What is the effect of rosiglitazone treatment on insulin secretory function in insulin-resistant individuals? It depends on how you measure it

The goal of this study was to compare methods used to quantify the effect of rosiglitazone (RSG) on insulin secretory function, particularly estimates based on changes in fasting plasma glucose and insulin concentration vs daylong insulin responses to meals. To do this, we compared these measures of insulin secretion before and 3 months after RSG treatment in insulin-resistant individuals, subdivided into nondiabetic subjects (n = 29) and patients with type 2 diabetes mellitus (2DM) (n = 22). Insulin resistance was quantified by determining the steady-state plasma glucose concentration during the insulin suppression test and insulin secretory function by homeostasis model assessment of β-cell function (HOMA-β) and the total integrated daylong plasma insulin responses to mixed meals (insulin area under the curve). Baseline fasting and daylong plasma glucose concentrations were higher (P < .001) in patients with 2DM, associated with lower HOMA-β values (P < .001). However, neither fasting nor daylong insulin concentrations after mixed meals differed in the 2 groups. Insulin sensitivity improved (P < .001) after RSG administration, with decreases of 31% ± 23% and 21% ± 14% in steady-state plasma glucose concentration in nondiabetic and diabetic subjects, respectively. Although fasting and daylong plasma glucose and insulin concentrations fell (P < .001) in both groups of RSG-treated individuals, HOMA-β decreased in nondiabetic subjects and did not change in those with 2DM. In conclusion, RSG administration improved insulin sensitivity in both groups, associated with lower fasting and daylong glucose concentrations. Fasting and daylong insulin concentrations were also lower in both groups of RSG-treated subjects, but the values of HOMA-β indicated either a decrease (nondiabetics) or no change (diabetics) in insulin secretory function. These results suggest that measurements of HOMA-β may not provide a complete view of insulin secretory function, either when comparing diabetic with nondiabetic individuals or when assessing the response to RSG treatment in insulin-resistant individuals.     

Relationship between changes in insulin sensitivity and associated cardiovascular disease risk factors in thiazolidinedione-treated, insulin-resistant, nondiabetic individuals: pioglitazone versus rosiglitazone

This study compared the effects of administering rosiglitazone (RSG) vs pioglitazone (PIO) on cardiovascular disease risk factors in insulin-resistant, nondiabetic individuals with no apparent disease. Twenty-two nondiabetic, apparently healthy individuals, classified as being insulin resistant on the basis of a steady-state plasma glucose concentration of at least 10 mmol/L during the insulin suppression test, were treated with either RSG or PIO for 3 months. Measurements were made before and after drug treatment of weight; blood pressure; fasting and daylong glucose, insulin, and free fatty acid (FFA) levels; and lipid and lipoprotein concentrations. Insulin sensitivity (steady-state plasma glucose concentration) significantly improved in both treatment groups, associated with significant decreases in daylong plasma concentrations of glucose, insulin, and FFA. Diastolic blood pressure fell somewhat in both groups, and this change reached significance in those receiving PIO. Improvement in lipid metabolism was confined to the PIO-treated group, signified by a significant decrease in plasma triglyceride concentration, whereas triglyceride concentration did not decline in the RSG-treated group, and these individuals also had increases in total (P = .047) and low-density lipoprotein cholesterol (P = .07). In conclusion, RSG and PIO appear to have comparable abilities to improve insulin sensitivity and lower daylong glucose, insulin, and FFA concentrations in nondiabetic, insulin-resistant individuals. However, despite these similarities, their effects on lipoprotein metabolism seem to be quite different, with beneficial effects confined to PIO-treated individuals.     

