重新评估格列本脲（优降糖）最大剂量的初步研究

为研究不同格列本脲（优降糖）剂量对ＮＩＤＤＭ糖代谢及β细胞功能的影响。１７例ＮＩＤＤＭ患者，格列本脲由１０ｍｇ／天增至１５ｍｇ／天。治疗三个月后，血清格列本脲浓度升高，但空腹血糖和Ｃ肽，胰升糖素刺激后６分钟Ｃ肽，糖基化血红蛋白，胰岛素敏感指数均无改变，总胆固醇和甘油三酯亦无变化，高密度脂蛋白胆固醇轻度下降。提示有必要重新评估格列本脲的最大有效剂量。     

继发性磺脲类失效糖尿病患者胰岛素释放及外周胰岛素敏感度的研究

本文应用７５ｇ葡萄糖耐量试验对１８例继发性磺脲类药物治疗失效ＮＩＤＤＭ患者的胰岛素释放及外周胰岛素敏感度进行了测算，结果发现，继发性磺脲类失效ＮＩＤＤＭ患者的胰岛素释放和外周胰岛素敏感度均显著低于磺脲类药物治疗有效的ＮＩＤＤＭ患者及正常对照。提示继发性磺脲类失效ＮＩＤＤＭ患者存在明显的胰岛素分泌功能损害和外周胰岛素抵抗。     

NIDDM患者血浆胰岛素水平与心血管疾病危险因素的关系

ＮＩＤＤＭ患者血浆胰岛素水平与心血管疾病危险因素的关系胡玲，李春霖，潘长玉李晖，姚晨高胰岛素血症是胰岛素抵抗的重要标志，与非胰岛素依赖型糖尿病（ＮＩＤＤＭ）及其心血管并发症有密切的关系。为了探讨高胰岛素血症的病理生理意义，我们对２５５例ＮＩＤＤＭ患者...     

胰升血糖素在非胰岛素依赖型糖尿病发病机制中的作用

为探讨血浆胰升血糖素对非胰岛素信号型糖尿病发病的影响，对３２７例糖耐量 ，２５例ＮＩＤＤＭ患者和２０例经药物治疗的ＮＩＤＤＭ患者的空腹血糖，血清胰岛素和血浆胰升血糖素浓度进行了研究。     

非胰岛素依赖型糖尿病患者血清芳香酯酶的临床观察

非胰岛素依赖型糖尿病患者血清芳香酯酶的临床观察钱书虹，王诗瑾，张，刘新郑，王玉萍我们对非胰岛素依赖型糖尿病（ＮＩＤＤＭ）患者血清芳香酯酶活性的变化进行了观察，并探讨了与脂蛋白、载脂蛋白变化之间的关系，结果如下。一、对象：ＮＩＤＤＭ患者３９例（男２３例...     

肥胖和NIDDM患者EIRs变化特点及其在胰岛素抵抗中的作用

肥胖和ＮＩＤＤＭ患者ＥＩＲｓ变化特点及其在胰岛素抵抗中的作用阎德文１张建华２金之欣２肥胖和ＮＩＤＤＭ皆存在胰岛素抵抗［１，２］，细胞胰岛素受体异常可导致胰岛素抵抗［２］，这两种状态下胰岛素受体变化的特点和意义尚未完全确定。因此，我们对肥胖和ＮＩＤＤＭ...     

IDDM的强化胰岛素治疗方案是否同样适用于NIDDM

ＩＤＤＭ的强化胰岛素治疗方案是否同样适用于ＮＩＤＤＭ姚小丹，陈惠萍，王金泉关键词胰岛素依赖性糖尿病；非胰岛素依赖性糖尿病；治疗，胰岛素并发症尽管胰岛素依赖性糖尿病（ＩＤＤＭ）与非胰岛素依赖性糖尿病（ＮＩＤＤＭ）在病理生理过程上存在着明显差异，但二者在...     

