Blood Glucose Homeostasis in the Course of Partial Pancreatectomy – Evidence for Surgically Reversible Diabetes Induced by Cholestasis

Background and Aim

Partial pancreatic resection is accompanied not only by a reduction in the islet cell mass but also by a variety of other factors that are likely to interfere with glucose metabolism. The aim of this work was to characterize the patient dynamics of blood glucose homeostasis during the course of partial pancreatic resection and to specify the associated clinico-pathological variables.

Methods

In total, 84 individuals undergoing elective partial pancreatic resection were consecutively recruited into this observational trial. The individuals were assigned based on their fasting glucose or oral glucose tolerance testing results into one of the following groups: (I) deteriorated, (II) stable or (III) improved glucose homeostasis three months after surgery. Co-variables associated with blood glucose dynamics were identified.

Results

Of the 84 participants, 25 (30%) displayed a normal oGTT, 17 (20%) showed impaired glucose tolerance, and 10 (12%) exhibited pathological glucose tolerance. Elevated fasting glucose was present in 32 (38%) individuals before partial pancreatic resection. Three months after partial pancreatic resection, 14 (17%) patients deteriorated, 16 (19%) improved, and 54 (64%) retained stable glucose homeostasis.Stability and improvement was associated with tumor resection and postoperative normalization of recently diagnosed glucose dysregulation, preoperatively elevated tumor markers and markers for common bile duct obstruction, acute pancreatitis and liver cell damage. Improvement was linked to preoperatively elevated insulin resistance, which normalized after resection and was accompanied by a decrease in fasting- and glucose-stimulated insulin secretion.

Conclusions

Surgically reversible blood glucose dysregulation diagnosed concomitantly with a (peri-) pancreatic tumor appears secondary to compromised liver function due to tumor compression of the common bile duct and the subsequent increase in insulin resistance. It can be categorized as “cholestasis-induced diabetes” and thereby distinguished from other forms of hyperglycemic disorders.     

老年糖尿病患者牙周重度破坏后种植研究

目的:研究2型糖尿病老年患者牙周重度破坏后不同血糖水平对于牙齿种植术后炎症指标、种植体稳定性及菌斑指数的影响,探讨患者血糖控制情况和种植牙术后效果的关系。方法:选取我院2011年1月至2013年1月40例在牙周重度破坏后行种植体置入的2型糖尿病老年患者,按照术后8周糖化血红蛋白水平是否≥7.5%分为实验组和对照组,分别测定两组患者术后24小时血常规,对比其白细胞、中性粒细胞及淋巴细胞水平;同时于术后第4、8、12周检测其种植体稳定参数(ISQ);术后3个月、6个月检测其菌斑指数(PLI)。结果:术后24小时,实验组的白细胞、中性粒细胞及淋巴细胞水平显著高于对照组,P0.01;术后第4、8、12周的ISQ值,实验组显著低于对照组,P0.01;术后3个月、6个月的菌斑指数,实验组显著高于对照组,P0.01。结论:2型糖尿病老年患者牙周重度破坏后不同血糖水平与其炎症反应、种植体稳定性及细菌繁殖情况密切相关,控制术前及术后血糖,有利于提高种植体稳定性并降低术后炎症反应,减少细菌繁殖,促进尽早愈合。     