Augmentation of nitric oxide is crucial for the time-dependent effects of rosiglitazone on blood pressure and baroreflex function in rats

OBJECTIVES: To determine the time-dependent effects of rosiglitazone (RSG) on blood pressure (MAP) and baroreflex sensitivity (BRS) and the involvement of nitric oxide (NO) in these effects. METHODS: Male Sprague-Dawley rats were treated with RSG (8 mg/kg per day, orally) or saline for 4, 8 and 12 weeks. BRS was determined by linear regression method with bolus injections of phenylephrine (PE-BRS) or sodium nitroprusside (NP-BRS). Insulin sensitivity (M value) was determined by euglycemic hyperinsulinemic clamp study. Vascular and cardiac responsiveness to isoproterenol, acetylcholine and NP were determined after ganglionic blockade. Effects of endogenous NO were examined by Nomega-nitro-L-arginine-methyl ester (L-NAME) administration. RESULTS: RSG treatment time-dependently decreased circulating lipids, insulin, glucose levels and insulin resistance (HOMA-IR) but increased plasma NOx levels. M values were progressively decreased in control rats, but remained unchanged in RSG-treated rats. Chronic RSG treatment progressively lowered MAP but reciprocally increased heart rate (HR). In addition, chronic RSG treatment significantly attenuated HR changes to methylatropine but enhanced HR changes to propranolol. Twelve-week RSG treatment enhanced PE-BRS which was suppressed by methylatropine but not propranolol, and attenuated NP-BRS which was sustained after methylatropine or propranolol. Moreover, 12-week RSG treatment also diminished cardiac responsiveness to isoproterenol and augmented vascular responsiveness to acetylcholine, but not to NP. L-NAME eliminated the differences in MAP and HR between groups, and reversed both RSG-induced enhanced PE-BRS and attenuated NP-BRS. Plasma NOx levels were highly correlated with RSG-mediated changes in the baseline MAP, HR and BRS. CONCLUSION: These data suggest that RSG-induced NO production is important for the time-dependent effects of RSG on MAP and BRS in rats.     

Pioglitazone decreases postprandial accumulation of remnant lipoproteins in insulin-resistant smokers

Background:  Fasting hypertriglyceridaemia has been reported to occur commonly in cigarette smokers and is thought to increase cardiovascular disease (CVD) risk in these individuals. More recently, it has been suggested that an increase in non-fasting triglycerides, rather than fasting hypertriglyceridaemia, is an independent CVD risk factor.
Methods:  In this study, we divided 24 smokers into insulin-resistant (IR) and insulin-sensitive (IS) groups by determining their steady-state plasma glucose concentrations during the insulin suppression test and compared fasting and daylong postprandial accumulation of total triglycerides and remnant lipoprotein (RLP) concentrations, before and after 3 months of pioglitazone (PIO) administration.
Results:  The two groups were similar in age, body mass index, race and gender distribution, but differed dramatically in insulin sensitivity. Baseline fasting and postprandial triglyceride, RLP cholesterol and RLP triglyceride concentrations were significantly higher in the IR smokers (p = 0.01 to <0.01). Insulin sensitivity and both fasting and postprandial triglyceride and RLP triglyceride levels decreased significantly (p = 0.05 to <0.01) in PIO-treated IR smokers, without any significant increase in weight. In contrast, there were no significant changes in either insulin sensitivity or fasting and postprandial triglyceride, RLP cholesterol and RLP triglyceride levels in PIO-treated IS smokers.
Conclusions:  The postprandial accumulation of RLP particles is increased in the IR subset of smokers and is likely to contribute to the increased CVD risk in these individuals. Furthermore, PIO administration provides a possible therapeutic approach to decreasing postprandial lipaemia and CVD risk in IR smokers who are unwilling or unable to stop smoking.     

Effect of a nutritional liquid supplement designed for the patient with diabetes mellitus (Glucerna SR) on the postprandial glucose state, insulin secretion and insulin sensitivity in healthy subjects

