Loss of sex difference in high-density lipoprotein cholesterol in diabetic women during acute stress.

Abstract

The gender gap in high-density lipoprotein cholesterol (HDL-C) is well documented in health and also maintained in diverse chronic conditions, including menopause and diabetes. The mechanism for this difference in HDL-C and its regulation is not well understood. We evaluated whether this gender gap is maintained during acute stress. Diabetic patients with metabolic decompensation (n=179) were studied in the fasting state within 24 hours of admission to hospital, and again at outpatient follow-up. Fasting lipids and measures of glycemic control were evaluated on both occasions. The population was predominately minority, 78% Hispanic or African American. During admission, fasting lipid concentrations were not different in women (W) (n = 88) and men (M) (n = 91); serum total cholesterol (total-C), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and HDL-C were similar. Glycemic control was also similar; hemoglobin A1c (A1C) and serum glucose at presentation to hospital were not different in men and women. Compared with a subset of patients with pre-admission data (W, 35; M, 24), a decline of HDL-C was observed, greater in women (P = .005). At outpatient follow-up after admission, median duration approximately 4 months in each group (P = .39), changes in TG, LDL-C, and total-C from baseline admission were not different in men and women. In contrast, whereas HDL-C increased in both groups, the increase (median [interquartile range]) was significantly greater in women, 11 (4, 23) vs 6 (-1, 15) mg/dL (P < .003). This larger increase restored the gender gap in fasting HDL-C, 48 (39, 61) and 41 (36, 49) mg/dL in women and men at follow-up (P < .002). A1C improved similarly in each group. The sex difference in HDL-C levels is lost at time of admission to hospital in patients with diabetes, and returns when acute stress has resolved. These results raise the possibility that recurrent episodes of acute stress may lead to cumulative loss of the HDL-C advantage in women.