Hormonal factors influencing weight and growth pattern in craniopharyngioma

Patients operated on for craniopharyngioma frequently suffer from hyperphagia and are obese, but their statural growth is normal despite growth hormone (GH) deficiency. We have evaluated the hormonal factors influencing changes in weight and growth in 17 children before and 1, 3-6, 12, and/or 24 months after surgical resection of a craniopharyngioma performed at 7.7 +/- (SE) 1 years of age. Of these, 15 patients had a GH deficiency before surgery, and all had complete pituitary deficiency after it. The plasma fasting insulin concentrations before surgery were positively correlated with body mass index (BMI, kg/m(2); p < 0.05), plasma insulin-like growth factors (IGFI, p = 0.03, and IGFII, p = 0.04), and leptin (p = 0.03). They increased significantly 1 month after surgery and continued to increase thereafter, whereas leptin increased significantly only 3-6 months after surgery, paralleling changes in BMI. The plasma fasting insulin concentrations before surgery were also positively correlated with the weight changes (12.3 +/- 2.3 kg, p < 0.01) during the 12 months after surgery, but not with changes in BMI SDS (3.1 +/- 0.5, p = 0.07). Both expressions of weight change were correlated with the concomitant growth rates (4.8 +/- 0.7 cm, p < 0.01). IGFI was above the 10th percentile for children with idiopathic short stature in 10 of 15 patients with craniopharyngioma-induced GH deficiency and IGF-binding protein 3 in 14 of 15 patients. Craniopharyngioma itself modified the control of insulin secretion, and surgery increased the insulin secretion which continued in the same way in a given patient after surgery. The increased insulin secretion in turn increases weight and keeps IGFI nearly normal. This may explain the normal growth rate despite the complete lack of GH.     

甘精胰岛素联合不同降糖药稳定2 型糖尿病血糖水平的效果

目的:评价甘精胰岛素联合沙格列汀或格列美脲稳定2型糖尿病血糖水平的作用效果。方法:将我院2收治的228例2型糖尿病患者按照随机数字表法分为研究组和对照组,每组114人。研究组给予沙格列汀联合甘精胰岛素进行治疗,对照组给予格列美脲联合甘精胰岛素进行治疗。全部病例在治疗前4 d及治疗满16周时应用动态血糖监测仪实施72 h动态血糖监测。对比两组治疗前后血糖水平相关指标及血糖水平浮动相关指标的变化。结果:研究组治疗后体质指数显著低于对照组(P0.05)。两组治疗后空腹血糖均比本组治疗前显著下降(P0.05)。两组治疗后糖化血红蛋白均比本组治疗前显著下降(P0.05)。两组治疗后胰岛素用量无显著差异。两组平均血糖水平治疗前后无显著差异(P0.05)。研究组治疗后血糖标准差、日内血糖平均波动幅度、日内血糖波动次数、日间血糖平均绝对差改善幅度显著优于对照组。两组高血糖治疗后均比治疗前显著改善,改善幅度无显著差异(P0.05)。两组低血糖曲线下面积治疗前后无显著差异(P0.05)。结论:甘精胰岛素并用沙格列汀更能在显著控制2型糖尿病患者血糖的同时,还可使其血糖水平保持持久稳定,且不增加其低血糖的发生风险。     

Moderate effect of duodenal-jejunal bypass surgery on glucose homeostasis in patients with type 2 diabetes

Gastric bypass surgery causes resolution of type 2 diabetes (T2DM), which has led to the hypothesis that upper gastrointestinal (UGI) tract diversion, itself, improves glycemic control. The purpose of this study was to determine whether UGI tract bypass without gastric exclusion has therapeutic effects in patients with T2DM. We performed a prospective trial to assess glucose and β-cell response to an oral glucose load before and at 6, 9, and 12 months after duodenal-jejunal bypass (DJB) surgery. Thirty-five overweight or obese adults (BMI: 27.0 ± 4.0 kg/m(2)) with T2DM and 35 sex-, age-, race-, and BMI-matched subjects with normal glucose tolerance (NGT) were studied. Subjects lost weight after surgery, which was greatest at 3 months (6.9 ± 4.9%) with subsequent regain to 4.2 ± 5.3% weight loss at 12 months after surgery. Glycated hemoglobin (HbA(1c)) decreased from 9.3 ± 1.6% before to 7.7 ± 2.0% at 12 months after surgery (P < 0.001), in conjunction with a 20% decrease in the use of diabetes medications (P < 0.05); 7 (20%) subjects achieved remission of diabetes (no medications and HbA(1c) <6.5%). The area under the curve after glucose ingestion was ~20% lower for glucose but doubled for insulin and C-peptide at 12 months, compared with pre-surgery values (all P < 0.01). However, the β-cell response was still 70% lower than subjects with NGT (P < 0.001). DJB surgery improves glycemic control and increases, but does not normalize the β-cell response to glucose ingestion. These findings suggest that altering the intestinal site of delivery of ingested nutrients has moderate therapeutic effects by improving β-cell function and glycemic control.     