AIM: To identify the effect of a nutritional liquid supplement designed for the patient with diabetes mellitus (Glucerna SR) in single administration on the postprandial glucose state, insulin secretion and insulin sensitivity in healthy subjects. METHODS: A randomized, single-blind, cross-over, clinical trial was carried out in 14 young, healthy, non-obese, volunteers. A basal metabolic profile, which included glucose level, insulin, total cholesterol, high-density lipoprotein and low-density lipoprotein cholesterol, triglycerides, creatinine, and uric acid, was measured. Subjects received a single administration of 300 kcal, gauged with water at 350 ml, of each of the following (at least 3 days apart): glucose 75 g, polymeric supplement (Ensure high calcium) 315 ml or Glucerna SR 323 ml. At the beginning of each administration and 30, 60, 90 and 120 min later, glucose and insulin concentrations were measured. Areas under the curve of glucose and insulin were calculated. First-phase and total insulin secretions and insulin sensitivity were also estimated. RESULTS: Glucose level at 120 min was significantly lower after receiving Ensure high calcium or Glucerna SR. Administration of Glucerna SR resulted in a significant reduction in the areas under the curve of glucose and insulin, as well as in total insulin secretion with a tendency to be lower in their first phase. Insulin sensitivity was increased. CONCLUSIONS: A single administration of Glucerna SR to healthy subjects decreased the postprandial glucose and insulin states, as well as the insulin secretion; insulin sensitivity increased.     

The metabolic response to the euglycemic insulin clamp in type I diabetes and normal humans

The euglycemic insulin clamp has been utilized extensively to measure in vivo tissue sensitivity to insulin under various circumstances. Insulin sensitivity is determined from the amount of glucose metabolized under steady state conditions. To assess the effect of abnormalities in other insulin responsive metabolic pathways on glucose metabolism and thus insulin sensitivity as measured by the glucose clamp, the concentration of lactate, pyruvate, 3-hydroxybutyrate, glycerol, alanine, and free fatty acids were measured at baseline and during a two-hour euglycemic clamp in 13 nonobese subjects with type I diabetes. The observed responses were compared to 11 normal controls. Insulin sensitivity as measured by M (glucose metabolized), MCRg (metabolic clearance of glucose), and M/I ratio (glucose metabolized per unit insulin) were all significantly decreased in the diabetic subjects (P less than 0.005). Free fatty acids (FFA) and 3-hydroxybutyrate were significantly elevated at baseline in the diabetic subjects (P less than 0.05) and decreased significantly at 60 and 120 minutes in both groups. Baseline blood pyruvate and lactate concentrations were similar in the control and diabetic subjects. Pyruvate increased significantly at 60 minutes in both groups (P less than 0.05) and returned to baseline in the control subjects but remained elevated at 120 minutes in the diabetic subjects (P less than 0.001). Lactate increased similarly in both groups and remained elevated at 60 and 120 minutes. In summary, insulin sensitivity as assessed by the euglycemic insulin clamp is decreased in type I diabetes. However, specific differences in the concentration of several other metabolites both at baseline and in response to hyperinsulinemia were also identified in the diabetic subjects.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparative effects of rosuvastatin and gemfibrozil on glucose, insulin, and lipid metabolism in insulin-resistant, nondiabetic patients with combined dyslipidemia

To evaluate the pharmacologic intervention most likely to decrease cardiovascular disease risk in insulin-resistant patients with combined dyslipidemia, 39 patients with this abnormality were assessed before and after 3 months of treatment with gemfibrozil (1,200 mg/day) or rosuvastatin (40 mg/day) with regard to: (1) steady-state plasma glucose concentration at the end of a 180-minute infusion of octreotide, insulin, and glucose; (2) fasting lipid, lipoprotein, and apolipoprotein concentrations; and (3) daylong glucose, insulin, triglyceride, and remnant lipoprotein cholesterol concentrations in response to breakfast and lunch. The 2 groups were similar at baseline in age, gender, body mass index and in measurements of carbohydrate and lipoprotein metabolism. Neither gemfibrozil nor rosuvastatin enhanced insulin sensitivity or lowered daylong glucose and insulin concentrations in insulin-resistant patients with combined dyslipidemia, but both drugs significantly decreased fasting triglyceride concentrations. However, only rosuvastatin treatment significantly (p <0.05 to <0.001) reduced fasting low-density lipoprotein cholesterol, apolipoprotein B-100, apolipoprotein C-III, apolipoprotein C-III:B particles, the apolipoprotein B-100:apolipoprotein A-I ratio, and increased apolipoprotein A-I (p <0.05). The degree of improvement in fasting and postprandial remnant lipoprotein cholesterol concentrations was significantly greater (p <0.05) in rosuvastatin-treated patients, and this difference in the relative effectiveness of the drugs was also true of the decrease in non-high-density lipoprotein cholesterol concentrations.     