依那普利对NIDDM患者糖代谢的影响

应用依那普利（２０ｍｇ／ｄ）或安慰剂对３４例不伴有高血压的非胰岛素依赖型糖尿病（ＮＩＤＤＭ）患者进行了６个月治疗，结果显示依那普利治疗后ＮＩＤＤＭ患者血糖、糖化血红蛋白、血浆胰岛素水平均明显减低，外周胰岛素敏感度显著升高，而胰岛素释放率、血压及肾功能均无明显变化。本资料表明，依那普利能够提高ＮＩＤＤＭ患者外周组织对胰岛素的利用，降低外周胰岛素抵抗，改善葡萄糖代谢     

NIDDM和IGT患者的胰岛素敏感性分析

对７１例ＮＩＤＤＭ和７８例ＩＧＴ患与６１名正常对照进行比较。结果显示：在ＩＧＴ组和ＮＩＤＤＭ组，体重指数，收缩压和舒张压，空腹血糖，血浆总胆固醇和甘油三酯均明显高于正常对照组；空腹血浆胰岛素水平，ＮＩＤＤＭ组〉ＩＧＴ组，正常对照组，而胰岛素敏感性指数（ＩＳＩ）则相反，即正常对照组〉ＩＧＴ组〉ＮＩＤＤＭ组，提示ＮＩＤＤＭ患和ＩＧＴ患伴有高胰岛素血症和胰岛素抵抗。     

依那普利对NIDD患者糖代谢的影响

应用依那普利（２０ｍｇ／ｄ）或安慰剂对３４例不伴有高血压的非胰岛素依赖型糖尿病（ＮＩＤＤＭ）患者进行了６个月治疗，结果显示依那普利治疗后ＮＩＤＤＭ患者血糖、糖化血红蛋白、血浆胰岛素水平明显减低，外周胰岛素敏感度显著升高，而胰岛素释放率、血压及肾功能均无明显变化。本资料表明，依那普利能够提高ＮＩＤＤＭ患者外周组织对胰岛素的利用，降低外周胰岛素抵抗，改善葡萄糖代谢。     

糖尿病并高血压患者高胰岛素血症初步探讨

对16例NIDDM合并高血压而无心、肾功能损害者与16例NIDDM血压正常者进行配对研究。同步检测空腹及馒头试验后血糖、胰岛素、C-肽等指标。NIDDM合并高血压组血清胰岛素水平、胰岛素/C-肽值明显高于NIDDM血压正常组,而胰岛素敏感指数则明显降低。结果表明,NIDDM合并高血压与高胰岛素血症有关,后者主要是由于肝脏对胰岛素清除率降低所致。     

Islet amyloid polypeptide (IAPP) secretion from islet cells and its plasma concentration in patients with non-insulin-dependent diabetes mellitus.

Islet amyloid polypeptide (IAPP/Amylin) is a novel peptide which was extracted from islet amyloid deposits in patients with non-insulin-dependent diabetes mellitus (NIDDM). However, its pattern of secretions and plasma concentrations under various conditions has not yet been made clear enough. In this study, we examined IAPP secretion from islet beta-cells in vitro using cultured islet cells of neonatal rat pancreas and plasma IAPP responses under various conditions in vivo in normal control subjects and patients with glucose intolerance. Our data revealed that (1) IAPP is co-secreted with insulin from islet cells of the rat pancreas by glucose and non-glucose stimuli; (2) fasting plasma IAPP levels in normal control subjects are 24.9 +/- 2.0 pg/ml and the molar ratio of IAPP/insulin is approximately 1/7; (3) fasting IAPP levels are high in obese patients and low in insulin-dependent diabetic patients, and the molar ratio of IAPP/C-peptide in NIDDM patients is lower than that in normal control subjects, suggesting the basal hyposecretion of IAPP relative to insulin in NIDDM; and (4) the obese patients who had a hyperresponsiveness of insulin relative to C-peptide had the hyperresponsiveness of IAPP relative to C-peptide during an oral glucose load, suggesting that IAPP may have some physiological effect in glucose metabolism.     

Quantitative and qualitative differences in basal and glucose- and arginine-stimulated insulin secretion in healthy subjects and different stages of NIDDM

