Insulin improves fasting and postprandial lipemia in type 2 diabetes

BACKGROUND: The purpose of the investigation presented here was to study the effects of insulin therapy in type 2 diabetes mellitus (type 2 DM) not only on glycemic control but also on other components of the metabolic syndrome, including lipid metabolism, blood pressure, and body weight. METHODS: Twelve patients with type 2 DM were studied before and after replacement of sulphonylurea treatment with insulin for 4 months. RESULTS: Insulin therapy resulted in a significant decrease in fasting glucose levels by 26%; glycated hemoglobin decreased by 17% and fructosamine values by 19%. With insulin treatment, fasting plasma triglyceride levels decreased by 28% and total HDL cholesterol and HDL(3) cholesterol increased by 17 and 11%, respectively. Low-density lipoprotein (LDL) cholesterol showed no significant change. The magnitude of postprandial lipemia after ingestion of a standard fatty meal decreased by 38%. Insulin treatment was also accompanied by a 21% increase in lipoprotein lipase (LPL) activity in postheparin plasma and by a 20% increase in cholesteryl ester transfer protein (CETP) activity. Hepatic lipase activity was not changed significantly with insulin. Mean BMI decreased from 28.5+/-4.2 to 28.0+/-3.1 kg/m(2) (P=0.02), which is in keeping with the finding that peripheral insulin levels did not increase and which can be explained by the fact that the insulin regimen was combined with dietary counseling. Accordingly, blood pressure showed no significant change. CONCLUSION: Our study demonstrates that judicious replacement of sulfonylurea treatment with insulin therapy, together with dietary counseling, can result in a simultaneous improvement in the major stigmata of the metabolic syndrome, i.e. a significant improvement in glycemic control and lipid metabolism without unfavorable effects on body weight and blood pressure.     

Cilostazol, a selective type III phosphodiesterase inhibitor, decreases triglyceride and increases HDL cholesterol levels by increasing lipoprotein lipase activity in rats

Cilostazol, a selective type III phosphodiesterase inhibitor, has antiplatelet and vasodilating effects. In this study, the effects of cilostazol on lipid metabolism and lipoprotein lipase (LPL) activity were studied in rats. Cilostazol was administered orally at doses of 30 or 100 mg/kg twice a day for 1-2 weeks to rats. Cilostazol decreased the serum triglyceride level in normolipidemic rats. The serum triglyceride level was reduced and HDL cholesterol level was increased by cilostazol in streptozotocin (STZ)-induced diabetic rats. The disappearance of exogenous triglyceride was accelerated by cilostazol in normolipidemic rats. Cilostazol increased post-heparin plasma LPL activity but had no effect on hepatic triglyceride lipase activity in STZ-induced diabetic rats. Cilostazol also increased LPL activity in the heart in STZ-induced diabetic rats. These findings suggest that an increase in LPL activity is responsible for the serum triglyceride lowering and HDL cholesterol elevating effects of cilostazol in rats.     

Garlic powder, effect on plasma lipids, postprandial lipemia, low-density lipoprotein particle size, high-density lipoprotein subclass distribution and lipoprotein(a)

