Background Plasma levels of liver transaminases, including alanine aminotransferase (ALT), are elevated in most cases of nonalcoholic fatty liver disease (NAFLD). Elevated ALT levels are associated ...with insulin resistance, and subjects with NAFLD have features of the metabolic syndrome that confer high‐risk cardiovascular disease. Alanine aminotransferase predicts the development of type 2 diabetes (DM2) in subjects with the metabolic syndrome. However, the role of elevated ALT levels in subjects with overt DM2 has yet not been explored.
Materials and methods In a cross‐sectional study, 64 normotriglyceridaemic subjects with DM2 were studied with regard to the relation between liver transaminases with whole‐body insulin sensitivity, measured with the euglycaemic hyperinsulinaemic clamp and with brachial artery flow‐mediated dilation (FMD) as a marker of endothelial dysfunction.
Results On average, patients were normotriglyceridaemic (plasma triglycerides 1·3 ± 0·4 mmol L−1) and had good glycaemic control (HbA1c 6·2 ± 0·8%). The mean ALT level was 15·0 ± 7·5 U L−1, and the mean aspartate aminotransferase concentration equalled 10·6 ± 2·6 U L−1. Alanine aminotransferase levels were negatively associated with whole‐body insulin sensitivity as well as with FMD (both P = 0·03, in multivariate analyses; regression coefficients beta 95%CI: −0·76 −1·4 to −0·08 and −0·31 −0·58 to −0·03 respectively).
Conclusions In metabolically well‐controlled patients with DM2, ALT levels are related to decreased insulin‐sensitivity and an impaired conduit vessel vascular function.
To assess the expected precision of HbA1c measurements and the magnitude of HbA1c changes eliciting the advice to change treatment among diabetes care professionals.
A seven-item questionnaire was ...sent to participants through a website. The survey focused on physicians and nurses involved in diabetes care.
In total, 104 physicians, 177 diabetes specialist nurses, and 248 primary care nurses responded to the survey. A large number of the nurses (44%) and only a small number of the physicians (4%) were not aware of the inherent uncertainty of HbA1c results. Nurses considered adjusting therapy based on very small changes in HbA1c whereas physicians in general adhere to 0.5% (5.5 mmol÷mol) as a clinically meaningful cut-off point. After therapy adjustment, a very small (0.1%) or no increase in HbA1c was considered to be significant enough to conclude that glucose regulation has worsened by 49% of the nurses and only 13% of the physicians.
Significant differences exist in the interpretation of changes in HbA1c results between physicians and nurses. Nurses consider therapy changes based on very small changes in HbA1c, whereas physicians preferably agree to the clinically relevant change of 0.5% (5.5 mmol÷mol). Changing therapy based on relatively small changes in HbA1c might lead to undue adjustments in the treatment of patients with diabetes. There is a clear need for more training for all diabetes care professionals about both the clinical significance and accuracy of HbA1c measurements.
Aims To study the association between alanine aminotransferase (ALT) and the 6‐year risk of the metabolic syndrome in a population‐based study in Caucasian men and women.
Methods The association of ...ALT with the 6‐year risk of the metabolic syndrome in 1097 subjects, aged 50–75 years, was assessed in the Hoorn Study with logistic regression analysis. Subjects with the metabolic syndrome at baseline, defined according to the Adult Treatment Panel III of the National Cholesterol Education Program, were excluded.
Results After 6.4 (range 4.4–8.1) years follow‐up, 226 subjects (20.6%) had developed the metabolic syndrome. The odds ratio (95% confidence interval) for developing the metabolic syndrome, adjusted for age, sex, alcohol intake and follow‐up duration was 2.25 (1.50–3.37) for subjects in the upper tertile compared with those in the lower tertile of ALT. This association persisted after additional adjustment for all the baseline metabolic syndrome features 1.62 (1.02–2.58). Among the individual components of the metabolic syndrome, ALT was significantly associated only with fasting plasma glucose at follow‐up.
Conclusions These data suggest that ALT is associated with risk of the metabolic syndrome in a general population of middle‐aged Caucasian men and women, further strengthening the role of ALT as an indicator for future metabolic derangement. These findings warrant further studies to elucidate the role of non‐adipose tissue fat accumulation in the pathogenesis of complications related to the metabolic syndrome.
Diabet. Med. 24, 430 – 435 (2007)
Postprandial hyperlipidemia, which is exaggerated and prolonged in insulin-resistant individuals, has been associated with cardiovascular disease. The objective of this study was to investigate ...whether and how the composition, size and function of high-density lipoprotein (HDL) and low-density lipoprotein (LDL) particles are affected in the postprandial state among males with the metabolic syndrome (MetS) or type 2 diabetes (T2DM), compared with controls.
A total of 14 males with T2DM, 14 with the MetS and 14 age-matched controls were given three standardized high-fat mixed meals (900 kcal; 50-g fat, 75-g carbohydrate and 35-g protein) as breakfast, lunch and dinner. Blood sampling was performed just before each meal, and 4 and 8 h after the last meal. HDL and LDL were isolated by ultracentrifugation and analyzed for their composition, particle diameter and functional properties.
