Effects of metoprolol and propranolol on glucose tolerance and insulin secretion in diabetes mellitus

Twenty-two hypertensive diabetic patients were admitted to a double-blind, within-patient study, and treated with propranolol 80 mg and metoprolol 100 mg twice daily for 4 weeks according to a cross-over design. Dosages of the two drugs such as to induce comparable cardiovascular effects, did not induce relevant changes of fasting blood glucose levels in patients receiving the oral hypoglycaemic agent glibenclamide (group 1), insulin (group 2) or diet alone (group 3). Glucose tolerance, assessed with a 75 g oral load, was however decreased by propranolol, and not by metoprolol in the glibenclamide-treated group. Glucose-induced insulin secretion was reduced by propranolol and not by metoprolol both in the group treated by diet alone and in the glibenclamide-treated group. It is concluded that cardioselective metoprolol seems to be more suitable than the non-selective propranolol in the treatment of arterial hypertension in diabetic subjects, particularly when sulfonylureas are being used as hypoglycaemic agents.     

Comparative evaluation of atenolol and metoprolol on cardiovascular complications associated with streptozotocin-induced diabetic rats

Recently, various clinical studies have indicated that lipophilic beta-blockers reduce the coronary mortality in diabetic patients; however, systematic studies have not been reported. The objective of the present investigation was to compare the effects of chronic treatment with metoprolol and atenolol on cardiovascular complications in streptozotocin (STZ)-induced diabetic rats. Injection of STZ produced hyperglycemia, hypoinsulinemia, hyperlipidemia, increased blood pressure, cardiac hypertrophy, reduction in heart rate, and structural alterations in cardiac tissues. Metoprolol and atenolol effectively prevented the development of hypertension in diabetic rats. Metoprolol treatment produced a slight but significant reduction in serum glucose levels with elevation in serum insulin levels, while atenolol produced a slight increase in glucose levels but no effect on insulin levels. Moreover, neither metoprolol nor atenolol treatment reduced the elevated cholesterol levels in diabetic rats. Metoprolol treatment significantly prevented STZ-induced increase in triglyceride levels, but atenolol failed to produce this effect. Metoprolol exhibited a minimal improvement in STZ-induced bradycardia, whereas atenolol produced a further reduction in heart rate. Histological examination showed metoprolol treatment also prevented STZ-induced hypertrophy and some of the alterations in cardiomyocytes. In conclusion, our data suggest that metoprolol has some beneficial effects over atenolol with respect to cardiovascular complications associated with diabetes mellitus.     

Fetal and infant growth and cardiovascular risk factors in women.

OBJECTIVE--To examine whether cardiovascular risk factors in women are related to fetal and infant growth. DESIGN--Follow up study of women born 1923-30 whose birth weights and weights at one year were recorded. SETTING--Hertfordshire. SUBJECTS--297 women born and still living in East Hertfordshire. MAIN OUTCOME MEASURES--Plasma glucose and insulin concentrations during a standard oral glucose tolerance test; fasting plasma proinsulin and 32-33 split proinsulin concentrations; blood pressure; fasting serum total, low density lipoprotein and high density lipoprotein cholesterol, triglyceride, and apolipoprotein A I and B concentrations; and plasma fibrinogen and factor VII concentrations. RESULTS--Fasting plasma concentrations of glucose, insulin, and 32-33 split proinsulin fell with increasing birth weight (P = 0.04, P = 0.002, and P = 0.0002 respectively, when current body mass index was allowed for). Glucose and insulin concentrations 120 minutes after an oral glucose load showed similar trends (P = 0.03 and P = 0.02). Systolic blood pressure, waist:hip ratio, and serum triglyceride concentrations also fell with increasing birth weight (P = 0.08, P = 0.07, and P = 0.07 respectively), while serum high density lipoprotein cholesterol concentrations rose (P = 0.04). At each birth weight women who currently had a higher body mass index had higher levels of risk factors. CONCLUSION--In women, as in men, reduced fetal growth leads to insulin resistance and the associated disorders: raised blood pressure and high serum triglyceride and low serum high density lipoprotein cholesterol concentrations. The highest values of these coronary risk factors occur in people who were small at birth and became obese. In contrast with men, low rates of infant growth did not predict levels of risk factors in women.     