OBJECTIVES: To test the hypothesis that a garlic supplement alters plasma lipoproteins, postprandial lipemia, low-density lipoprotein (LDL) size and high-density lipoprotein (HDL) subclass distribution differently in 50 moderately hypercholesterolemic subjects classified as LDL subclass pattern A or B. BACKGROUND: Garlic has been variably reported to reduce or not affect plasma cholesterol values. Low-density lipoprotein pattern B is a common inherited disorder of lipoprotein metabolism that has been shown to have a significantly greater response to several lipid lowering treatments including low fat diet when compared with LDL pattern A individuals. METHODS: A double blind, randomized, placebo controlled trial in an outpatient lipid research clinic was performed and included fifty moderately hypercholesterolemic subjects (mean LDL cholesterol = 166 +/- 22 mg/dl) classified as LDL subclass pattern A (predominantly large LDL, n = 22) or B (predominantly small LDL, n = 28). Following a two-month stabilization period, subjects were randomly assigned to a placebo or 300 mg three times a day of a standardized garlic tablet for three months. RESULTS: For all subjects, LDL pattern A and B subjects combined, garlic treatment for three months resulted in no significant change in total cholesterol, LDL cholesterol, HDL cholesterol, HDL subclass distribution, postprandial triglycerides, apolipoprotein B, lipoprotein (a) (Lp[a]), LDL peak particle diameter or LDL subclass distribution. There was no significant difference in response for the same parameters among subjects classified as LDL pattern A or B with the exception of significantly greater (p = 0.01) reduction in mean peak particle diameter in pattern A subjects treated with either garlic or placebo. There was no significant change in LDL subclass distribution. CONCLUSIONS: This investigation confirms that garlic therapy has no effect on major plasma lipoproteins and further, that it has no impact on HDL subclasses, Lp(a), apolipoprotein B, postprandial triglycerides or LDL subclass distribution. Garlic may have a greater effect on LDL particle diameter in LDL pattern A compared with pattern B subjects. This difference was not reflected in other plasma lipid measurements.     

Glimepiride increases high-density lipoprotein cholesterol via increasing adiponectin levels in type 2 diabetes mellitus

The aims of the present study are to investigate the effect of glimepiride 1 mg/d on plasma adiponectin and to assess the contribution of adiponectin in changing high-density lipoprotein cholesterol (HDL-c) levels after glimepiride treatment. Forty patients with type 2 diabetes mellitus were included. Plasma adiponectin, fasting plasma glucose, insulin, hemoglobin A_1c, and cholesterol were measured at study entry and after 3 months of treatment with glimepiride. Both plasma adiponectin level (7.5 ± 4.5 vs 8.3 ± 4.5 μg/mL, P = .040) and HDL-c level increased significantly (50 ± 11 vs 53 ± 10 mg/dL, P = .041) in the all-subjects group. In the low-adiponectin group (initial plasma adiponectin level <6 μg/mL), both plasma adiponectin level (4.5 ± 0.9 vs 5.9 ± 2.0 μg/mL, P = .004) and HDL-c level increased significantly (44 ± 8 vs 49 ± 9 mg/dL, P = .011). There was no significant change in the high-adiponectin group (initial plasma adiponectin level ≥6 μg/mL). Change in plasma adiponectin level was an independent factor for change in HDL-c level after adjustment for other factors (β = .574, P = .009, R² = 0.524, P = .036). In conclusion, glimepiride improved plasma adiponectin level, especially in the subjects with type 2 diabetes mellitus with low adiponectin level before treatment, and may directly contribute to improving HDL-c level.     

Sitagliptin improves albuminuria in patients with type 2 diabetes mellitus

Introduction

The aim of the present study was to determine the effect of sitagliptin on microalbuminuria in patients with type 2 diabetes mellitus.

Materials and Methods

A total of 85 patients with type 2 diabetes mellitus (age >20 years, <80 years, hemoglobin A1c [HbA1c] <8.4%) were randomized to patients taking sitagliptin 50 mg or other oral glucose‐lowering agents. The following parameters were evaluated at 0, 3 and 6 months after the treatment: bodyweight, blood pressure, HbA1c, fasting plasma glucose, fasting plasma insulin, low‐density lipoprotein cholesterol, high‐density lipoprotein cholesterol, triglycerides, estimated glomerular filtration rate and urinary albumin excretion. The primary outcome was changes in urinary albumin excretion at 6 months.

Results

Significant and comparable falls in HbA1c and fasting plasma glucose were found in both groups. However, sitagliptin significantly reduced urinary albumin excretion within 6 months, especially in patients with high urinary albumin at baseline. A total of 27 patients with normoalbuminuria showed a reduction in urinary albumin excretion, suggesting that sitagliptin prevents the development of albuminuria. A total of 15 patients with albuminuria showed a reduction in urinary albumin excretion, suggesting the beneficial effect of sitagliptin in the early stage of diabetic nephropathy. There was a significant correlation between improvement of proteinuria and that of diastolic blood pressure.