Biphasic insulin aspart compared to biphasic human insulin reduces postprandial hyperlipidemia in patients with Type 2 diabetes.

BACKGROUND: Premixed insulin analogues reduce postprandial hyperglycemia in patients with Type 2 diabetes in comparison to premixed regular insulin. Insulin also plays an important role in the regulation of postprandial lipid metabolism. It is known that increased levels of postprandial insulin reduce postprandial hyperlipemia but, on the other hand, no information exists with regard to the possible effect of insulin analogues in comparison to human insulin. MATERIALS AND METHODS: 12 subjects (3 men; age 59 +/- 5 years; BMI 30.5 +/- 5.9 kg/m2, duration of diabetes 9 +/- 1 years, HbA1c 8.33 +/- 1.1 %) already on therapy with premixed insulin were treated either with biphasic human insulin (BHI30) or with biphasic insulin aspart (BIAsp30) (1.3 IU fast acting insulin/12 g KH) in the setting of a standardized test meal. Serum levels of glucose, insulin, C-peptide and triglycerides as well as retinylpalmitate in plasma and chylomicron remnants were determined before and up to 8 hours after the meal. RESULTS: As was to be expected, therapy with BIAsp30 reduced the maximum increase of postprandial glucose from 7.10 +/- 2.00 mmol/l to 5.27 +/- 1.83 mmo/l (p = 0.007) compared to BHI30 insulin. In the same way, the maximum increase of triglycerides (from 2.33 +/- 1.03 to 1.65 +/- 0.69 mmol/l, p = 0.014) was reduced. The AUC 0 - 8 for triglycerides was not significantly influenced (34.20 +/- 19.86 vs. 31.46 +/- 16.21 mmol x 8 h/l) but the incremental area over baseline (AOB 0 - 8) was significantly reduced from 8.02 +/- 4.35 to 6.12 +/- 3.94 mmol x 8 h/l (p = 0.024). CONCLUSIONS: Compared to conventional human premixed insulin the prandial therapy with biphasic insulin aspart results not only in an improvement of glucose tolerance but also in a significant reduction of postprandial hyperlipemia.     

The Efficacy of Ginseng-Related Therapies in Type 2 Diabetes Mellitus: An Updated Systematic Review and Meta-analysis

Few randomized clinical trials have evaluated the efficacy of ginseng in patients with type 2 diabetes mellitus (T2DM). The current meta-analysis evaluated the ginseng-induced improvement in glucose control and insulin sensitivity in patients with type-2 diabetes or impaired glucose tolerance.Randomized clinical trials comparing ginseng supplementation versus control, in patients with T2DM or impaired glucose tolerance, were hand-searched from Medline, Cochrane, and Google Scholar databases by 2 independent reviewers using the terms “type 2 diabetes/diabetes/diabetic, impaired glucose tolerance, and ginseng/ginsenoside(s).” The primary outcome analyzed was the change in HbA1c, whereas the secondary outcomes included fasting glucose, postprandial glucose, fasting insulin, postprandial insulin, insulin resistance Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), triglycerides, total cholesterol, low density lipoprotein (LDL), and high density lipoprotein (HDL).Of the 141 studies identified, 8 studies were chosen for the current meta-analysis. The average number of patients, age, and sex distribution among the groups were comparable. Results reveal no significant difference in HbA1c levels between the ginseng supplementation and the control groups (pooled standardized difference in means = −0.148, 95% CI: −0.637 to 0.228, P = 0.355). Ginseng supplementation improved fasting glucose, postprandial insulin, and HOMA-IR levels, though no difference in postprandial glucose or fasting insulin was observed among the groups. Similarly, triglycerides, total cholesterol, and LDL levels showed significant difference between the treatment groups, while no difference in HDL was seen. In addition, ginseng-related therapy was ineffective in decreasing the fasting glucose levels in patients treated with oral hypoglycemic agents or insulin.The present results establish the benefit of ginseng supplementation in improving glucose control and insulin sensitivity in patients with T2DM or impaired glucose intolerance.     

