Plasma pancreatic polypeptide levels are associated with differences in body fat distribution in human subjects

Aims/hypothesis Pancreatic polypeptide (PP) is produced by the F-cells of the pancreas, and its plasma concentration has been used as a marker of parasympathetic activity. Recent work in rodents suggests that there is both sympathetic and parasympathetic innervation of white adipose tissue and that parasympathetic activity is anabolic resulting in lipid accumulation. We have examined whether in humans increased PP levels are associated with increased intra-abdominal fat (IAF), and thereby insulin resistance. Materials and methods We measured PP levels in 177 non-diabetic subjects (75 male/102 female; age 32–75 years) 3 min after an i.v. glucose bolus during a frequently sampled intravenous glucose tolerance test. IAF and s.c. fat (SCF) areas were measured by CT scan. The insulin sensitivity index (S _I) was quantified using Bergman’s minimal model. Results PP levels were higher in men than in women (96.2 ± 72.2 vs 76.1 ± 55.0 pg/ml, mean ± SD, p = 0.037), as was IAF area (124.7 ± 67.4 vs 83.0 ± 57.7 cm², p < 0.001). While PP levels were significantly associated with IAF (r = 0.16, p = 0.031), WHR (r = 0.30, p < 0.001) and age (r = 0.37, p < 0.01), they were not associated with SCF (r = 0.02, p = 0.829). The association between PP and IAF was not independent of age and/or sex. S _I was negatively associated with PP levels (r = −0.17, p = 0.026) and IAF area (r = −0.65, p < 0.001). The association between S _I and PP disappeared after adjusting for IAF area, indicating that S _I was not a major determinant of PP levels. Conclusions/interpretation In humans, age and sex may modulate the association between plasma PP level and IAF area, suggesting that they may be determinants of parasympathetic activity and thus IAF accumulation.     

Improved vascular engraftment and function of autotransplanted pancreatic islets as a result of partial pancreatectomy in the mouse and rat

Aims/hypothesis The few patients subjected to autotransplantation of pancreatic islets after pancreatectomy usually become normoglycaemic after using islets from the resected organ only, whereas allogeneic recipients usually require at least two grafts to retain normoglycaemia. Previous experimental studies have demonstrated that islets transplanted to non-pancreatectomised recipients acquire a markedly decreased blood vessel density, which leads to a hypoxic microenvironment. The aim of the present study was to test the hypothesis that autotransplanted islets have better vascular engraftment and function as a result of the pancreatic surgery involved. Materials and methods In the present study, athymic mice and inbred rats were subjected to a 60% pancreatectomy and transplanted with human or rat islets, respectively, 4 days later. Control animals underwent sham surgery. Blood flow, oxygen tension, vascular density and endocrine volume in the islet grafts were measured 1 month after transplantation. Separate grafts were used for perfusion experiments and for assessment of beta cell proliferation and endocrine cellular apoptosis at different time periods after transplantation. Results Islet grafts in partially pancreatectomised recipients had an increased blood flow, oxygen tension, blood vessel density and endocrine mass 1 month post-transplantation compared with control animals. They also exhibited increased insulin release in perfusion experiments performed 1 month post-transplantation, and decreased cellular apoptosis early after transplantation. Conclusions/interpretation The present study shows that the pancreatectomy procedure itself has beneficial effects on the engraftment of transplanted human and rat islets. Our results provide an additional explanation, besides diminished immunological responses, of the much better outcome of islet autotransplantations compared with allogeneic transplantations in the clinic.     

Aminotransferase activity in morbid and uncomplicated obesity: predictive role of fasting insulin

Background and aims.An elevation in liver enzymes and, most notably, high serum alanine aminotransferase (ALT) activity, has been correlated with metabolic syndrome and obesity. However, whether obesity per se or obesity-related co-morbidities affect aminotransferase activity is still unclear. In this study we sought to evaluate serum aminotransferase activity in morbid and uncomplicated obese subjectsMethods.In this cross-sectional study, serum aminotransferase activity, anthropometric and metabolic parameters were assessed in 290 morbid and 105 uncomplicated consecutive obese subjects matched for body mass index (BMI) (40.1 ± 6.8 vs. 39.9 ± 8.3 kg/m², respectively), age (35.9 ± 10 vs. 34.8 ± 9.6 years, respectively), sex distribution and duration of obesity.Results.Uncomplicated obese subjects showed significantly lower serum ALT activity (17.58 ± 6.3 (range 10–39) vs. 23.43 ± 16 (range 12–89) U/l, (p < 0.001)), and lower aspartate aminotransferase (AST), AST/ALT ratios and gamma-glutamyltranspeptidase (γGT) (p < 0.01 for all) than morbid obese subjects. Only 11% women and 19% men in the uncomplicated obese group showed high ALT levels, while ALT activity was high in 48% women and 51% men in the morbid obese group. Fasting insulin was the best correlate of ALT activity (R² = 0.21, p = 0.003).Conclusions.Our findings show that elevated ALT and AST activity are associated with increased fasting insulin and not with obesity per se, suggesting that the presence of insulin resistance, rather than BMI alone, plays a role in mediating the increased aminotransferase activity.     