Conclusions

The results suggested that sitagliptin improved albuminuria, in addition to improving glucose. The mechanism of the reduction of albuminuria by sitagliptin could be a direct effect, as well as an increase in active glucagon‐like peptide‐1, independently affecting blood pressure, bodyweight and glucose metabolism. This trial was registered with the University Hospital Medical Information Network (UMIN no. #000010871).     

Lack of postprandial leptin peaks in patients with type 2 diabetes mellitus

Leptin production by the adipocyte is acutely stimulated by insulin in vitro. In normal individuals, postprandial insulin peaks are not accompanied by corresponding changes in circulating leptin. Postprandial regulation of leptin in individuals with type 2 diabetes, to our knowledge, has not been previously examined in detail. We examined the effect of meals on circulating leptin levels in six patients with type 2 diabetes who were not treated with insulin and in seven normal individuals. After informed consent was obtained, all subjects were admitted to the General Clinical Research Center for 6 days. They consumed four meals daily (breakfast, lunch, dinner and snack). Eighteen blood samples were drawn between 7.40 a.m. and midnight for the determination of serum leptin, insulin and glucose levels. Postprandial peaks were clearly identifiable for glucose and insulin levels both in normal subjects and in those with type 2 diabetes. However, no postprandial peaks of leptin levels were present. Correlation analysis demonstrated a lack of correlation between leptin levels and the levels of glucose or insulin. We conclude that, in spite of the presence of postprandial insulin peaks, there are no acute changes in circulating leptin levels postprandially in patients with type 2 diabetes who are not on insulin therapy. In this regard, in-vivo regulation of leptin by meals in patients with type 2 diabetes is similar to that in normal individuals.     

Altered high-density lipoprotein composition is associated with risk for complications in type 2 diabetes mellitus in South Asian descendants: A cross-sectional,case-control study on lipoprotein subclass profiling

Background

Composition of high-density lipoproteins (HDL) is emerging as an important determinant in the development of microvascular complications in type 2 diabetes mellitus (T2DM). Dutch South Asian (DSA) individuals with T2DM display an increased risk of microvascular complications compared with Dutch white Caucasian (DwC) individuals with T2DM. In this study, we aimed to investigate whether changes in HDL composition associate with increased microvascular risk in this ethnic group and lead to new lipoprotein biomarkers.

Materials and Methods

Using ¹H nuclear magnetic resonance spectroscopy and Bruker IVDr Lipoprotein Subclass Analysis (B.I.LISA) software, plasma lipoprotein changes were determined in 51 healthy individuals (30 DwC, 21 DSA) and 92 individuals with T2DM (45 DwC, 47 DSA) in a cross-sectional, case-control study. Differential HDL subfractions were investigated using multinomial logistic regression analyses, adjusting for possible confounders including BMI and diabetes duration.

Results

We identified HDL compositional differences between healthy and diabetic individuals in both ethnic groups. Specifically, levels of apolipoprotein A2 and HDL-4 subfractions were lower in DSA compared with DwC with T2DM. Apolipoprotein A2 and HDL-4 subfractions also negatively correlated with waist circumference, waist-to-hip ratio, haemoglobin A1c, glucose levels and disease duration in DSA with T2DM, and associated with increased incidence of microvascular complications.

Conclusion

While HDL composition differed between controls and T2DM in both ethnic groups, the lower levels of lipid content in the smallest HDL subclass (HDL-4) in DSA with T2DM appeared to be more clinically relevant, with higher odds of having diabetes-related pan-microvascular complications such as retinopathy and neuropathy. These typical differences in HDL could be used as ethnicity-specific T2DM biomarkers.     