Insulin and non-esterified fatty acid relations to alimentary lipaemia and plasma concentrations of postprandial triglyceride-rich lipoproteins in healthy middle-aged men

Aims/hypothesis. Enhanced and prolonged postprandial lipaemia is related to cardiovascular disease but how postprandial lipaemia is regulated is poorly known. We therefore determined the relations of fasting insulin concentrations to fasting and postprandial lipids, lipoproteins and non-esterified fatty acids in middle-aged men.¶Methods. The subjects, 99 healthy 50-year-old men with an apolipoprotein E3/3 genotype, ate a mixed meal. The apolipoprotein B-48 and B-100 contents were determined in triglyceride-rich lipoproteins as a measure of chylomicron remnant and very low density lipoprotein particle concentrations.¶Results. Fasting plasma insulin was associated with the triglyceride response to the test meal, independently of body mass index, waist-to-hip circumference ratio, blood glucose and the insulin effect on fasting plasma triglycerides. Exaggerated and prolonged postprandial lipaemia in subjects in the upper quartile of the plasma insulin distribution was largely accounted for by large (Svedberg flotation rate > 60) very low density lipoproteins and chylomicron remnants. Insulin relations to large postprandial triglyceride-rich lipoproteins exclusively reflected the association between plasma insulin and the fasting plasma concentrations of these lipoprotein species, whereas plasma insulin and late postprandial plasma concentrations of small (Svedberg flotation rate 20–60) chylomicron remnants were related, independently of insulin influences on fasting concentrations. Strong positive relations were found between the late increases in large triglyceride-rich lipoproteins and plasma non-esterified fatty acid concentrations after 6 h.¶Conclusion/interpretation. The degree of insulin sensitivity is a major determinant of postprandial lipaemia in healthy middle-aged men and could add to the regulation of the basal production of large triglyceride-rich lipoproteins. [Diabetologia (2000) 43: 185–193]     

尿毒症胰岛素拮抗及其在心血管病变发生中的作用

目的：探讨尿毒症胰岛素拮抗（ＩＲ）发生机理，及其在尿毒症心血管病变发生中的作用。 方法：采用口服糖耐量试验方法，检测５０例尿毒症患者和１２例正常对照者胰岛素糖代谢调节作用活性。常规检测血尿素氮、肌酐、甲状旁腺素、ｐＨ值、血碳酸氢根水平，收集尿毒症患者眼底动脉硬化、心脏扩大、主动脉硬化和髂内动脉硬化有关资料，分析ＩＲ与上述指标关系。 结果：①尿毒症组糖负荷后血糖、胰岛素水平及其曲线下面积（ＡＵＣＧ、     

Insulin resistance in obese subjects with impaired glucose tolerance. Studies with hyperinsulinemic euglycemic clamp technique

Insulin resistance is a key factor in the pathogenesis of impaired glucose tolerance (IGT) and type 2 diabetes and is also associated with greater risk for cardiovascular disease. Insulin resistance is more common in obese individuals and is considered to be the link between obesity and IGT and diabetes. The aim of the present study was to assess insulin resistance in obese subjects with IGT. We examined 57 subjects with marked overweight or obesity (BMI > > 27.8 kg x m-2), 27 with IGT and 30 with normal glucose tolerance (NGT), assessed by an oral glucose tolerance test, according to WHO criteria. Thirty lean (BMI < 25 kg x m-2) healthy subjects served as a control group. Anthropometric and biochemical parameters were measured. Insulin sensitivity was evaluated with hyperinsulinemic euglycemic clamp technique. Subjects with IGT had higher levels of glucose, insulin, non-esterified fatty acids and glycated hemoglobin than obese with NGT, all those parameters were also higher in both obese groups in comparison to controls. We showed significant differences in insulin sensitivity between the studied groups, an index of the whole-body glucose uptake was decreased in both obese groups in comparison to controls, and it was also lower in IGT than in obese NGT group. We observed marked negative correlations between insulin sensitivity and estimated anthropometric and biochemical parameters. Our study indicates that insulin resistance is an important factor determining a deterioration of glucose tolerance in subjects with overweight and obesity.     