Overnight versus 24 Hours of Continuous Subcutaneous Insulin Infusion as Supplement to Oral Antidiabetic Drugs in Type 2 Diabetes

Background

Basal continuous subcutaneous insulin infusion (CSII) therapy at a fixed rate may effectively improve glycemic control in patients with type 2 diabetes when oral antidiabetic treatment fails. Regimens of simple constant subcutaneous delivery of insulin may provide theoretical advantages in type 2 diabetes.

Methods

Ten subjects with type 2 diabetes who obtained insufficient glycemic control on oral antidiabetic drugs were included. Following an initial control day, two periods of 3 days with CSII of a rapid-acting insulin analogue, 1.5 IU/h (dose obtained from a preceding study), for 8 hours overnight and for 24 hours, respectively, were carried out in random order. Profiles of serum insulin aspart, serum endogenous insulin, and plasma glucose were recorded.

Results

Compared to the control day, an 8-hour overnight insulin infusion during a 3-day period improved fasting plasma glucose (FPG) (mean differences ± SEM; Δ59.0 ± 10.1 mg/dl; p < 0.01) and 2-hour postprandial plasma glucose (PPPG) (Δ57.8 ± 10.6 mg/dl; p < 0.01) after breakfast. Compared to an 8-hour overnight infusion, a 24-hour infusion further improved all three PPPG values after breakfast, lunch, and dinner (Δ28.8 ± 8.1 mg/dl, Δ30.6 ± 8.1 mg/dl, and Δ35.1 ± 7.9 mg/dl; p < 0.01). During insulin infusion, only one hypoglycemic episode with PG <55.8 mg/dl and mild symptoms was recorded.

Conclusion

Continuous subcutaneous insulin infusion with a rapid-acting insulin analogue at a fixed rate of 1.5 IU/h, either overnight or for 24 hours, improved glycemic control without safety concerns in patients with type 2 diabetes who had secondary failure to oral antidiabetic drugs. The effect on FPG was similar for both treatments, whereas the effect on PPPG was superior when insulin was infused during the entire 24 hours.     

2型糖尿病大鼠骨骼肌基因表达谱研究

用基因芯片技术比较2型糖尿病大鼠和正常大鼠骨骼肌基因表达谱的差异。糖尿病大鼠有157种基因下调，100种基因上调，部分基因与胰岛素抵抗、糖脂代谢相关。     

Brain energy metabolism during hypoglycaemia in healthy and Type 1 diabetic subjects

Aims/hypothesis This study aimed to examine brain energy metabolism during moderate insulin-induced hypoglycaemia in Type 1 diabetic patients and healthy volunteers.Methods Type 1 diabetic patients (mean diabetes duration 13±2.5 years; HbA₁c 6.8±0.3%) and matched controls were studied before, during (0–120 min) and after (120–240 min) hypoglycaemic (~3.0 mmol/l) hyperinsulinaemic (1.5 mU·kg^–1·min^–1) clamp tests. Brain energy metabolism was assessed by in vivo ³¹P nuclear magnetic resonance spectroscopy of the occipital lobe (3 Tesla, 10-cm surface coil).Results During hypoglycaemia, the diabetic patients showed blunted endocrine counter-regulation. Throughout the study, the phosphocreatine:-ATP ratios were lower in the diabetic patients (baseline: controls 3.08±0.29 vs diabetic patients 2.65±0.43, p<0.01; hypoglycaemia: 2.97±0.38 vs 2.60±0.35, p<0.05; recovery: 3.01±0.28 vs 2.60±0.35, p<0.01). Intracellular pH increased in both groups, being higher in diabetic patients (7.096±0.010 vs. 7.107±0.015, p<0.04), whereas intracellular magnesium concentrations decreased in both groups (controls: 377±33 vs 321±39; diabetic patients: 388±47 vs 336±68 µmol/l; p<0.05).Conclusions/interpretation Despite a lower cerebral phosphocreatine:-ATP ratio in Type 1 diabetic patients at baseline, this ratio does not change in control or diabetic patients during modest hypoglycaemia. However, both groups exhibit subtle changes in intracellular pH and intracellular magnesium concentrations.Abbreviations [Mg²⁺]_i intracellular magnesium - NMR nuclear magnetic resonance - PCr phosphocreatine - pH_i intracellular pH - P_i intracellular inorganic phosphate     