强化控糖后加用盐酸吡格列酮治疗2型糖尿病的临床疗效观察

目的观察强化控糖后加用盐酸吡格列酮治疗2型糖尿病的临床疗效。方法 60例使用口服降糖药物治疗的血糖控制不佳的2型糖尿病患者,入院后先进行胰岛素泵强化控糖治疗,患者血糖达到目标值后（FPG〈7.0 mmol/L,2 h PG〈10.0 mmol/L）,改为三餐前门冬胰岛素联合睡前甘精胰岛素继续强化治疗,1周后按1：1的比例随机分为两组,一组继续使用三餐前门冬胰岛素联合睡前甘精胰岛素治疗（对照组）,一组在三餐前门冬胰岛素联合睡前甘精胰岛素的基础上加用盐酸吡格列酮30 mg/日（治疗组）。1～4周我院住院治疗,5～12周门诊随访,若出现FPG及2 h PG明显下降或低血糖反应,则减少胰岛素用量。观察加用盐酸吡格列酮治疗前以及治疗12周时FPG、2 h PG、HbAlc、胰岛素用量、甘油三酯（TG）、总胆固醇（TC）、高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）、体重指数的变化情况。结果 （1）治疗组胰岛素用量明显下降,与加用盐酸吡格列酮治疗前有明显差异（P〈0.05）;对照组的胰岛素用量治疗前后无明显差异（P〉0.05）;（2）治疗组与对照组加用盐酸吡格列酮治疗前后FPG、2hPG均无明显差异（P〉0.05）。（3）治疗组HbAlc有所下降,与加用盐酸吡格列酮治疗前有明显差异（P〈0.05）,对照组HbAlc也有所下降,差异明显（P〈0.05）,但治疗后两组比较无明显差异（P〉0.05）。（4）加用盐酸吡格列酮后,治疗组TG下降,HDL-C升高,与同组治疗前相比,差异明显（P〈0.05）,对照组与治疗前相比差异不明显,组间比较差异有显著性（P〈0.05）。结论在强化控糖血糖达标后,加用盐酸吡格列酮继续治疗,可以明显降低患者胰岛素的使用剂量,提高患者的依从性,并且能改善血脂代谢紊乱,对于减少心血管并发症的发生有一定益处。     

Antihyperlipidemic and antidiabetic effects of umbelliferone in streptozotocin diabetic rats

The aim of the study was to evaluate blood glucose and lipid lowering effects of Umbelliferone (UMB) in streptozotocin (STZ) diabetic rats. Male albino Wistar rats (180 to 200 g) were induced diabetes by administration of STZ (40 mg/kg) intraperitonially. Normal and diabetic rats were treated with UMB in 10 percent dimethyl sulfoxide (DMSO) for 45 days. Diabetic rats had increased plasma glucose and decreased insulin, total proteins (TP), and albumin in addition to decreased food intake and body weight. Elevation in total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), very low density lipoprotein cholesterol (VLDL-C), triglycerides (TG), free fatty acids (FFA), and phospholipids (PL), and reduction in high density lipoprotein cholesterol (HDL-C) in the plasma were observed. Liver and kidney tissues of diabetic rats had elevation in the levels of TC, TG, FFA, and PL. Treatment with UMB decreased plasma glucose and increased insulin, TP, and albumin apart from food intake and body weight. In UMB-treated diabetic rats, plasma and tissue TC, TG, PL and FFA, and plasma LDL-C, VLDL-C, and HDL-C reversed to near normal. Thus, reduction of blood glucose and lipid profiles indicates that UMB has antidiabetic and antihyperlipidemic effects in diabetic rats.     

