Insulin secretion and glucose tolerance in non-insulin dependent diabetic patients after chronic nifedipine treatment

Summary The effect of nifedipine 40 mg·day^–1 for 3 months on glucose tolerance, insulin and C-peptide secretion after an oral glucose tolerance test (OGTT), intra-venous glucose tolerance test (IVGTT) and glucagon stimulatory test, has been studied in 8 moderately hypertensive women suffering from non-insulin dependent diabetes mellitus (NIDDM).No significant variation in glucose metabolism was noted after nifedipine treatment, except for a slight improvement in insulin secretion after OGTT at the end of the study. There was an increase in cholesterol as a collateral effect.     

Improved oral glucose tolerance following antiserotonin treatment in patients with chemical diabetes

Summary The effects of short-term treatment with either placebo or two serotonin antagonists, cyproheptadine and metergoline, on oral glucose tolerance and insulin secretion have been evaluated in normal subjects and in patients with chemical diabetes. Placebo treatment was not associated with any significant change in the parameters examined. Glucose tolerance in chemical diabetics was significantly improved both after cyproheptadine and metergoline; fasting plasma glucose was also reduced by metergoline. Treatment with the latter drug was also associated with a significant decrease in incremental glucose area in healthy subjects, which was not affected by cyproheptadine. Basal and glucose-stimulated insulin secretion were not affected by either drug in any subjects. Cyproheptadine and metergoline improve glucose metabolism in chemical diabetes probably by reducing insulin resistance. This may depend either on decreased secretion of counter-regulatory hormones or on a direct pharmacological action of the drugs on glucose utilization, possibly mediated by their common antiserotoninergic properties.     

Effects of nifedipine on insulin secretion and glucose metabolism in rats and in hypertensive type 2 (non-insulin dependent) diabetics

The effects of nifedipine (Adalat) on glucose metabolism and insulin release were studied in rats and in patients with type 2 diabetes mellitus complicated with hypertension. 1. In rats, 2.5-50 micrograms/kg of intravenous nifedipine reduced glucose tolerance and insulin release after intravenous glucose in a dose related fashion, although fasting blood sugar and insulin were not affected at 50 micrograms/kg of nifedipine. 2. Daily 20 to 60 mg of oral nifedipine for 12-75 weeks to 14 type 2 diabetics with hypertension did not affect their fasting blood glucose or hemoglobin A1. Mean glucose tolerance curve after the treatment was significantly ameliorated, although insulin response during the oral glucose loading did not show any significant change. Those results suggest firstly that there may be a difference in insulinopenic effect of nifedipine between the species, and secondly that long-term administration of nifedipine produced no adverse influence on glucose metabolism in type 2 diabetics.     

Effect of chlorpromazine on blood glucose and plasma insulin in man

Summary In three groups of normal subjects and in one group of patients with latent diabetes mellitus a study has been made of the effects of chlorpromazine (CPZ) on blood glucose and plasma insulin. CPZ 75 mg/day for 7 days did not alter the plasma insulin response after oral glucose; nor did CPZ 50 mg/day for 7 days affect the glucose assimilation rate or insulin response to glucose injection. Infusion of CPZ 50 mg in 60 min slightly increased the basal blood glucose level but had no significant effect on basal plasma insulin. The insulin/glucose ratio after the end of the infusion was significantly higher than during the period of infusion of the drug. In latent diabetic patients CPZ infusion significantly diminished the insulin/glucose ratio during an intravenous glucose tolerance test. These results suggest that, whereas prolonged treatment with low doses of CPZ did not modify glucose tolerance and glucose-stimulated pancreatic response, higher acute doses of the drug may induce hyperglycaemia and can inhibit insulin secretion both in normal man and in patients with latent diabetes mellitus.     