Ethanol with a mixed meal decreases the incretin levels early postprandially and increases postprandial lipemia in type 2 diabetic patients

Increased postprandial lipemia is a risk marker of cardiovascular disease (CVD). While moderate alcohol drinking is associated with a reduced risk of CVD in nondiabetic and type 2 diabetic patients, it is also known that alcohol increases postprandial triacylglycerol levels. The incretins, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1), are important hormones from the gut that enhance nutrient-stimulated insulin secretion. Their responses to a moderate alcohol dose in type 2 diabetes have not previously been studied. We sought to determine how alcohol influences postprandial lipid and incretin levels in patients with type 2 diabetes when taken in combination with a fat-rich mixed meal. Eleven patients with type 2 diabetes ingested on 3 separate days in random order 3 different meals containing: 100 g butter alone or 100 g butter in combination with 40 g alcohol and 50 g carbohydrate, or 100 g butter and 120 g carbohydrate. The meal with alcohol and 50 g carbohydrate was isocaloric to that of 120 g carbohydrate. Triacylglycerol levels were measured after separation by ultracentrifugation into a chylomicron-rich fraction with Svedberg flotation unit values (Sf) > 1,000, and a chylomicron-poor fraction with Sf < 1,000. Supplementation of a fat-rich mixed meal with alcohol in type 2 diabetic subjects suppressed GLP-1 early in the postprandial phase and increased the late triacylglycerol responses compared with the 2 other meals. In the chylomicron-rich fraction, both triacylglycerol and cholesterol were increased by alcohol. No significant differences in high-density lipoprotein (HDL)-cholesterol levels were seen. Isocaloric amounts of carbohydrate and alcohol suppressed equally the postprandial free fatty acid levels, but carbohydrate increased the postprandial glucose, GIP, and insulin levels the most. Early in the postprandial phase, alcohol suppresses the incretin responses and increases the late postprandial triacylglycerol levels in type 2 diabetic patients. Whether this reflects an alcohol-induced suppression of the incretin response, which adds to the alcohol-induced impairment of triacylglycerol clearance in type 2 diabetic patients, remains to be elucidated.     

Cisapride improves gallbladder emptying in patients with type 2 diabetes mellitus

BACKGROUND AND AIMS: Gallbladder motor function is impaired in many patients with diabetes, and may be related to cholinergic nerve damage. Cisapride is a prokinetic drug of the gastrointestinal tract and acts by releasing acetylcholine from cholinergic nerve endings. The aim of this study was to determine the effect of cisapride on gallbladder emptying in patients with type 2 diabetes mellitus (DM). METHODS: Gallbladder emptying and tests for autonomic neuropathy (AN) were performed in 27 patients with type 2 DM and in 10 healthy subjects. Gallbladder emptying was studied by using real-time ultrasonography after an overnight fast, and after the subjects received a breakfast that contained 2500 J. Gallbladder emptying was repeated after the treatment with cisapride (10 mg t.i.d.) for 1 week in all subjects. RESULTS: Abnormal gallbladder emptying was present in 14 (51.9%) patients. The residual gallbladder volume (mean +/- SEM) was higher (9.3 +/- 1.0 vs 4.6 +/- 0.6; P = 0.002), and ejection fraction was lower (57.4 +/- 4.0 vs 74.2 +/- 2.4; P = 0.015) in diabetic patients than it was in healthy subjects. Cisapride produced a reduction in fasting and residual volumes (24.6 +/- 2.4 vs 20.0 +/- 1.4; P = 0.034 and 9.3 +/- 1.0 vs 5.9 +/- 1.1; P = 0.00003, respectively), and an improvement in ejection fraction (57.4 +/- 4.0 vs 72.6 +/- 3.8; P = 0.000007). The improvement in gallbladder emptying after cisapride therapy was confined to the patients with AN (n = 13) (57.3 +/- 5.4 vs 80.4 +/- 2.9; P = 0.0017), suggesting denervation supersensitivity with an upregulation of cholinergic receptors. There was no significant change in the ejection fraction in patients without AN (57.5 +/- 6.1 vs 65.4 +/- 6.5; P = NS). Sex, duration of diabetes, peripheral neuropathy, diabetic retinopathy and serum cholesterol level did not influence gallbladder emptying. CONCLUSION: Impaired gallbladder emptying is common in patients with type 2 DM. Cisapride significantly improves gallbladder emptying in patients with autonomic neuropathy.     