大剂量胰岛素联合西格列汀对老年2 型糖尿病患者的疗效

目的:研究大剂量胰岛素联合西格列汀对老年2型糖尿病患者的疗效。方法:选择2012年1月~2015年12月在我院进行诊治的老年2型糖尿病患者82例,随机分为两组,观察组采用大剂量胰岛素联合西格列汀治疗,对照组采用大剂量胰岛素治疗,两组均治疗3个月。比较两组治疗前后的甘油三酯、总胆固醇、低密度脂蛋白和高密度脂蛋白水平,餐后2 h血糖、空腹血糖、糖化血红蛋白,胰岛素抵抗指数、胰岛素分泌指数、每日胰岛素总量和低血糖发生次数。结果:对照组治疗前后的血脂水平无明显差异(P0.05),观察组治疗后的甘油三酯、总胆固醇和低密度脂蛋白明显降低(P0.05),高密度脂蛋白明显升高(P0.05);治疗后,两组的餐后2 h血糖、空腹血糖、糖化血红蛋白均明显降低(P0.05),且观察组降低更为明显(P0.05);对照组治疗前后的胰岛素抵抗指数、胰岛素分泌指数和每日胰岛素总量均无明显差异(P0.05),观察组治疗后的胰岛素抵抗指数和每日胰岛素总量均明显降低(P0.05),胰岛素分泌指数明显升高(P0.05);两组治疗前后低血糖发生次数和身体质量指数均无明显差异(P0.05)。结论:大剂量胰岛素联合西格列汀能有效控制老年2型糖尿病患者的血糖水平,改善胰岛β细胞功能,减少胰岛素用量,是一种安全有效的治疗方法。     

下丘脑Orexin 对肥胖大鼠能量代谢的影响

目的:探讨下丘脑注射OXR-1选择性受体拮抗剂ACT-335827对肥胖大鼠代谢的效果。方法:通过高脂饮食建立肥胖大鼠模型,采用CODA 8通道高通量非侵入性血压系统(EMKA)测量血压;所有脂类都使用商品酶试剂盒和TOSHIBA-40FR全自动分析仪测量;空腹血糖采用葡萄糖氧化酶法;空腹胰岛素采用放射免疫法测定。肥胖大鼠出现代谢紊乱后,给予ACT-335827处理,检测大鼠体重、血压、脂肪、甘油三酯、总胆固醇、高密度脂蛋白、低密度脂蛋白、游离脂肪酸(NEFA)、瘦素、空腹血糖及空腹胰岛素等的变化。结果:与普通饮食组相比,经过10周高脂饮食,高脂饮食组大鼠体重显著升高(P0.05),给予ACT-335827处理后,普通大鼠的体重、血压、脂肪含量、脂代谢等均无明显变化;与高脂饮食和高脂饮食加生理盐水处理组大鼠比较,高脂饮食加ACT-335827处理组肥胖大鼠的体重显著下降(P0.05),腹部和附睾脂肪含量下降(P0.05),低密度脂蛋白、甘油三酯、总胆固醇、瘦素水平下降(P0.05),空腹血糖及空腹胰岛素也显著降低(P0.05),但血压、肠系膜脂肪和肩胛棕色脂肪、高密度脂蛋白和NEFA无明显变化(P0.05)。结论:ACT-335827对肥胖大鼠的代谢紊乱具有改善作用,对肥胖大鼠有一定的减肥作用。     

Astaxanthin ameliorates features of metabolic syndrome in SHR/NDmcr-cp

Glucose and lipid metabolic parameters play crucial roles in metabolic syndrome and its major feature of insulin resistance. This study was designed to investigate whether dietary astaxanthin oil (ASX-O) has potential effects on metabolic syndrome features in an SHR/NDmcr-cp (cp/cp) rat model. Oral administration of ASX (50 mg/kg/day) for 22 weeks induced a significant reduction in arterial blood pressure in SHRcp. It also significantly reduced the fasting blood glucose level, homeostasis index of insulin resistance (HOMA-IR), and improved insulin sensitivity. The results also showed an improved adiponectin level, a significant increase in high-density lipoprotein cholesterol, a significant decrease in plasma levels of triglycerides, and non-esterified fatty acids. Additionally, ASX showed significant effects on the white adipose tissue by decreasing the size of the fat cells. These results suggest that ASX ameliorates insulin resistance by mechanisms involving the increase of glucose uptake, and by modulating the level of circulating lipid metabolites and adiponectin.     