不同时点糖代谢异常孕妇胰岛素抵抗与β细胞功能的研究

目的:研究不同糖耐量状态人群胰岛素抵抗(IR)和β细胞分泌功能的区别.方法:收集孕前体质指数正常,无孕前合并症及妊娠期并发症,50 g葡萄糖筛查试验阳性患者504例,行口服葡萄糖耐量试验(OGTT)及胰岛素释放试验.依美国糖尿病协会(ADA)诊断标准分组,计算并比较各组胰岛素抵抗指数(HOMA-IR)、胰岛β细胞功能指数(HOMA-β)以及反映葡萄糖刺激后胰岛素最大分泌功能的△PI/△PG.结果:不同时点糖代谢异常患者胰岛素释放特征不同,组间比较差异有统计学意义.与正常组(NGT)相比,葡萄糖耐量受损(GIGT)0、1、2及妊娠期糖尿病(GDM)组HOMA-IR均有不同程度增加,HOMA-β和△PI/△PG有不同程度下降,差异有统计学意义(P＜0.01),GIGT3与GIGT1、GDM差异有统计学意义(P＜0.05),GIGT0与GDM组△PI/△PG差异有统计学意义(P＜0,01).结论:妊娠期糖代谢异常患者不仅存在IR,还有β细胞功能的受损,GIGT的不同时点血糖异常者具有不同的代谢特异性,GIGT0、GIGT1与GDM相近似,GIGT3与NGT近似.     

Effect of middle-term gliclazide treatment on insulin secretion in non-insulin dependent diabetics

Summary

Insulin secretion was studied in 12 non-insulin dependent diabetics during middle-term administration of the sulphonylurea gliclazide. Blood sugar, C-peptide and glucagon were also estimated during the intravenous glucose tolerance and arginine tests performed before and after therapy. After 3 months of gliclazide/therapy (240?mg/day) in addition to a low carbohydrate diet, the intravenous glucose tolerance test showed a significant reduction in blood sugar levels and in the partial and total areas under the blood sugar curve, as well as an improvement in early insulin secretion, characterized by a significant increase in plasma C-peptide at 4, 10 and 20 minutes. Plasma glucagon levels were not affected by the sulphonylurea therapy. In the arginine test, blood sugar levels were lower at the end of the treatment period; plasma insulin, C-peptide and glucagon did not change significantly. In this study, plasma C-peptide has proved to be a better indicator of stimulated insulin secretion than plasma insulin levels. The scarcity of hypo-glycaemic episodes during therapy with gliclazide may be related to the selective stimulation of early insulin secretion by this drug.     

白藜芦醇衍生物改善2型糖尿病大鼠血糖及胰岛素抵抗作用的研究

目的探讨白藜芦醇衍生物BTM-0512对2型糖尿病大鼠血糖及胰岛素抵抗作用的影响。方法单次腹腔注射链脲佐菌素（STZ,35mg·kg^-1）结合高脂饮食建立2型糖尿病大鼠模型。糖尿病大鼠分为3组（模型组、BTM-0512低剂量组、BTM-0512高剂量组）,药物灌胃3周。检测空腹血糖（FBG）、糖基化血红蛋白（HblAC）、空腹血清胰岛素（Fins）和口服糖耐量（OGTT）;计算HOME．IR、胰岛素敏感指数（1AD、胰岛素分泌指数（IS）,以此评价胰岛素抵抗（IR）。结果BTM-0512能剂量依赖性降低2型糖尿病大鼠FBG和HblAC,改善HOME．IR和IAI,但对OGTT与IS没有影响。结论BTM0512可以降低2型糖尿病大鼠血糖并改善IR。     

Decrease in insulin secretion related to hypocalcemia induced by a high dose of zinc in rats

A single oral administration of zinc (Zn), sufficient to induce hypocalcemia, caused a decrease in glucose tolerance in fasted rats. This decrease resulted from reduction of insulin secretion. The restoration of Zn-induced hypocalcemia completely prevented the decrease in glucose tolerance and insulin secretion. These results suggest that the effect of Zn administration on insulin secretion in rats is a consequence of hypocalcemia.     