Postprandial triglycerides levels in plasma, HDL and LDL particles increased significantly in all groups (P<0.01). Compared with the control subjects, patients with T2DM had smaller LDL particles, and in agreement, a lower cholesterol-to-protein content in both fasting and postprandial samples. A prolonged increase in susceptibility of LDL to oxidation was found in all subjects, but was most evident in T2DM. The postprandial effect on LDL oxidation was associated with an increase in LDL triglyceride (r=0.29, P<0.05). In T2DM the anti-oxidative capacity of HDL trended to impairment after the third meal.
Postprandial increases in triglycerides, especially in T2DM, are accompanied by pro-atherosclerotic functional changes in HDL and LDL particles.
Abstract The present study aimed to compare the associations of postprandial glucose (ppGL) and postprandial triglycerides (ppTG) with carotid intima media thickness (cIMT) in women with normal ...glucose metabolism (NGM) and type 2 diabetes (DM2). Post-menopausal women (76 with NGM, 78 with DM2), received two consecutive fat-rich and two consecutive carbohydrate-rich meals on separate occasions. Blood samples were taken before and 1, 2, 4, 6 and 8 h following breakfast; lunch was given at t = 4. Ultrasound imaging of the carotid artery was performed to measure cIMT. In women with NGM, an increase of 1.0 mmol/l glucose following the fat-rich meals was associated with a 50 μm cIMT increase ( p = 0.04), and following the carbohydrate meals, an increase of 1.8 mmol/l glucose was associated with a 50 μm larger cIMT ( p = 0.08). These associations were not explained by classical cardiovascular risk factors. However, no association between ppGL and cIMT was found in women with DM2 and ppTG were not associated with cIMT. The association between ppGL and cIMT in normoglycaemic women suggests that ppGL in the normal range is a marker or a risk factor for atherosclerosis. Postprandial glucose levels might be a better indicator of risk than post-OGTT glucose levels or triglyceride levels.
Background/Objective: Early insulin secretion following a meal is representative for normal physiology and may depend on meal composition. To compare the effects of a fat-rich and a carbohydrate-rich ...mixed meal on insulinogenic index as a measure of early insulin secretion in normoglycemic women (NGM) and in women with type 2 diabetes mellitus (DM2), and to assess the relationship of anthropometric and metabolic factors with insulinogenic index. Subjects/Methods: Postmenopausal women, 76 with NGM and 64 with DM2, received a fat-rich meal and a carbohydrate-rich meal on separate occasions. Early insulin response was estimated as insulinogenic index (delta insulin(0-30 min)/delta glucose(0-30 min)) for each meal. Associations of fasting and postprandial triglycerides, body mass index, waist and hip circumference and alanine aminotransferase with insulinogenic indices were determined. Results: Women with NGM present with higher insulinogenic index than women with DM2. The insulinogenic index following the fat-rich meal (delta I(30)/delta G(30) (fat)) was higher than the index following the carbohydrate-rich meal (delta I(30)/delta G(30) (CH)) (P<0.05 in women with DM2, and not significant in women with NGM). In women with DM2, homeostasis model assessment for insulin resistance was positively associated with delta I(30)/delta G(30) (CH). In women with NGM, waist circumference was independently and inversely associated with delta I(30)/delta G(30) (fat) and with delta I(30)/delta G(30) (CH); hip circumference was positively associated with delta I(30)/delta G(30) (fat). Conclusions: The insulinogenic index following the fat-rich meal was higher than following the isocaloric carbohydrate-rich meal, which might favorably affect postprandial glucose excursions, especially in women with DM2. The association between a larger waist circumference and a lower meal-induced insulinogenic index in women with NGM requires further mechanistic studies.
Statins are thought to have anti-atherogenic effects beyond cholesterol lowering. One such mechanism may involve reduction of oxidative stress. The aim of our study was to investigate and to compare ...the oxidative stress lowering capacity of atorvastatin with that of simvastatin in patients at high risk for cardiovascular disease using conventional markers and sensitive markers measured by highly specific techniques such as liquid chromatography tandem mass spectrometry.
We included 30 statin-naive patients with diabetes mellitus, and/or obesity, and/or hypertension (12 male, 18 female, mean age 44.8±11.1 years), and randomised them to receive either atorvastatin 10 mg or simvastatin 40 mg daily to obtain an equimolar cholesterol reduction. Blood and urine samples were obtained at baseline and at 1, 6 and 12 weeks.
Low-density lipoprotein (LDL) cholesterol and coenzyme Q10 decreased significantly in both groups. Simvastatin caused a faster initial LDL cholesterol lowering than atorvastatin (p=0.01), but the overall effect after 12 weeks of atorvastatin and simvastatin was similar. Plasma myeloperoxidase and malondialdehyde did not change during the study period in the two groups. Urinary F2-isoprostanes decreased gradually and significantly in the atorvastatin group but not in the simvastatin group, but the between-group difference was not significant. Urinary 8-hydroxy-2-deoxyguanosine did not change in the two groups.
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