有机铬、炎症与胰岛素抵抗的相关性

目的研究有机铬、炎症、他汀类药物与胰岛素抵抗,及其与心、脑血管疾病方面的关系。方法筛选40岁以上的糖耐量异常(IGT)合并高血压患者60人、糖耐量异常合并高脂血症患者60人、糖耐量异常合并冠心病患者60人和非胰岛素依赖性糖尿病(T2DM)患者60人,进行分组,每一组随机分为3个小组:2个治疗组及对照组。治疗一组在原治疗方案基础上给予唐安一号(有机铬制剂)口服,治疗二组在原治疗方案基础上给予阿乐(阿托伐他汀钙片)口服,对照组维持原治疗方案,治疗4周。结果治疗一组空腹血糖(FBG)、空腹血清胰岛素(FINS)、甘油三酯(TG)、血清总胆固醇(TC)和血清低密度脂蛋白胆固醇(LDL-C)均低于对照组(P0.05),血清高密度脂蛋白胆固醇(HDL-C)高于对照组(P0.05)。治疗二组FINS、TG、TC、LDL-C和C-反应蛋白(CRP)低于对照组(P0.05),HDL-C高于对照组(P0.05)。4周治疗后,治疗一组、治疗二组HOMA-IR均低于对照组(P0.05)。结论有机铬及他汀类药物能增强胰岛素的生物学效应,调节糖脂代谢,改善胰岛素抵抗。     

Lipid and carbohydrate metabolism in premenopausal women given subdermal estradiol implants

Fifteen premenopausal women were studied before and 6 weeks after receiving subcutaneous implants of 100 mg estradiol. Serum estradiol levels doubled; increases were also seen in fasting serum total cholesterol and in high-density lipoprotein cholesterol (HDL). This increase was confined to the HDL2 subfraction, and was not reflected in the HDL apolipoproteins. Low density lipoprotein (LDL) cholesterol levels were unchanged, as were those of apolipoprotein B, the major protein component of LDL. Carbohydrate metabolism was assessed in a subgroup of 12 women. Estrogen implantation reduced fasting plasma glucose levels but did not alter the plasma glucose response to an oral glucose tolerance test. Plasma insulin levels were unchanged both in the fasted state and during the glucose tolerance test. Our findings indicate that parenteral administration of estradiol can alter lipid and carbohydrate metabolism in premenopausal women.     

Long‐term Exercise Training in Overweight Adolescents Improves Plasma Peptide YY and Resistin

The objective of this study was to investigate the effect of long‐term exercise training on concentrations of five hormones related to appetite and insulin resistance in overweight adolescents. In addition, we were interested in the relationships of these hormones with each other and with anthropometric and/or cardiovascular disease marker changes. Participants were ≥ the 85th percentile for BMI for age and sex and participated in an 8‐month supervised aerobic training program. Anthropometrics, cardiovascular fitness assessment, and fasting blood samples were taken pre‐ and post‐training. Glucose, insulin, total cholesterol (TC), high‐density lipoprotein (HDL) cholesterol, low‐density lipoprotein (LDL) cholesterol, triglycerides, leptin, active ghrelin, total peptide YY (PYY), adiponectin, and resistin concentrations were measured. The participants increased their time to exhaustion on an incremental treadmill test and decreased both percent body fat and blood triglyceride concentrations. Total PYY concentration increased and resistin concentration decreased after long‐term exercise training, which are favorable outcomes. Leptin concentrations were related to weight, percent body fat, waist circumference, and triglyceride concentrations pre‐ and post‐training. The changes in resistin concentrations were related to the changes in triglyceride concentrations. We conclude that long‐term exercise training has beneficial effects for overweight adolescents with respect to PYY and resistin, hormones related to appetite and insulin sensitivity.     