Summary To determine quantitative and qualitative differences in insulin secretion equimolar amounts of glucose and arginine were infused in 9 healthy subjects, in 8 individuals each with obesity without and with impaired glucose tolerance, and in non-obese and obese non-insulin-dependent diabetic patients (NIDDM). Insulin secretion was calculated after individual determination of metabolic clearance rate of C-peptide (MCRcp) both as the area under the C-peptide concentration curve times MCRcp, and by a mono-compartment mathematical model, both yielding identical results. MCRcp fell consistently with increasing C-peptide infusion rate (e.g.: healthy subjects: C-peptide, 10 nmol/h, 4.2±0.4; 20 nmol/h, 3.3±0.3; 30 nmol/h, 3.1±0.2 ml/kg · min; p<0.05 to p<0.01). Basal insulin secretion was 2.1-fold greater in the obese with impaired glucose tolerance than in healthy subjects, but was unchanged in non-obese NIDDM. Glucose and arginine triggered insulin release was greater than in healthy subjects at almost identical area under the respective substrate concentration curve (AUC/kg body weight) in obese subjects without (2-fold) and with impaired glucose tolerance (4-fold), and in NIDDMs following i.v. arginine (2-fold). The mean ratio of incremental insulin release to i.v. glucose and arginine was smaller in NIDDM (normal weight, 1.3±0.4; obese, 1.0±0.2) than in healthy (2.0±0.3), or obese subjects with impaired glucose tolerance (2.8±0.7). Stimulated C-peptide/insulin ratio was reduced in all patientsvs that in healthy subjects (p<0.05). We conclude that (a) MCR of C-peptide is in part a saturable process; (b) insulin clearance may be impaired in obesity and NIDDM; and (c) insulin secretion differs in obese states and NIDDM both quantitatively and qualitatively, and thereby separates the two disorders as different entities. In addition, quantitation of insulin release in obese states may also help (d) to better define primary algorithms for insulin replacement in normal- and overweight insulin-dependent diabetic patients.     

C-peptide profiles in patients with non-insulin-dependent diabetes mellitus before and during insulin treatment.

The objective of the study was to evaluate the effect of insulin treatment on insulin secretion in patients with non-insulin-dependent diabetes mellitus (NIDDM). Ten patients with NIDDM were first investigated while still taking oral hypoglycemic agents, and then randomized to a crossover study with two eight-week periods of insulin treatment (oral treatment having been stopped) given either as mainly intermediate-acting insulin twice daily (2-dose) or as preprandial regular insulin and intermediate-acting insulin at bedtime (4-dose). In the patients treated with oral agents the 24-h C-peptide area under the curve was similar to that in the controls, but the profile was different with a rise at breakfast but with almost absent meal peaks during the rest of the day. Insulin treatment improved glycemic control markedly, lowered urinary C-peptide excretion and the serum C-peptide concentrations being reduced by more than 50%. The shape of the C-peptide profiles was unaltered and there were no significant differences between the two insulin regimens. The decrease in serum C-peptide concentration during insulin treatment correlated with the change in blood glucose. Fasting serum C-peptide concentrations correlated closely with the 24-h C-peptide area under the curve. In conclusion, insulin treatment of NIDDM patients with secondary failure to oral agents greatly reduces the insulin secretion, probably owing to the reduction in blood glucose.     

Oxidant and antioxidant systems in niddm patients: influence of vitamin E supplementation.

Free radical-mediated oxidative stress has been implicated in adverse tissue changes in a number of diseases. In view of the role of oxidative processes in non-insulin dependent diabetes mellitus (NIDDM), in this study, we investigated the oxidant and antioxidant status of plasma in patients with NIDDM and the effect of vitamin E (800 lU/day) supplementation on oxidative stress, antioxidant defense system, fructosamine levels and insulin action. Thirty controls and 40 NIDDM patients were studied. In controls and patients, plasma lipids, vitamin E, lipid peroxide, total thiols (t-SH), superoxide peroxidase (SOD) and glutathione peroxidase (GPx) were measured in the basal state and after vitamin E (800 IU/d) supplementation for a month. All lipids and lipid fractions in plasma were significantly decreased, whereas the HDL-C level was changed in diabetic patients supplemented with vitamin E when compared with baseline values. Vitamin E administration also significantly reduced fasting glucose and fructosamine levels, whereas increased significantly reduced fasting glucose and fructosamine levels, whereas increased significantly plasma C-peptide and insulin levels (p < 0.01, p < 0.001, respectively). Following vitamin E supplementation, TBARs levels were found to be significantly lower (p < 0.001) than the baseline value NIDDM patients are. On the other hand, activities of GPx and SOD were significantly higher (p < 0.001) than baseline values. A similar trend was observed for total thiols contents, but in this case, the increase was not significant. In conclusion, this study demonstrates that vitamin E improved beta-cell function and increased plasma insulin and C-peptide levels, possibly by inducing the antioxidant capacity of the organism and/or reducing the peripheral resistance in NIDDM. Long-term studies are needed to demonstrate the beneficial effects of vitamin E on treatment/prevention of NIDDM.     