西格列汀对2 型糖尿病患者微量白蛋白尿影响的研究

目的:研究西格列汀对2型糖尿病患者微量白蛋白尿的影响,分析其可能机制和临床应用价值。方法:选取160例伴微量白蛋白尿的2型糖尿病患者,随机分为西格列汀组和其他药物组,各80例。比较两组患者治疗前和治疗3个月后血糖水平、尿微量白蛋白、超敏C反应蛋白及血浆还原型谷胱甘肽水平。结果:经3个月治疗,两组患者空腹血糖、餐后2 h血糖、Hb A1c均较治疗前下降,但差异无明显统计学意义(P0.05);西格列汀治疗组患者尿微量白蛋白和血浆Hs-CRP水平明显下降,血浆还原型谷胱甘肽水平明显升高,与其他口服药物治疗组相比差异具有统计学意义(P0.05)。结论:西格列汀可能通过改善机体炎症状态,降低氧化和应激水平等机制降低2型糖尿病患者的尿微量白蛋白水平。     

2型糖尿病胃肠转流术后早期肠内营养对血糖的影响

目的：探讨2型糖尿病Roux-en-Y胃肠转流术（RYGBP）后早期肠内营养对患者血糖的影响。方法：回顾2011年7月至2012年7月我科63例不同发病年龄、不同病程的2型糖尿病患者行Roux-en-Y胃肠转流术（RYGBP）后的恢复情况。共分两组：A组为术后完全肠外营养直至胃肠道功能恢复正常的患者;B组为术后早期开始肠内营养患者。监测两组患者术后3天至2周的血清白蛋白含量、血脂、肠蠕动恢复时间、血糖水平、C肽水平。结果：A、B两组术后血清白蛋白含量及血脂水平无显著性差异。B组患者肠功能恢复时间少于A组,血糖水平下降时间较A组快,其血糖下降时间与肠功能恢复时间一致,B组血清C肽水平变化时间较A组提前。结论：2型糖尿病胃肠转流术（RYGBP）后早期肠内营养支持可以促进肠道功能恢复,加快血糖水平下降,改善胰岛调节功能。     

2 型糖尿病胃肠转流术后早期肠内营养对血糖的影响

目的：探讨2 型糖尿病Roux-en-Y 胃肠转流术（RYGBP）后早期肠内营养对患者血糖的影响。方法：回顾2011 年7 月至 2012 年7 月我科63 例不同发病年龄、不同病程的2 型糖尿病患者行Roux-en-Y 胃肠转流术（RYGBP）后的恢复情况。共分两组： A 组为术后完全肠外营养直至胃肠道功能恢复正常的患者;B 组为术后早期开始肠内营养患者。监测两组患者术后3 天至2 周的 血清白蛋白含量、血脂、肠蠕动恢复时间、血糖水平、C 肽水平。结果：A、B 两组术后血清白蛋白含量及血脂水平无显著性差异。B 组患者肠功能恢复时间少于A组,血糖水平下降时间较A 组快,其血糖下降时间与肠功能恢复时间一致,B组血清C肽水平变 化时间较A 组提前。结论：2 型糖尿病胃肠转流术（RYGBP）后早期肠内营养支持可以促进肠道功能恢复,加快血糖水平下降,改 善胰岛调节功能。     