代谢异常人群糖耐量与胰岛功能及胰岛素作用的关系

目的探讨不同糖耐量状态的代谢高危人群胰岛功能及胰岛素作用的变化。方法选择体检人群中筛查出无糖尿病史的代谢异常者334例,行口服葡萄糖耐量试验(OGTT)及胰岛素、C肽释放试验,计算胰岛素敏感指数(IAI)、胰岛素抵抗指数(IR)、胰岛素分泌指数(HBCI)和空腹β细胞功能指数(FBCI)。根据OGTT结果分为三组:糖耐量正常(NGT组,218例),糖调节受损(IGR组,93例)和糖尿病(DM组,23例),比较三组人群胰岛功能的变化。结果与NGT组比较,IGR组及DM组腰围、体重指数(BMI)、低密度脂蛋白(LDL)、胰岛素、IR升高,IAI、HBCI降低(P<0.05)。结论随糖耐量状态恶化代谢异常人群高胰岛素血症加重,胰岛素敏感性逐步降低,胰岛细胞功能呈衰退趋势。     

Nicardipine does not cause deterioration of glucose homoeostasis in man: A placebo controlled study in elderly hypertensives with and without diabetes mellitus

Summary The effect of the calcium antagonist nicardipine on insulin secretion and glucose homoeostasis was investigated in elderly hypertensives with and without diabetes mellitus; 15 patients with essential hypertension for at least 10 years and normal glucose tolerance according to standard criteria (Group I) and 15 elderly hypertensive patients affected by Type 2 diabetes mellitus and on treatment with diet or oral drugs (Group 2).In the basal state, all patients were submitted to an oral glucose tolerance test (OGTT, 75 g) and an iv arginine test (30 g), on two different days and in random order. The same tests were repeated after one month of treatment with nicardipine 60 mg/day, in three spaced doses, the last being given 1 h before the post-treatment test. Nicardipine did not change overall glucose homoestasis, as assessed by haemoglobin Alc and fructosamine, nor did it significantly affect the plasma insulin response either to glucose or arginine in Groups 1 and 2. Only the glucagon response to arginine was significantly reduced in diabetic hypertensives. Small, non-significant variations in the metabolic and hormonal parameters were seen in additional two groups of patients (Groups 3 and 4), matched with Groups 1 and 2 for age, sex and diseases, who took capsules containing placebo.Thus, nicardipine did not produce any significant over-all alteration in glucose homoestasis when given to elderly diabetic or nondiabetic hypertensive subjects.     

Association between mu-opioid receptor-1 102T>C polymorphism and intermediate type 2 diabetes phenotypes: results from the Quebec Family Study (QFS)

It has been suggested recently that molecules expressed both in the pancreas and hypothalamus, such as mu-opioid receptor 1 (OPRM1), could form an integrated brain-liver system, which may sense glucose levels and therefore contribute to the development of type 2 diabetes mellitus (T2DM). In the present study, we tested associations between OPRM1 gene polymorphisms (rs1799971, 102T/C and rs0648007G/A) and indices of glucose tolerance, insulin sensitivity (IS) and insulin secretion derived from plasma measures obtained in a fasting state and following a 75 g oral glucose tolerance test (OGTT) in 749 subjects from the Quebec Family Study (QFS). Polymorphisms were tested for association with glucose tolerance (normal vs IFG and T2DM combined) by calculating a chi(2) statistic and corresponding P values, whereas associations with quantitative measures of glucose tolerance, IS and insulin secretion were tested using mixed linear models implemented in the MIXED procedure of sas (SAS Institute, Cary, NC, USA). Associations were found between 102T/C OPRM1 and indices of glucose tolerance and IS. Compared with T/T homozygotes, carriers of the OPRM1 C-102 variant exhibited a better glucose tolerance with a lower (P = 0.006) glucose area under the curve (AUC) following the OGTT and a better IS with a higher (P = 0.03) value of the Cederholm index, a numerical index of the curve relating glucose uptake to the log(10) plasma insulin levels during the OGTT. The results of the present study reveal that the 102T/C OPRM1 gene polymorphism is associated with a better glucose tolerance and improved IS, both of which suggest a potential protective effect of this variant on T2DM risk.     

