00017 ) . the linear regression from individual data between a1c and hdl cholesterol is shown in the online appendix available at http://care.diabetesjournals.org/cgi/content/full/dc09-0256/dc1 . ldl cholesterol lowering therapy with statins reduces cvd in patients with type 2 diabetes and is recommended by current guidelines as the first - line approach for the treatment of diabetic dyslipidemia ( 11 ) . elevation of cardiovascular risk related to low hdl cholesterol , which is an independent predictor of major cardiovascular events ( 12 ) . consequently , increasing hdl cholesterol levels is now being proposed as an additional worthwhile therapeutic goal in diabetes ( 11 ) . because nearly half of all type 2 diabetic patients have low hdl cholesterol levels ( 5 ) , the variables associated with this phenomenon need to be clearly defined . in the large italian diabetic population we studied , ( 13 ) demonstrated a negative correlation between hdl cholesterol and serum glucose levels in diabetic subjects . more interesting , our study found the association between poor glycemic control and low hdl cholesterol remained significant even after adjustments for obesity and hypertriglyceridemia . both are highly prevalent in patients with type 2 diabetes , especially in those with poor glycemic control , and are known to independently lower hdl cholesterol . experimental findings demonstrated that glycation of hdl cholesterol impairs its functional ability to bind to the receptor and to promote intracellular cholesterol efflux ( 14 ) . it has also been observed that poor glycemic control promotes glycation of the protein component of hdl cholesterol ( apolipoprotein a1 ) , altering hdl cholesterol metabolism and its ability to activate lecithin - cholesterol acyltransferase and the reverse cholesterol transport pathway ( 15 ) . this is a mechanism by which glycated hdl cholesterol could worsen diabetic atherosclerosis . to our knowledge , these findings are the first evidence that impaired glycemic control is an important independent risk factor for low hdl cholesterol in patients with type 2 diabetes . if confirmed in future studies , this observation may provide an additional means for establishing optimal glycemic targets tailored to individual patient characteristics .
objectiveto determine whether the association observed between poor glycemic control and low hdl cholesterol in type 2 diabetes is dependent on obesity and/or hypertriglyceridemia.research design and methodswe performed a cross - sectional study of 1,819 patients with type 2 diabetes and triglycerides < 400 mg / dl enrolled at three diabetes centers in italy . 
 the risk for low hdl cholesterol was analyzed as a function of a1c levels . 
 odds ratios ( ors ) were calculated after adjustment for confounding factors.resultsa 1% increase in a1c significantly increased the risk for low hdl cholesterol ( or 1.17 [ 95% ci 1.11.2 ] , p = 0.00072 ) ; no changes were observed when age , sex , smoking , and lipid - lowering therapy were included in the model ( 1.17 [ 1.11.2 ] , p = 0.00044 ) . 
 the association remained strong after adjustments for obesity and hypertriglyceridemia in multivariate analysis ( 1.12 [ 1.051.18 ] , p = 0.00017).conclusionspoor glycemic control appears to be an independent risk factor for low hdl cholesterol in type 2 diabetes .