血清内脏脂肪素水平在2型糖尿病患者中升高

目的探讨内脏脂肪素（visfatin）与2型糖尿病（T2DM）的关系。方法采用酶联免疫吸附试验（ELISA）测定56例T2DM患者和58例健康对照（NC）的血清visfatin水平，同时测定血压、血脂、视黄醇结合蛋白（RBP-4）、FPG、Fins水平，计算腰臀比（WHR）、BMI、胰岛素抵抗指数（HOMA-IR），并且分析以上各指标与visfatin的关系。结果Visfatin水平在T2DM组显著高于NC组（P〈0.01），其水平与WHR具有显著相关性（P〈0．05），与BMI在T2DM组具有显著相关性，而在NC组没有显著相关性（P〉0.05）；与血压、血脂、空腹血糖和空腹胰岛素水平没有显著的相关性。RBP-4的表达在两组间差异无统计学意义（P〉0.05）。结论Visfatin的表达可能在T2DM的发生和发展中具有一定的作用。     

Effect of sitagliptin therapy on postprandial lipoprotein levels in patients with type 2 diabetes

Aim: Recent studies indicate that type 2 diabetes is associated with an increased secretion of both hepatic and intestinal lipoproteins, leading to the accumulation of atherogenic triglyceride (TG)‐rich lipoproteins. Sitagliptin is a selective inhibitor of dipeptidyl peptidase‐4 that has been shown to reduce fasting and postprandial glucose levels in patients with type 2 diabetes presumably through incretin hormone‐mediated improvements in islet function. The objective of the present study is to examine the effects of treatment with sitagliptin on postprandial lipid and incretin hormone levels as well as glucose homeostasis in patients with type 2 diabetes. Methods: Thirty‐six subjects with type 2 diabetes (30 men/6 postmenopausal women with a mean age of 58.1 ± 6.4 years and a body mass index of 30.7 ± 4.9 kg/m²) were recruited in this double‐blind cross‐over study using sitagliptin 100 mg/day or placebo for a 6‐week period each, with a 4‐week washout period between the two phases. At the end of each phase of treatment, patients underwent an oral lipid tolerance test providing 35 g of fat per m² of body surface area and blood samples were taken over an 8‐h period. Results: Sitagliptin therapy significantly decreased the postprandial area under the curves (AUCs) for plasma apolipoprotein (apo)B (?5.1%, p = 0.002), apoB‐48 (?7.8%, p = 0.03), TG (?9.4%, p = 0.006), very low‐density lipoprotein (VLDL)‐cholesterol (?9.3%, p = 0.001), free fatty acids (FFAs) (?7.6%, p = 0.005) and glucose (?9.7%, p < 0.0001). Furthermore, the postprandial AUCs for plasma intact glucagon‐like peptide‐1 (+67.8%, p < 0.0001) and glucose‐dependent insulinotropic polypeptide (+67.3%, p < 0.0001) were significantly increased following treatment with sitagliptin, whereas the AUC for plasma glucagon was reduced by ?9.7% (p = 0.001) with no significant changes in the AUCs for plasma insulin and C‐peptide. Sitagliptin therapy also improved homeostasis model assessment (HOMA) index for insulin resistance (?14.6%, p = 0.01) and β‐cell function (+32.3%, p = 0.007). Conclusions: Treatment with sitagliptin for 6 weeks reduced postprandial plasma levels of TG‐rich lipoproteins of both intestinal and hepatic origin, most likely by increasing incretin hormone levels, reducing circulating plasma FFA concentrations and improving insulin sensitivity and β‐cell function.     

