Introduction:Non-alcoholic fatty liver disease (NAFLD) is associated with Type 2 diabetes (T2DM) and the metabolic syndrome, and can progress to chronic liver disease. We examined the incidence of elevated (>35 iu/l) alanine transaminase (ALT), as a surrogate marker for NAFLD, in patients with newly diagnosed T2DM.Materials and Methods:Retrospective analysis of ALT with metabolic parameters, in 606 consecutive patients presenting to district wide education sessions for newly diagnosed T2DM.Results:ALT was elevated in 155 patients (25.6% (95% CI 22.1, 29.2)), who tended to be older (mean difference 7.3 years (5.2, 9.5), P < 0.001), heavier (body mass index (BMI) mean difference 2.0 kg/m2 (1.0, 3.0), P < 0.001), and more likely to be male (M:F raised ALT 104:51, normal ALT 219:232, P < 0.001), with higher triglycerides (median difference 0.2 mmol/l, P = 0.001) and lower HDL cholesterol (mean difference 0.09 mmol/l (0.02, 0.15), P = 0.001). There were no statistically significant differences in HBA1C or total cholesterol.Conclusions:In a well-defined population of newly diagnosed people with T2DM, there is a high incidence of abnormal ALT levels, which is associated with features of the metabolic syndrome (obesity and lipid abnormalities), but not glycemic control.

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...

The oestrogen-associated advantage in clearance of dietary lipid we observed in non-diabetic post-menopausal women is not seen in post-menopausal diabetic women. This is likely to promote an atherogenic lipoprotein profile and may contribute to the loss of CVD protection seen in diabetic women.