格列美脲与沙格列汀联合治疗对2型糖尿病患者血糖控制、胰岛素抵抗及血脂的影响

目的:探讨2型糖尿病(T2DM)患者经格列美脲联合沙格列汀治疗后的临床效果,并分析其对患者血糖控制、胰岛素抵抗及血脂的影响。方法:选取我院2017年4月~2019年4月期间接收的88例T2DM患者,按乱数表法将患者分为研究组(n=44,格列美脲联合沙格列汀治疗)、对照组(n=44,沙格列汀治疗)。比较两组患者临床疗效、血糖、胰岛素抵抗及血脂指标,记录两组患者不良反应情况。结果:研究组治疗3个月后临床总有效率较对照组升高(P<0.05)。两组患者治疗3个月后空腹血糖(FBG)、餐后两小时血糖(2hPBG)、糖化血红蛋白(HbA1c)、胰岛素抵抗指数(HOMA-IR)、总胆固醇(TC)、低密度脂蛋白(LDL-C)、甘油三酯(TG)均下降,且研究组低于对照组(P<0.05)。两组患者治疗3个月后高密度脂蛋白(HDL-C)、空腹胰岛素(FINS)升高,且研究组高于对照组(P<0.05)。两组不良反应总发生率比较无差异(P>0.05)。结论:T2DM患者采用格列美脲联合沙格列汀治疗效果确切,可改善机体血脂水平及胰岛素抵抗,控制血糖水平,且用药安全性较好。     

Adrenergic mechanisms in control of plasma lipid concentrations.

The mechanisms of the changes in plasma lipids concentrations observed after beta-blockade were examined in 53 patients with hypertension receiving treatment with atenolol, metoprolol, propranolol, and oxprenolol in a randomised cross-over trial. Significant increases in mean plasma total and very-low-density lipoprotein (VLDL) triglyceride and reductions in high-density lipoprotein (HDL) cholesterol and free fatty acids concentrations wer observed with all four drugs, the increase in plasma triglyceride concentration being greatest after propranolol and oxprenolol. No significant changes were observed in total of LDL cholesterol concentrations, but HDL:LDL ratios and HDL cholesterol as a proportion of total cholesterol fell significantly. Thus plasma lipid concentrations should be monitored after three to six months of long-term treatment. Changes in triglyceride, HDL cholesterol and free fatty acid concentrations were associated with a highly significant reduction in clearance of soya oil (Intralipid) in 25 patients studied but were unrelated to changes in blood pressure. The fall in HDL cholesterol and rise in free fatty acid concentrations were significantly less in those with initially reduced HDL cholesterol or raised free fatty acid concentrations respectively. It is proposed that unopposed alpha stimulation inhibits lipoprotein lipase with a subsequent rise in plasma triglyceride and fall in HDL cholesterol concentration. Analysis of the relation between pretreatment concentrations and subsequent changes suggests that excessive alpha stimulation may impair production of HDL cholesterol in those with low HDL cholesterol concentrations before treatment. Subtle catecholamine-mediated changes in plasma lipid concentrations might provide a mechanism for the relation between stress and the development of cardiovascular events.     

Serum Lp(a) lipoprotein concentrations in insulin dependent diabetic patients with microalbuminuria.