Vildagliptin therapy reduces postprandial intestinal triglyceride-rich lipoprotein particles in patients with type 2 diabetes

Aims/hypothesis We assessed the effects of vildagliptin, a novel dipeptidyl peptidase IV inhibitor, on postprandial lipid and lipoprotein metabolism in patients with type 2 diabetes.Subjects, materials and methods This was a single-centre, randomised, double-blind study in drug-naive patients with type 2 diabetes. Patients received vildagliptin (50 mg twice daily, n=15) or placebo (n=16) for 4 weeks. Triglyceride, cholesterol, lipoprotein, glucose, insulin, glucagon and glucagon-like peptide-1 (GLP-1) responses to a fat-rich mixed meal were determined for 8 h postprandially before and after 4 weeks of treatment.Results Relative to placebo, 4 weeks of treatment with vildagliptin decreased the AUC_0–8h for total trigyceride by 22±11% (p=0.037), the incremental AUC_0–8h (IAUC_0–8h) for total triglyceride by 85±47% (p=0.065), the AUC_0–8h for chylomicron triglyceride by 65±19% (p=0.001) and the IAUC_0–8h for chylomicron triglyceride by 91±28% (p=0.002). This was associated with a decrease in chylomicron apolipoprotein B-48 (AUC_0–8h, −1.0±0.5 mg l⁻¹ h, p=0.037) and chylomicron cholesterol (AUC_0–8h, −0.14±0.07 mmol l⁻¹ h, p=0.046). Consistent with previous studies, 4 weeks of treatment with vildagliptin also increased intact GLP-1, suppressed inappropriate glucagon secretion, decreased fasting and postprandial glucose, and decreased HbA_1c from a baseline of 6.7% (change, −0.4±0.1%, p<0.001), all relative to placebo.Conclusions/interpretation Treatment with vildagliptin for 4 weeks improves postprandial plasma triglyceride and apolipoprotein B-48-containing triglyceride-rich lipoprotein particle metabolism after a fat-rich meal. The mechanisms underlying the effects of this dipeptidyl peptidase IV inhibitor on postprandial lipid metabolism remain to be explored.     

2型糖尿病伴血脂异常患者HDL-C与内皮依赖性血管舒张功能的关系

目的探讨2型糖尿病（T2DM）血脂异常患者HDL-C对血管并发症的保护作用。方法选择无血管并发症的T2DM并血脂异常患者48例,根据HDL-C水平将T2DM患者分为两组：正常HDL组（HDL-C≥1.04mmol/L）和低HDL组（HDL-C〈1.04mmol/L）。同期,选择26例健康个体作为对照。采用高分辨血管外超声法检测肱动脉血流介导的内皮依赖性血管舒张功能（EDD）和硝酸甘油介导的内皮非依赖性血管舒张功能。结果（1）与对照组相比,正常HDL组和低HDL组BMI、FPG、2hPG、TC、TG、LDL-C明显高于对照组（P〈0.05～0.01）。低HDL组HDL-C明显低于对照组及正常HDL组（P〈0.01）,而正常HDL组HDL-C水平又低于对照组（P〈0.05）。（2）与对照组相比,正常HDL组和低HDL组EDD明显降低（P〈0.01）。与正常HDL组相比,低HDL组EDD明显降低（P〈0.01）。（3）多元线性相关分析表明,年龄、FPG、2hPG、LDL-C、HDL-C与EDD相关（P〈0.05）。结论在T2DM患者中,HDL-C对早期血管并发症具有保护作用。     

Lipids and lipoprotein(a) concentrations in Pakistani patients with type 2 diabetes mellitus

AIM: The aim of the present study was to analyze serum lipoprotein(a) [Lp(a)] levels in Pakistani patients with type 2 diabetes mellitus (DM) and to find correlations between clinical characteristics and dyslipidaemias in these patients. METHODS: Fasting blood samples were analyzed for Lp(a), total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), glucose and glycosylated haemoglobin (HbA1c) in 68 Pakistani patients with type 2 DM and 40 non-diabetic healthy control subjects. RESULTS: Lp(a) levels were significantly raised in diabetics as compared to the control group. No correlation of Lp(a) was seen with age, body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP) and fasting glucose. There was a positive correlation of BMI to SBP and DBP. There was a significant positive correlation between Lp(a) and total cholesterol and LDL-c. No correlation of Lp(a) was observed with HDL-c, triglycerides and glycosylated haemoglobin (HbA1c). CONCLUSION: The present study led us to conclude that serum Lp(a) levels are significantly raised in type 2 DM and have a positive correlation with serum total and LDL-c levels.     

