Premenopausal Advantages in Postprandial Lipid Metabolism Are Lost in Women With Type 2 Diabetes

Abstract

OBJECTIVE -Women with type 2 diabetes appear to lose the protection against cardiovascular disease afforded by estrogens. We examined the effects of menopausal status on postprandial clearance of dietary fat in healthy and diabetic women.RESEARCH DESIGN AND METHODS -Fasting subjects (premenopausal and postmenopausal control subjects, premenopausal and postmenopausal diabetic women, all n ϭ 8) were given a meal containing the stable isotope 1,1,1-13 C-tripalmitin, with blood and breath sampled for 6 and 24 h, respectively, in the postprandial period. Lower levels of 13 C-palmitic acid ( 13 C-PA) in the triglyceride fraction implies more efficient chylomicron clearance, lower levels of 13 C-PA in the nonesterified fatty acid (NEFA) fraction implies improved dietary NEFA entrapment, and higher levels of 13 CO 2 in the breath denote more efficient of oxidation of dietary-derived lipid.RESULTS -In diabetic women, there were no differences between the pre-and postmenopausal groups for any of these parameters. In contrast, premenopausal control subjects, compared with postmenopausal control subjects, had lower CONCLUSIONS -The premenopausal advantage in clearance of dietary lipid is not seen in premenopausal diabetic women. This is likely to promote an atherogenic lipoprotein profile and may contribute to the loss of cardiovascular disease protection seen in diabetic women. Diabetes Care 26:3243-3249, 2003P atients with type 2 diabetes have an increased cardiovascular risk, which is particularly marked in diabetic women (1). In the nondiabetic population, women are relatively protected against coronary heart disease (CHD) when compared with men, an effect attributed to the physiological effects of estrogens (2,3). In contrast, diabetic women have an equivalent rate of CHD to diabetic men, appearing to lose the protection of estrogens (1).There are many contender mechanisms to account for the high CHD risk observed in diabetes (4), including diabetic dyslipidemia, which is thought to be particularly atherogenic and is characterized by fasting hypertriglyceridemia, low HDL cholesterol, and small dense LDL (4). The impact of the postprandial triglyceride load will be underestimated by examining fasting triglyceride values, as the typical western diet and pattern of feeding usually results in maintenance of the postprandial state for ϳ16 h each day (5). Postprandial triglyceride levels are determined by the metabolism of chylomicrons and VLDL. Chylomicrontriglyceride is hydrolyzed by the action of the enzyme lipoprotein lipase (LPL) releasing nonesterified fatty acids (NEFAs), the remaining chylomicron remnants being taken up by the liver via LDL receptors (6). Premenopausal nondiabetic women have been shown to have lower postprandial triglyceride levels than postmenopausal women (7,8), probably due to upregulation of hepatic LDL receptor by estrogens (9), thus increasing chylomicron remnant clearance. However, reduced chylomicron clearance is a feature of diabetes (10).We hypothesized that impaired clearance of circulatin...

Rapid onset of cardiomyopathy in STZ-induced female diabetic mice involves the downregulation of pro-survival Pim-1

“…In fact, while non-diabetic women are relatively protected from cardiovascular disease, this advantage is lost in diabetes [6]. In the Framingham study, the reported incidence of symptomatic HF was 2.4-fold higher in men and 5.0-fold higher in women with diabetes compared to their non-diabetic peers, [7] a finding confirmed by several other studies [8-10].…”

Percentage of body fat and plasma glucose predict plasma sialic acid concentration in type 2 diabetes mellitus

“…People with type 2 diabetes mellitus were recruited from a hospital clinic (controlled by diet or oral hypoglycemics), whereas controls were recruited from the community via advertising. All women were postmenopausal (some of these volunteers were a subgroup of the postmenopausal female volunteers described by Masding et al [19]). Postmenopausal status was verified by amenorrhea for more than 1 year and elevated gonadotrophins.…”

“…Serum triglycerides, insulin, and glucose were measured using standardized laboratory techniques as described in reference [19]. Plasma sialic acid was quantified using an enzymatic method (Boehringer Mannheim, Lewes, Sussex, UK) on a Roche Cobas Fara analyzer (Roche, Basel, Switzerland) [20].…”

Therapeutic potential of antisense oligonucleotides for the management of dyslipidemia

“…Studies assessing dietary fatty acid oxidation using 13 C-labeled fatty acids have shown that meal fatty acid oxidation tends to increase with body fat mass [89], in abdominally obese versus control men [90] and is increased in postmenopausal women with T2D [91]. It should be noted that rates of dietary fatty acid oxidation were likely underestimated in the latter studies because correction for the acetate retention factor was not applied.…”