OBJECTIVE--To compare the serum concentrations of lipoproteins and apolipoproteins in insulin dependent diabetic patients with and without microalbuminuria. DESIGN--Cross sectional study. SETTING--Paediatric and medical outpatient clinic at a university hospital. PATIENTS--76 insulin dependent diabetic patients: 41 with microalbuminuria (20 males, 21 females) and 35 controls without microalbuminuria (18 males, 17 females). The two groups were similar with respect to age, duration of disease, and haemoglobin A1c concentrations before the study. MAIN OUTCOME MEASURES--Serum concentrations of Lp(a) lipoprotein, total cholesterol, high density lipoprotein cholesterol, very low density lipoprotein cholesterol, low density lipoprotein cholesterol, triglycerides, and apolipoproteins A-I, A-II, and B. RESULTS--Median serum Lp(a) lipoprotein concentration was 10.0 mg/100 ml in the microalbuminuric group and 4.9 mg/100 ml in the control group (p = 0.007). 17 (41%) of the microalbuminuric patients and five (14%) of the control patients had Lp(a) lipoprotein values above the upper quartile of a normal population. Median serum triglycerides concentrations in the microalbuminuric and control groups were 1.15 mmol/l and 0.88 mmol/l respectively (p = 0.03). Median very low density lipoprotein cholesterol concentration was 0.52 mmol/l in the microalbuminuric group and 0.40 mmol/l in the control group (p = 0.03). No significant differences in serum concentrations of total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol, or apolipoproteins A-I, A-II, and B were found between the groups. CONCLUSIONS--Serum concentrations of Lp(a) lipoprotein are twice as high in insulin dependent diabetic patients with microalbuminuria as in those without microalbuminuria. Increased concentrations of Lp(a) lipoprotein might partly explain the increased morbidity and mortality from cardiovascular disease observed among patients with diabetic nephropathy.     

A study of the metabolism of apolipoprotein B100 in relation to insulin resistance in African American males.

The purpose of this study was to determine the relationship between insulin resistance and apoB100 metabolism in African American males. Fifteen subjects, 33 +/- 7.6 years old, were divided into two groups, insulin-resistant (IR) or insulin-sensitive (IS), based on the sum of the plasma insulin concentrations during an oral glucose tolerance test. The IR group (n = 8) differed significantly from the IS group (n = 7) with respect to body mass index (BMI) (30.1 vs 23.1 kg/m2; P = 0.0003), fasting triglycerides, (118 vs 54 mg/dl, P = 0. 013), and total plasma apolipoprotein B100 (80 vs 59 mg/dl, P = 0.014). Significantly elevated apoB100 levels in the IR group were seen in very low density lipoprotein (VLDL) (5.1 vs 3.4 mg/dl, P = 0.045) and intermediate density lipoprotein (IDL) (18 vs 12 mg/dl, P = 0.017) but not in low density lipoprotein (LDL) (57 vs 46 mg/dl, P = 0.19). Total cholesterol, high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), apolipoprotein A-I, and blood pressure were not significantly different between the two groups. There was a high correlation between the sum of insulins during the oral glucose tolerance test and the BMI (rho = 0.88, P = 0.0001). In five IR and five IS subjects, apoB100 kinetics were determined in the fasting state using a bolus dose of deuteroleucine and multicompartmental modeling. IR subjects had significantly lower fractional catabolic rates (FCR) in the larger VLDL1 (-70%), the smaller VLDL2 (-71%), and the IDL (-53%) fractions. No significant differences in production rates were observed for any lipoprotein class. There was a significant correlation between the sum of insulins and the FCR of the apoB100 of VLDL1 (rho = -0.65, P = 0.05) and of IDL (rho = -0.85, P = 0.004). The correlation coefficient of the sum of insulins and the FCR of VLDL2 was -0.61 with P = 0.067. We conclude that in this population of African American males, IR is correlated with a decreased FCR of apoB100 in VLDL and IDL and elevated plasma levels of apoB and triglycerides (TG). These changes might be explained by decreased clearance of the TG-rich lipoproteins. We postulate that this may reflect decreased lipoprotein and/or hepatic lipase activity related to insulin resistance and its association with obesity.     

Long term metabolic effects of two dietary methods of treating hyperlipidaemia.