Nocturnal elevation of glucose levels during fasting in noninsulin-dependent diabetes

To define the spontaneous diurnal variations in glucose regulation during fasting in noninsulin-dependent diabetes (NIDDM), we measured circulating levels of glucose, insulin, C-peptide, GH, cortisol, and glucagon at 15-min intervals in 11 patients with untreated diabetes and 7 matched control subjects studied during a 24-h period. The rates of insulin secretion were derived from the concentrations of C-peptide by deconvolution using a two-compartment mathematical model for C-peptide distribution and metabolism. In both groups of subjects, despite continued fasting, glucose levels stopped declining in the evening and subsequently rose throughout the night to reach a morning maximum. Elevated levels persisted until noon. The morning glucose maximum corresponded to a relative increase of 23.8 +/- 5.5% above the evening nadir in NIDDM patients and 13.2 +/- 4.6% in nondiabetic subjects (P less than 0.05). In NIDDM patients, insulin levels and insulin secretion rates did not parallel the nocturnal glucose changes. In contrast, in control subjects, this nocturnal glucose rise coincided with a similar increase in insulin secretion rates. Cortisol concentrations in patients with NIDDM were higher than those in control subjects throughout the study period (P less than 0.001) and rose earlier in the evening than in control subjects, thus failing to demonstrate the normal nocturnal suppression. In both groups of subjects, the nighttime glucose elevation was temporally and quantitatively correlated with the circadian cortisol rise. GH secretion was increased in the evening and nighttime periods compared to the daytime values, and in NIDDM patients, but not in control subjects, the size of the morning glucose elevation was directly related to the magnitude of this increase in GH secretion (r = 0.88; P less than 0.01). Glucagon concentrations were similar in both groups of subjects and remained essentially constant throughout the study period. We hypothesize that the nocturnal glucose rise that occurs during fasting represents a normal diurnal variation in the set-point of glucose regulation amplified by counterregulatory mechanisms activated by the fasting condition.     

Modulation of insulin secretion by insulin and glucose in type II diabetes mellitus

We studied the dose-response characteristics of insulin's ability to modulate its own secretion in normal and type II diabetic (NIDDM) subjects by measuring suppression of serum C-peptide levels during insulin infusions with the plasma glucose level held constant. In normal subjects at euglycemia, primed continuous insulin infusion rates of 15, 40, 120, and 240 mU/M2 X min acutely raised serum insulin to steady state levels of 37 +/- 2 (+/- SE), 96 +/- 6, 286 +/- 17, and 871 +/- 93 microU/ml, respectively. During each infusion, maximal suppression of C-peptide to 30% of basal levels occurred by 130 min. At the higher insulin levels (greater than or equal to 100 microU/ml), C-peptide levels fell rapidly, with an apparent t1/2 of 13 min, which approximates estimates for the t1/2 of circulating C-peptide in man. This is consistent with an immediate 70% inhibition of the basal rate of insulin secretion. At the lower insulin level (37 +/- 2 microU/ml), C-peptide levels fell to 30% of basal values less rapidly (apparent t1/2, 33 min), suggesting that 70% inhibition of basal insulin secretion rates was achieved more slowly. In NIDDM subjects, primed continuous insulin infusion rates of 15, 40, 120, and 1200 mU/M2 X min acutely raised serum insulin to steady state levels of 49 +/- 7, 93 +/- 11,364 +/- 31, and 10,003 +/- 988 microU/ml. During studies at basal hyperglycemia, only minimal C-peptide suppression was found, even at pharmacological insulin levels (10,003 +/- 988 microU/ml). However, if plasma glucose was allowed to fall during the insulin infusions, there was a rapid decrease in serum C-peptide to 30% of basal levels, analogous to that in normal subjects. Three weeks of intensive insulin therapy did not alter C-peptide suppression under conditions of hyperinsulinemia and falling plasma glucose. The following conclusions were reached. 1) In normal subjects, insulin (40-1000 microU/ml) inhibits its own secretion in a dose-responsive manner; more time is required to achieve maximal 70% suppression at the lower insulin level (40 microU/ml). 2) In NIDDM studied at basal hyperglycemia, insulin has minimal ability to suppress its own secretion. Thus, impaired feedback inhibition could contribute to basal hyperinsulinemia. 3) Under conditions of hyperinsulinemia and falling plasma glucose, insulin secretion is rapidly suppressed in NIDDM (analogous to that in normal subjects studied during euglycemia.     

Effects of spontaneous portal-systemic shunting on insulin metabolism.