Adrenergic system and carbohydrate metabolism. Effects of beta-receptor blockade on insulin secretion and peripheral insulin sensitivity in normoglycaemic patients

Summary The effects of 3 weeks of treatment with the beta-receptor blocking agent propranolol and a placebo on glucose tolerance, insulin secretion and peripheral insulin sensitivity have been evaluated in 7 normoglycaemic hypertensive patients by an oral glucose tolerance test and the insulin clamp technique.Significant changes in systolic and diastolic blood pressure and heart rate were observed at the end of propranolol treatment, but there were no associated changes in glucose tolerance, insulin secretion or peripheral insulin sensitivity. No difference was observed in glucagon, growth hormone and free fatty acids between propranolol and placebo treatment.The results support the view that the hypothetical pancreatic glucoreceptor, at least in non-acute studies, is not affected by beta blockade. In addition, there was no effect on tissue sensitivity to insulin.     

妊娠期糖代谢异常与妊娠结局的关系

目的：了解妊娠期葡萄糖耐量变化对妊娠结局的影响。方法：对４７０例孕前无糖尿病的孕妇,进行５０ｇ葡萄糖应激试验（５０ｇＧＴ）阳性者进一步行１００ｇ口服葡萄糖耐量试验（１００ｇＯＧＴＴ）。结果５０ＧＣＴ异常的发生率为１７．０２％,妊娠期糖耐量受损（ＧＩＧＴ）的发生率为５．３１％。妊娠期糖尿病（ＧＤＭ）发生率为２．５５％,糖代谢异常患者中,巨大儿,手术产,胎膜早破,胎儿宫内窘迫及新生儿疾病等发生率显著增     

Effects of oral monosodium (L)-glutamate on insulin secretion and glucose tolerance in healthy volunteers

AIMS: To investigate the effects of glutamate on insulin secretion and glucose tolerance in humans. METHODS: Monosodium (L)-glutamate (10 g) was given orally in a double-blind placebo-controlled cross-over study to 18 healthy volunteers, aged 19-28 years, with an oral (75 g) glucose load. RESULTS: The 75 min insulin response (AUC(0,75 min)), up to tmax of glutamate kinetics, was significantly correlated with the AUC(0,75 min) of glutamate concentrations (r=0.485, P=0.049). Glucose tolerance was not affected. CONCLUSIONS: Oral (L)-glutamate enhances glucose-induced insulin secretion in healthy volunteers in a concentration-dependent manner.     

Growth hormone, insulin, and prolactin secretion in anorexia nervosa and obesity during bromocriptine treatment

We studied secretion of growth hormone (GH), insulin, and prolactin in eight women with anorexia nervosa and nine women with refractory obesity before and during treatment with bromocriptine, 10 mg/day. In the anorexic patients the raised plasma GH concentrations occurring during an oral glucose tolerance test fell significantly while on bromocriptine treatment, but there was no change in plasma insulin or blood glucose concentrations. In the obese patients, however, plasma GH concentrations remained low during the oral glucose tolerance test, and were not modified by bromocriptine. Blood glucose and plasma insulin concentrations were also unchanged. Plasma GH and plasma 11-hydroxycorticosteroid responses to insulin-induced hypoglycaemia were unaffected. Serum prolactin concentrations which were raised in five anorexic patients and marginally raised in two obese subjects, fell significantly in both groups during treatment. We observed no consistent weight changes in either groups.     

Effects of a new diuretic piretanide on glucose tolerance,insulin secretion and 125I-insulin binding