Effects of pioglitazone in nondiabetic patients with arterial hypertension: a double-blind,placebo-controlled study

Hypertension is often associated with insulin resistance, dyslipidemia and obesity, which indicate a prediabetic state and increased risk of cardiovascular disease. Pioglitazone treatment of patients with type 2 diabetes reduces insulin resistance and improves lipid profiles. The present double-blind placebo-controlled study is the first study to report effects of pioglitazone in non-diabetic patients with arterial hypertension. Following a one week run-in, 60 patients were randomized to receive either pioglitazone (45 mg/day) or placebo for 16 weeks. Insulin sensitivity (M-value) increased by 1.2 +/- 1.7 mg/min/kg with pioglitazone compared with 0.4 +/- 1.4 mg/min/kg (P = 0.022) with placebo. HOMA index was decreased (-22.5 +/- 45.8) by pioglitazone but not by placebo (+0.8 +/- 26.5; P < 0.001). Decreases in fasting insulin and glucose were significantly (P = 0.002 and P = 0.004, respectively) greater with pioglitazone than placebo. Body weight did not change significantly with either treatment. HDL-cholesterol was increased and apolipoprotein B was decreased to a significantly greater extent with pioglitazone. There was a significantly (P = 0.016) greater decrease from baseline in diastolic blood pressure with pioglitazone. These changes would suggest improved glucose metabolism and a possible reduction in risk of cardiovascular disease with pioglitazone treatment of non-diabetic patients with arterial hypertension.     

Higher blood pressure in normoalbuminuric type 1 diabetic patients with a familial history of type 2 diabetes

BACKGROUND: To address whether type 1 diabetic patients with type 2 diabetic first degree relatives are different from others in terms of cardiovascular risk factors, insulin resistance and daily insulin dosage. METHODS: We studied 18 type 1 diabetic patients with type 2 diabetic first degree relatives and 36 type 1 diabetic patients without such relatives. Patients with diabetic complications (including microalbuminuria) were excluded. The groups were similar in terms of baseline characteristics. We measured systolic and diastolic blood pressures, body mass index, waist circumference, total cholesterol, triglycerides, LDL, VLDL, HDL, daily insulin dosage and insulin sensitivity. Insulin sensitivity was tested using insulin tolerance test. RESULTS: Type 1 diabetic patients having first degree relatives with type 2 diabetes had significantly higher systolic and diastolic blood pressures (although within the normal range) than others (p < 0.001). They were more insulin resistant according to insulin tolerance test and were using higher daily insulin dosages. In this group, waist circumference, triglyceride and VLDL levels also tended to be higher, but differences were not significant statistically. Total cholesterol, LDL and HDL levels were similar in both groups. CONCLUSION: Family history of type 2 diabetes increases blood pressure and decreases insulin sensitivity in type 1 diabetic patients. Thus such patients should be treated more aggressively in terms of both cardiovascular risk factors and glucose control.     

C-reactive protein before and after weight loss in overweight women with and without polycystic ovary syndrome