OBJECTIVES--To compare the long term metabolic effects of two diets for treating hyperlipidaemia. DESIGN--Randomised controlled study: after three weeks of normal (control) diet, subjects were randomly allocated to one of two test diets and followed up for six months. SETTING--Lipid clinic of tertiary referral centre in Naples. SUBJECTS--63 subjects with primary type IIa and IIb hyperlipoproteinaemia entered the study, and 44 completed it. Exclusion criteria were taking drugs known to influence lipid metabolism, evidence of cardiovascular disease, homozygous familial hypercholesterolaemia, and body mass index over 30. INTERVENTIONS--Two test diets with reduced saturated fat (8%) and cholesterol (approximately 200 mg/day): one was also low in total fat and rich in carbohydrate and fibre, and the other was low in carbohydrate and fibre and rich in polyunsaturated and monounsaturated fats. MAIN OUTCOME MEASURES--Fasting plasma lipid and lipoprotein concentrations; blood glucose, insulin, and triglyceride concentrations before and after a test meal. RESULTS--In comparison with the control diet, both test diets induced significant and similar decreases in low density lipoprotein cholesterol concentrations (by a mean of 0.72 (SE 0.15) mmol/l, P < 0.001, for low total fat diet; by 0.49 (0.18) mmol/l, P < 0.05, for high unsaturated fat diet) and plasma triglyceride concentrations (by 0.21 (0.09) mmol/l, P < 0.05, for low total fat diet; by 0.39 (0.15) mmol/l, P < 0.05, for high unsaturated fat diet), while high density lipoprotein cholesterol concentrations after fasting and plasma glucose and insulin concentrations during test meals were not modified by either diet. CONCLUSIONS--Both test diets are suitable (alone or in combination) for treatment of hypercholesterolaemia.     

Intravenous glucose tolerance, insulin response to glucose, peripheral sensitivity to insulin, and serum lipoproteins in post-myocardial infarct patients with normal fasting blood glucose

Intravenous glucose tolerance (IVGTT), basal insulin and insulin response to glucose infusion (GIT), insulin sensitivity, and lipoprotein patterns were determined in non-obese post-coronary subjects, 3-6 months after myocardial infarction. Twelve had decreased and 31 normal IVGTT. The control group comprised 31 subjects with normal IVGTT, who did not display any signs of coronary disease. The post-coronary patients were not taking any drugs except for furosamide, which was shown not to influence insulin response to GIT or glucose tolerance. Decreased IVGTT in the post-coronary patients could be ascribed to decreased insulin response and insulin resistance. These two derangements are considered as hereditary markers in glucose intolerance and type 2 diabetes. Accordingly, our findings suggest that glucose intolerance in subjects with myocardial infarcts has the same background. The post-coronary patients demonstrated elevated triglycerides (TG) and cholesterol in total serum and in very low density lipoproteins (VLDL), the lipoprotein patterns being almost identical in post-coronary patients with or without decreased IVGTT. No relationship was found in the control and post-coronary groups between IVGTT, basal insulin, stimulated insulin (KI, IP), and insulin sensitivity (KG), on the one hand, and total or VLDL TG or any other lipoprotein particle, on the other. Thus, the derangements in glucose, insulin, and serum triglyceride metabolism were independent abnormalities (risk factors) in these non-obese post-coronary patients.     

Metabolic and hormonal response to physical exercise during beta 1-selective and non-selective beta-blockade

The effects of a beta 1-selective (metoprolol, 150 mg per day) and a non-selective beta-blocking agent (propranolol, 120 mg per day) on metabolic and hormonal responses to physical exercise (a 30 min bicycle ergometer test) were investigated against placebo in seven healthy male volunteers with a double blind cross-over design. The blood glucose level remained unchanged during placebo, it tended to increase during metoprolol, whereas it decreased during propranolol. Both metoprolol and propranolol counteracted the exercise-induced increase in plasma free fatty acids and caused a slight decrease in muscle glycogenolysis. The increase in blood lactate concentration during exercise was not influenced by beta-blockade. The secretion of glucagon and cortisol was not modified significantly by beta-blockade, whereas the growth hormone response to exercise was promoted equally by both beta-blocking agents. It has been assumed previously that, during treatment with beta-blocking agents, diminished hepatic gluconeogenesis, caused by the lack of lactate or free fatty acids, may result in a decline in blood glucose levels. The present results indicate that an inhibition of beta 2-mediated hepatic glycogenolysis by propranolol may also influence blood glucose homeostasis during exercise.     