Insulin degradation was measured by the C-peptide/insulin ratio in 19 patients with portal vein block with extensive spontaneous portal-systemic shunting but minimal liver cell damage: 13 patients with biopsy-proved cirrhosis and 12 controls. Blood obtained fasting and for 3 hr after oral glucose was assayed for glucose, insulin, and C-peptide. Fasting C-peptide and insulin levels in patients with portal vein block and those in controls did not differ. Eight of 13 cirrhotic patients had fasting hyperinsulinemia with a significantly reduced C-peptide/insulin ratio. After glucose administration, the C-peptide/insulin ratio in portal vein block patients with normal aspartate transaminase levels did not differ from control values. In portal vein block patients with elevated asparatate transaminase levels, the C-peptide/insulin ratio was significantly reduced only from 60 min onwards. All the cirrhotic patients showed a significantly reduced C-peptide/insulin ratio after glucose administration. It is suggested that portal-systemic shunting of blood in the presence of a normal liver does not influence hepatic insulin metabolism and that the hyperinsulinemia of cirrhosis is a feature of parenchymal liver damage. In addition, insulin degradation was abnormal in all cirrhotic patients at high insulin secretion rates, even when fasting insulin levels were normal.     

Heterogeneity of non-insulin-dependent diabetes expressed as variability in insulin sensitivity, beta-cell function and cardiovascular risk profile.

AIMS: The present study investigated the variability in insulin sensitivity and beta-cell function and their relationship to anti-glutamic acid decarboxylase (GAD) positivity and the metabolic syndrome in a group of patients with non-insulin-dependent diabetes mellitus (NIDDM). METHODS: Fifty-four subjects aged 59.5 +/- 6.1 (mean +/- SD) years with NIDDM for 7.9 +/- 3.9 years referred to hospital due to poor glycaemic control, were investigated. Insulin sensitivity was determined by the euglycaemic hyperinsulinaemic glucose clamp technique as the glucose disposal rate relative to the insulin level obtained (GDRI), and also estimated with the homeostasis model assessment (HOMA-S). beta-cell function was measured by assaying the fasting and glucagon-stimulated C-peptide levels and with the HOMA-B. RESULTS: The insulin sensitivity varied 18-fold between subjects when estimated with the clamp and six-fold when estimated with HOMA-S, and was lower the more criteria for the metabolic syndrome present (P = 0.0001 by anova). The beta-cell function varied four-fold when measured as stimulated C-peptide, and eight-fold when estimated with the HOMA-B. The levels of fasting C-peptide and HOMA-B values tended to be lower in anti-GAD+ (n = 11) than in anti-GAD-subjects (P = 0.06 and P = 0.08, respectively). From previously published coronary risk charts, we estimated the 10-year risk of a coronary heart disease (CHD) event to be > 20% in 17 of 39 patients free from cardiovascular disease at the time of study, 16 of whom qualified for a diagnosis of the metabolic syndrome. CONCLUSIONS: The wide variations in insulin sensitivity and beta-cell function found among subjects with NIDDM support the notion that the disorder is highly heterogeneous. Reduced insulin sensitivity was clearly related to the metabolic syndrome and an increased risk for CHD.     

Short- and long-term gliclazide effects on pancreatic islet cell function and hepatic insulin extraction in non-insulin-dependent diabetes mellitus.

Nine non-obese males with non-insulin-dependent diabetes mellitus (NIDDM) were evaluated before and after 3 and 12 months (6 patients) treatment with the second generation hypoglycemic sulfonylurea: gliclazide. They underwent an oral glucose tolerance test, intravenous glucose and arginine tests measuring plasma insulin and C-peptide responses. Pre-hepatic insulin production and insulin delivery to peripheral tissues were calculated by deconvolution techniques and hepatic extraction of insulin estimated. An improvement was observed in the beta-cell function of the patients on gliclazide treatment: reduction of fasting plasma glucose associated with a progressive increase in C-peptide level but insulin levels decreased at 12 months, suggesting an increase in hepatic insulin extraction at this time. In the same way, while plasma glucose values after oral and i.v. glucose were greatly reduced at 3 and 12 months treatment, insulin did not change but C-peptide levels increased significantly at 12 month treatment. While the prehepatic insulin secretion rate increased progressively on gliclazide during all glucose challenges, the fractional hepatic insulin extraction fell after 3 and increased at 12 month treatment, with opposite changes in insulin delivered to peripheral tissues. Thus the insulinogenic effect of gliclazide could be masked during long-term administration by a concomitant effect of gliclazide which increases hepatic extraction of insulin. The maintenance of the responsiveness to the non-glucose secretagogue, arginine, as evaluated by the C-peptide levels, before and after correction of hyperglycemia, suggested improvement of beta-cell sensitivity to glucose after sulfonylurea treatment.(ABSTRACT TRUNCATED AT 250 WORDS)