BACKGROUND: Polycystic ovary syndrome (PCOS) is associated with reproductive and metabolic abnormalities. It is unknown whether overweight women with and without PCOS achieve similar benefits from weight loss for cardiovascular risk factors. METHOD: Overweight body mass index-matched women with (n = 15) and without (n = 17) PCOS (weight, 95.3 +/- 17.6 kg; body mass index, 35.6 +/- 5.3 kg/m(2), mean +/- sd) followed an 8-wk weight loss regime. RESULTS: All subjects had similar reductions in weight (3.9 +/- 3.6 kg, 3.8%, vs. 4.5 +/- 4.1 kg, 4.7%, respectively, for PCOS and non-PCOS), waist circumference, fat mass, triglycerides, free testosterone, and fasting and postprandial insulin. At baseline, C-reactive protein (CRP) between groups was not significantly different (5.5 +/- 3.1 mg/liter for PCOS vs. 4.9 +/- 3.0 mg/liter for non-PCOS). There was a significant interaction between PCOS status and CRP (P = 0.016) such that CRP decreased with weight loss for non-PCOS women (-1.2 +/- 1.8 mg/liter; P = 0.025) but not for PCOS women. For all women, the change in CRP correlated with the change in weight (r = 0.560; P = 0.003), fat mass (r = 0.477; P = 0.016), and postprandial insulin (r = 0.402; P = 0.046). Adiponectin, IL-6, and TNF-alpha were not significantly different between groups before or after weight loss. Only subjects with baseline CRP levels below the median (4.52 mg/liter) showed increases in adiponectin (0.98 +/- 1.3 microg/liter) (P = 0.015) and greater reductions in triglycerides (P = 0.001) with weight loss. CONCLUSION: A 4-5% weight loss improved lipid, glucose, and insulin profiles in women with and without PCOS. This degree of weight loss was not effective in lowering CRP concentrations in PCOS women, suggesting that greater weight loss is required in this group to achieve equivalent cardiovascular benefit to non-PCOS women.     

Diabetic dyslipidemia

Diabetic dyslipidemia is characterized by elevated fasting and postprandial triglycerides, low HDL-cholesterol, elevated LDL-cholesterol and the predominance of small dense LDL particles. These lipid changes represent the major link between diabetes and the increased cardiovascular risk of diabetic patients. The underlying pathophysiology is only partially understood. Alterations of insulin sensitive pathways, increased concentrations of free fatty acids and low grade inflammation all play a role and result in an overproduction and decreased catabolism of triglyceride rich lipoproteins of intestinal and hepatic origin. The observed changes in HDL and LDL are mostly sequence to this. Lifestyle modification and glucose control may improve the lipid profile but statin therapy mediates the biggest benefit with respect to cardiovascular risk reduction. Therefore most diabetic patients should receive statin therapy. The role of other lipid lowering drugs, such as ezetimibe, fibrates, omega-3 fatty acids, niacin and bile acid sequestrants is less well defined as they are characterized by largely negative outcome trials. This review examines the pathophysiology of diabetic dyslipidemia and its relationship to cardiovascular diseases. Management approaches will also be discussed.     

左旋氨氯地平对原发性高血压患者胰岛素敏感性的影响

目的撅讨左旋氨氯地平对原发性高血压患者胰岛素敏感性的影响。方法将51例原发性高血压并糖耐量异常患者随机分为观察组和对照组,对照组常规使用卡托普利治疗,观察组在对照组基础上加用左旋氨氯地平2．5mg,每天1次,治疗12周比较两组血压、空腹以及餐后血糖、空腹以及餐后血胰岛素、胰岛素敏感指数（ISI）、抵抗指数（HOMA-IR）和血脂的变化。结果治疗12周观察组空腹以及餐后血糖、空腹以及餐后血胰岛素、HOMA-IR显著降低,ISI显著升高,与对照组比较差异有显著性（P〈0．05）。同时观察组收缩压和舒张压水平显著降低,与治疗前和对照组比较差异均有届著性（P〈0．05）。但血脂无显著改变。结论长效钙通道阻滞剂左旋氨氯地平对高血压患者胰岛素的敏感性具有增强作用,可改善原发性高血压患者胰岛素抵抗。     

Relationship of left ventricular mass to insulin sensitivity and body mass index in healthy individuals