Effect of the phosphodiesterase 4 inhibitor roflumilast on glucose metabolism in patients with treatment-naive, newly diagnosed type 2 diabetes mellitus

Context: The phosphodiesterase 4 inhibitor roflumilast is a first-in-class antiinflammatory treatment for severe chronic obstructive pulmonary disease (COPD) associated with chronic bronchitis and a history of frequent exacerbations. In previous clinical studies, a transient and reversible weight decrease was reported with roflumilast, suggesting the systemic actions of this drug may impact metabolism. Objective: Our objective was to investigate the effects of roflumilast on glucose homeostasis and body weight. Design and Setting: We conducted a 12-wk, randomized, double-blind, placebo-controlled multicenter study with outpatients. Patients: Patients (n = 205) with newly diagnosed type 2 diabetes mellitus (DM2) but without COPD were included in the study. Interventions: Roflumilast 500 μg or placebo was administered once daily. Primary Outcome: We evaluated mean change in blood glycated hemoglobin levels. Secondary Outcomes: We also evaluated mean change from baseline in the postmeal area under the curve (AUC) for a range of metabolic parameters. Results: Roflumilast was associated with a significantly greater reduction in glycated hemoglobin levels than placebo (least square mean = -0.45%; P < 0.0001) in patients with DM2. In the roflumilast group, postmeal AUC decreased significantly from baseline to last visit for free fatty acids, glycerol, glucose, and glucagon, whereas they slightly increased for C-peptide and insulin. In contrast to roflumilast, the glucagon AUC increased with placebo, and the insulin AUC decreased. Between-treatment analysis revealed statistically significant differences in favor of roflumilast for glucose (P = 0.0082), glycerol (P = 0.0104), and C-peptide levels (P = 0.0033). Patients in both treatment groups lost weight, although the between-treatment difference of the changes from baseline to last visit [-0.7 (0.4) kg] was not statistically significant (P = 0.0584). Conclusion: Roflumilast lowered glucose levels in patients with newly diagnosed DM2 without COPD, suggesting positive effects on glucose homoeostasis.     

Simvastatin treatment on postprandial hypertriglyceridemia in type 2 diabetes mellitus patients with combined hyperlipidemia

Recent studies have shown that statins are effective in reducing fasting low-density lipoprotein-cholesterol (LDL-C) and triglyceride levels. However, it remains unknown if treatment with statins also lowers daily postprandial triglyceride concentrations, which may promote atherogenesis in type 2 diabetes subjects. Forty-one subjects with type 2 diabetes and combined hyperlipidemia who had stable glycemic control were randomly assigned to take simvastatin 20 mg (n = 27) or a placebo (n = 14) once daily for 12 weeks. The medication dosage was doubled after 4 weeks if a subject's LDL-C was not less than 130 mg/dL. Among these participants, 24 subjects (15 on simvastatin and 9 on placebo) agreed to take a meal tolerance test with isocaloric mixed meals (carbohydrate, 52%; fat, 33%, and protein, 15% of the daily caloric intake) and daytime hourly blood sampling from 8 AM to 4 PM. Simvastatin treatment reduced the fasting total cholesterol level from 237 +/- 5 to 178 +/- 6 mg/dL (-25%), the LDL cholesterol level from 150 +/- 6 to 87 +/- 5 mg/dL (-40%), and raised high-density lipoprotein-cholesterol (HDL-C) level from 36 +/- 2 to 40 +/- 2 mg/dL (+11%) (all P <.001). Fasting and daily ambient triglyceride concentrations from 8 AM to 4 PM decreased significantly in response to simvastatin administration (P <.001), but not to the placebo (P =.305). Simvastatin treatment not only decreased total cholesterol and LDL-C levels and increased HDL-C levels effectively, it also decreased fasting, as well as daily postprandial triglyceride concentrations, but had no effect on glycemic control in type 2 diabetes subjects with combined hyperlipidemia.