Summary The effect of a new diuretic, piretanide, on glucose tolerance, insulin secretion and ¹²⁵I-insulin binding to erythrocytes was studied in 12 male patients with mild essential hypertension. After a 4 week wash-out period with placebo, piretanide 6 mg b.i.d. was administered in a single-blind manner for 8 consecutive weeks. Although glucose tolerance deteriorated slightly in one patient, the diuretic treatment had no effect on the mean blood glucose concentrations during oral glucose tolerance tests or on glyco-haemoglobin A₁ measurements, both studies being done at 4 week intervals. Preservation of euglycemia was associated with increased insulin secretion. After 8 weeks of piretanide therapy the basal C-peptide concentration was 61% higher than the pretreatment level (0.44 vs 0.71 µU/ml; p<0.05). Glucagon — stimulated C-peptide concentrations were significantly elevated after 4 (1.67 vs 2.53 µU/ml, p<0.05) and after 8 weeks (1.67 vs. 2.90 µU/ml, p<0.01) of diuretic treatment. Fasting plasma immunoreactive insulin (IRI) levels were virtually unchanged by the drug therapy. The enhanced insulin secretion did not appear secondary to increased insulin resistance at the insulin receptor level, since the specific bound fraction of ¹²⁵I-insulin remained unaffected by diuretic treatment. Although short-term loop diuretic treatment appears to have no effect on glucose tolerance, the very low density lipoprotein synthetic rate may be promoted by the increased insulin secretion.     

Calcium antagonists and blood glucose in normal rabbits

The effects of the calcium antagonists verapamil and nifedipine on blood glucose levels, glucose tolerance, insulin secretion during glucose tolerance and hypoglycaemic effect of tolbutamide were studied in normal nondiabetic rabbits. Daily dosage of 40 mg/kg verapamil and 5 mg/kg nifedipine given orally up to 7 days did not affect blood glucose level, glucose tolerance, insulin secretion during glucose tolerance and hypoglycaemic activity of tolbutamide 250 mg/kg p.o.     

Change in glucose metabolism after long-term treatment with deflazacort and betamethasone

Summary We have compared the long-term effects of different corticosteroids on glucose metabolism by carring out a 75 g oral glucose tolerance test in 27 subjects before and after the administration of deflazacort or betamethasone for two months in random balanced sequence. Fasting plasma glucose and insulin concentrations were significantly higher after betamethasone, whereas deflazacort increased only fasting plasma insulin.After oral glucose there were significant increases in blood glucose and insulin after betamethasone compared with deflazacort. These results suggest that the degree of glucose intolerance and insulin resistance depends on the steroid used and on the dose given, although long-term treatment with deflazacort has a smaller effect on glucose metabolism than betamethasone.     

血清C肽联合糖化血红蛋白检验在糖尿病诊断中的价值分析

目的 探讨血清C肽联合糖化血红蛋白检验在糖尿病诊断中的应用价值.方法 80例糖尿病患者为研究对象,经胰岛素抵抗指数计算,将40例胰岛素抵抗的糖尿病患者设为抵抗组,40例胰岛素不抵抗糖尿病患者设为不抵抗组;将35例胰岛素分泌不足的糖尿病患者设为分泌不足组,45例胰岛素分泌正常的糖尿病患者设为分泌正常组;糖化血红蛋白异常的...     

Effect of nifedipine and nitrendipine on insulin release in non-diabetic obese patients: a double-blind, placebo-controlled study

Calcium antagonists are known to decrease insulin release in vitro. In vivo, their effects on insulin secretion and glucose tolerance are more controversial. We carried out a double-blind, double-dummy, controlled trial to study the effects of nifedipine (40 mg/day; n = 9), nitrendipine (20 mg/day; n = 9) and placebo (n = 10) on insulin release in 3 parallel groups of obese patients with mild or transient hypertension and a normal oral glucose tolerance test. The treatment lasted one week. Patients were asked not to modify their diet throughout the trial, and their body weight did not vary significantly. A 2-hour i.v. glucose tolerance test was performed twice in every patient, just before the first drug intake and one hour after the last one. The following parameters were measured or calculated during each test: basal, peak and early phase levels of blood glucose, insulin and C-peptide; glucose disappearance rate; and glucose, insulin and C-peptide incremental areas under the time-curves. On day 1, the 3 groups of patients were comparable for age, sex, body weight and every biological parameter. One-way analysis of variance did not show any significantly different evolution of those parameters between the 3 treatment groups, but calcium antagonists tended to slightly reduce the early phase of insulin release compared with placebo.