Positive effects of DHEA therapy on insulin resistance and lipids in men with angiographically verified coronary heart disease--preliminary study

OBJECTIVES: The aim of this study was to analyze the influence of DHEA therapy on insulin resistance (FIRI, FG/FI) and serum lipids in men with angiographically verified coronary heart disease (CHD). MATERIAL AND METHODS: The study included thirty men aged 41-60 years (mean age 52+/-0.90 yr) with serum DHEA-S concentration<2000 microg/l, who were randomized into a double-blind, placebo-controlled, cross-over trial. Subjects completed the 80 days study of 40 days of 150 mg oral DHEA daily or placebo, and next groups were changed after 30 days of wash-out. Fasting early morning blood samples were obtained at baseline and after each treatment to determine serum hormones levels (testosterone, DHEA-S, LH, FSH estradiol and IGF-1) and also metabolic profile (total cholesterol, LDL-cholesterol, triglicerides, HDL-cholesterol, insulin, glucose, fasting insulin resistance index--FIRI and FG/FI ratio). RESULTS: Administration of DHEA was associated with 4.5-fold increase in DHEA-S levels. Relative to baseline DHEA administration resulted in a decrease in insulin levels by 40% (p<0.005) and fasting insulin resistance index (FIRI) by 47% (p<0.004). Also total cholesterol levels and LDL-cholesterol levels decreased significantly (from 222.9+/-6.6 mg/dL to 207.4+/-6.6 mg/dL and from 143.9+/-6.9 mg/dL to 130.5+/-6.0 mg/dL respectively; p<0.05). Glucose levels dropped significant below baseline values after DHEA (p<0.001). Estrogen levels significantly increased after DHEA (p<0.05). While changes of serum concentrations of testosterone, LH, FSH, IGF-I, HDL-cholesterol, triglycerides were not statistical significant. Tolerance of the treatment was good and no adverse effects were observed. CONCLUSIONS: DHEA therapy in dose of 150 mg daily during 40 days in men with DHEA levels<2000 microg/l decreased total cholesterol concentration, insulin and glucose levels and fasting insulin resistance index (FIRI). This therapy may be a beneficial against CHD risk factors.     

瑞格列奈对老年2型糖尿病胰岛β细胞功能的影响及其安全性观察

目的：评估餐时血糖调节剂瑞格列奈（商品名：诺和龙）对老年2型糖尿病（T2DM）患者胰岛β细胞早时相分泌功能的影响及其用药安全性观察。方法：符合入选的患者,完成临床和实验室检查,根据血糖水平及胰岛素释放结果给予单独瑞格列奈口服治疗12周。结果：与基础值比较,瑞格列奈治疗12周后患者餐后2h血糖（2hPG）及糖化血红蛋白（HbAlc）水平均有显著下降,差异有显著性,P〈0．05;空腹血糖（FBG）有所下降但差异无显著性,P〉0．05。治疗前后比较,患者的空腹胰岛素（FINS）水平并无明显升高,P〉0．05;Ins30、Ins60明显升高,P〈0．05;而且Ins120、Ins180有下降趋势但差异无显著性,P〉0．05。△I30／△G30比值明显升高,P〈0．05,AUCINS未见明显变化,P〉0．05。治疗前后比较患者的甘油三酯（TG）水平下降,P〈0．05,总胆固醇（TC）,低密度脂蛋白胆固醇（LDL-C）水平有所下降同时高密度脂蛋白胆固醇（HDL—C）水平略有上升,但差异无显著性P〉0．05。治疗前后患者的收缩压（SBP）及舒张压（DBP）均未见明显变化,P〉0．05。治疗过程中只有1例患者在早餐与午餐间出现轻微的低血糖的症状,当时测指尖血糖为3．3mmol／L,进食后症状缓解。应用瑞格列奈治疗后患者的肝肾功能均未见明显的异常,P〉0．05。结论：瑞格列奈治疗可部分恢复老年T2DM早期时相胰岛素分泌,是一种有效的并且耐受性好的口服降糖药。