胰岛素泵入法在糖尿病伴冠心病患者酮症治疗中的应用

目的：观察门冬胰岛素泵入法在糖尿病酮症伴冠心病患者治疗中的应用价值。方法：糖尿病酮症伴冠心病患者60例,随机分为门冬胰岛素泵入组（治疗组）和常规治疗对照组,治疗组采用门冬胰岛素24h持续皮下输注基础量（根据24h胰岛素分泌特点设定每时间段的输入量）,三餐前给予负荷量;总量根据公式精确计算,基础量：占总量一半;负荷量：按血糖水平调整。对照组小剂量普通胰岛素24h持续静脉点滴,三餐前门冬胰岛素皮下注射,睡前合成胰岛素皮下注射,剂量从小剂量开始,以后随血糖水平调整。结果：两组病人酮体均转阴,但治疗组酮体转阴所需时间短（P〈0.05）,胰岛素用量少、低血糖发生率明显减低（P〈0.05）,心绞痛、心衰发生率低（P均〈0.05）。结论：胰岛素泵入法在糖尿病酮症伴冠心病患者治疗中不失为一种安全有效的好方法。     

高血压患者胰岛素抵抗与血清脂联素及炎症标志物水平

目的探讨高血压患者胰岛素抵抗与血清脂联素水平及炎症标志物变化的关系。方法入选非糖尿病的新发高血压患者108例，同时入选64例血压正常者作为对照。常规检测受试者的血压、血糖、血脂和胰岛素，计算稳态模型胰岛素抵抗指数（HOMA-1R），同时检测血清脂联素、高敏C反应蛋白（hs-CRP）、肿瘤坏死因子α（TNF-α）、白介素6（IL-6）及可溶性E选择素（sE-s）。根据血压水平对患者进行分组，比较各组血清脂联素及炎症标志物水平的差异；用logistic回归筛选平均动脉压的影响因素。结果1）HOMA-IR随着血压的升高而升高，2级和3级高血压患者与对照组比较差异有统计学意义（P〈0．05）；2）总体高血压患者血清脂联素水平（4．5&#177;2．0）mg／L低于对照组（7．1&#177;1．9）mg／L，炎症标志物hs-CRP、TNF-α、IL-6和sE-s水平高于对照组，（P均〈0．01）；3）相关分析显示脂联素与收缩压、舒张压、HOMA-IR、hs-CRP、TNF-α、IL-6和sE-s呈负相关，相关系数分别为-0．533、-0．364、-0．375、-0．234、-0．509、-0．416和-0．297（P〈0．05）；4）Logistic回归显示HOMA-IR、hs-CRP、脂联素和BMI是平均动脉压独立的影响因素（P〈0．05）。结论高血压患者血清脂联素水平低，炎症标志物水平高，存在胰岛素抵抗；随着血压水平的升高，血清脂联素水平逐渐降低，炎症标志物水平逐渐升高，胰岛素抵抗程度加重；HOMA-IR、hs-CRP、脂联素和BMI是平均动脉压独立的影响因素。     

那格列奈-静脉葡萄糖胰岛素释放试验评价2型糖尿病患者胰岛素第一时相分泌功能

目的用那格列奈-静脉葡萄糖胰岛素释放试验（NG—IVGIRT）评价新诊断的2型糖尿病（DM）患者胰岛B细胞第一时相胰岛素分泌的功能。方法8例新诊断的2型DM患者行NG—IVGIRT及普通葡萄糖胰岛素释放试验（IVGIRT）,8例正常对照行NG—IVGIRT。测定NG—IVGIRT及IVGIRT中服药前15min、注射葡萄糖前（0min）、结束时（2min）及后4、6、8、10min的胰岛素及血糖。结果2型DM患者0—10min胰岛素NG—IVGIRT明显高于IVGIRT;胰岛素曲线下面积（AUC）值NG—IVGIRT明显高于IVGIRT;血糖AUC值NG—IVGIRT明显低于IVGIRT。NG—IVGIRT0～10min胰岛素及胰岛素AUC值正常对照均显著高于2型DM,血糖AUC值正常对照明显低于2型DM。结论（1）NG—IVGIRT在某种程度上可以激发新诊断的2型DM患者第一时相胰岛素分泌的储备功能;（2）新诊断的2型DM患者NG—IVGIRT激发的第一时相胰岛素分泌的储备功能与正常对照相比仍有较大差距。