OBJECTIVE: The objective of this study was to investigate the contribution of insulin resistance, hyperinsulinaemia and obesity, independently of other major factors, to changes in left ventricular mass a cardiovascular risk indicator, in a healthy population without co-morbid states such as diabetes or hypertension. METHODS AND RESULTS: This cross-sectional relational study was perfomed in 153 healthy subjects, comprising 76 men and 77 women with ages ranging from 23 to 67 years. All of them were normotensive and had a normal oral glucose tolerance test, none had cardiovascular disease and none were taking any medication. Weight, height and waist circumference were measured and BMI was calculated. A blood sample was drawn in the fasting state: plasma glucose, insulin, serum total and high density lipoprotein (HDL), low density lipoprotein cholesterol and triglycerides were measured. Insulin resistance was determined by the 'Homeostasis Assessment Model' (HOMA-IR). Subjects were studied by echocardiography. The left ventricular mass was calculated by using the anatomically validated formula of Devereux et al. RESULTS: Left ventricular mass significantly and positively correlated with BMI, age, systolic and diastolic blood pressure and fasting blood glucose. The correlation of left ventricular mass with fasting blood glucose was not maintained after controlling for BMI. BMI, fasting blood glucose, HOMA-IR, systolic and diastolic blood pressure showed significant differences with higher values for people with left ventricular hypertrophy. The logistic regression analysis showed a strong association between left ventricular hypertrophy and BMI (p < 0.05). CONCLUSION: Insulin resistance and fasting insulin is not associated with left ventricular hypertrophy in healthy people, independent of obesity. Obesity appears to be an independent risk factor for left ventricular hypertrophy.     

Salicylates increase insulin secretion in healthy obese subjects

CONTEXT: Conflicting results on the effects of salicylates on glucose tolerance in subjects with normal glucose tolerance or type 2 diabetes have been reported. OBJECTIVE: The objective of the study was to investigate the effects of a salicylate derivative (triflusal) on insulin sensitivity and insulin secretion. DESIGN, SETTING, AND PARTICIPANTS: This was a double-blind, randomized, crossover study with three treatment periods corresponding to two dose levels of triflusal and placebo in healthy obese subjects. MAIN OUTCOME MEASURES: Insulin sensitivity and insulin secretion, evaluated through frequently sampled iv glucose tolerance test that was performed after each treatment period, were measured. Insulin secretion was also evaluated in vitro in mice and human islets of Langerhans. RESULTS: The administration of triflusal led to decreased fasting serum glucose concentration in the study subjects. Insulin sensitivity did not significantly change after each treatment period. Insulin secretion, however, significantly increased in a dose-dependent fashion after each triflusal treatment period. The administration of 800 mum of the main triflusal metabolite to whole mice islets of Langerhans led to a sustained increase in intracellular calcium concentration level. This was followed by a significantly increase in insulin secretion. In human islets, 200 mum of 2-hydroxy-4-trifluoromethylbenzoic acid was sufficient to increase insulin release. CONCLUSIONS: The administration of a salicylate compound led to lowering of serum glucose concentration. We suggest that this effect was mediated through increased insulin secretion induced by salicylate directly on the beta-cell.     

Treatment of dyslipoproteinemia in the metabolic syndrome.

The metabolic syndrome consists of a cluster of metabolic disorders, many of which promote the development of atherosclerosis and increase the risk to develop cardiovascular disease. The metabolic syndrome is characterized by atherogenic dyslipidemia (elevated triglycerides, increased small dense low-density lipoproteins, and decreased high-density lipoproteins), hypertension, insulin resistance and obesity. To decrease the risk of cardiovascular disease events decreasing body weight by ingesting a healthy diet, increasing physical activity, cessation of smoking and managing dyslipidemia are recommended. Pharmacological treatment of dyslipidemia is based on different drug classes. For LDL-cholesterol-lowering mainly statins and for triglyceride-lowering mainly fibrates are used. In primary and secondary prevention trials of heart disease they have shown to reduce the incidence of coronary artery disease or coronary events by 25-60 percent. Statins reduce mainly LDL-cholesterol levels by competitive inhibition of HMG-CoA reductase but have also shown to reduce fasting and postprandial triglyceride levels. Fibrates effectively reduce fasting and postprandial lipemia, shift the distribution of LDL particles towards less dense particles and increase HDL-cholesterol. Thus fibrates particularly address components of the metabolic syndrome and features of diabetic dyslipidemia. However studies still are needed showing definite evidence on differential therapy in lipid lowering based on prospective controlled trials with endpoints of macro- and microangiopathy in diabetic patients.