腹腔镜袖状胃切除术治疗病态性肥胖合并2型糖尿病近期疗效分析

目的:探讨行腹腔镜袖状胃切除术治疗合并2型糖尿病(type 2 diabetes mellitus,T2DM)肥胖症病人的效果。方法:回顾性分析上海长征医院普外三科2008年7月至2011年12月行腹腔镜袖状胃切除术治疗合并T2DM的肥胖症8例病人的术前资料和术后12个月的随访资料。结果:所有病人均在腹腔镜下完成手术,无中转开腹。术中术后均无严重并发症发生。在术后12个月的随访过程中,病人体重、体重指数均呈下降趋势,与术前相比,术后1月开始差异即有统计学意义(P0.01)。术后12个月T2DM临床完全缓解4例(50%),临床部分缓解4例(50%)。所有病人术后糖化血红蛋白、空腹血糖均呈下降趋势,从术后1个月开始,糖化血红蛋白与术前相比差异有统计学意义(P0.01),术后3个月复查5例(62.5%)已恢复正常水平;空腹血糖自术后1月开始与术前相比差异即有统计学意义(P0.01)。结论:腹腔镜袖状胃切除术是一种安全、有效的治疗肥胖症合并T2DM的手术方式。     

Increase in number of circulating disseminated epithelial cells after surgery for non-small cell lung cancer monitored by MAINTRAC(R) is a predictor for relapse: A preliminary report

BACKGROUND: Lung cancer still remains one of the most commonly occurring solid tumors and even in stage Ia, surgery fails in 30% of patients who develop distant metastases. It is hypothesized that these must have developed from occult circulating tumor cells present at the time of surgery, or before. The aim of the present study was to detect such cells in the peripheral blood and to monitor these cells following surgery. METHODS: 30 patients treated for lung cancer with surgery were monitored for circulating epithelial cells (CEC) by taking peripheral blood samples before, 2 weeks and 5 months after surgery and/or radiotherapy (RT) chemotherapy (CT) or combined RT/CT using magnetic bead enrichment and laser scanning cytometry (MAINTRAC(R)) for quantification of these cells. RESULTS: In 86% of the patients CEC were detected before surgery and in 100% at 2 weeks and 5 months after surgery. In the control group, which consisted of 100 normal donors without cancer, 97 % were negative for CEC. A significantly higher number of CEC was found preoperatively in patients with squamous cell carcinoma than in those with adenocarcinoma. In correlation to the extent of parenchymal manipulation 2 weeks after surgery, an increase in numbers of CEC was observed with limited resections (18/21) whereas pneumonectomy led to a decrease (5/8) of CEC, 2 weeks after surgery. The third analysis done 5 months after surgery identified 3 groups of patients. In the group of 5 patients who received neo- or adjuvant chemo/radiotherapy there was evidence that monitoring of CEC can evaluate the effects of therapy. Another group of 7 patients who underwent surgery only showed a decrease of CEC and no signs of relapse. A third group of 11 patients who had surgery only, showed an increase of CEC (4 with an initial decrease after surgery and 7 with continuous increase). In the group with a continuous increase during the following 24 months, 2 early relapses in patients with stage Ia adenocarcinoma were observed. The increase of CEC preceded clinical detection by six months. CONCLUSION: We consider, therefore, that patients with adenocarcinoma and a continuous increase of CEC after complete resection for lung cancer are at an increased risk of early relapse.     

Preoperative oral supplementation with carbohydrate and branched-chain amino acid-enriched nutrient improves insulin resistance in patients undergoing a hepatectomy: a randomized clinical trial using an artificial pancreas

Glucose metabolism is adversely affected in patients following major surgery. Patients may develop hyperglycemia due to a combination of surgical stress and postoperative insulin resistance. A randomized trial was conducted to elucidate the effect of preoperative supplementation with carbohydrates and branched-chain amino acids on postoperative insulin resistance in patients undergoing hepatic resection. A total of 26 patients undergoing a hepatectomy for the treatment of a hepatic neoplasm were randomly assigned to receive a preoperative supplement of carbohydrate and branched-chain amino acid-enriched nutrient mixture or not. The postoperative blood glucose level and the total insulin requirement for normoglycemic control during the 16 h following hepatic resection were determined using the artificial pancreas STG-22. Postoperative insulin requirements for normoglycemic control in the group with preoperative nutritional support was significantly lower than that in the control group (P = 0.039). There was no incidence of hypoglycemia (<40 mg/dL) observed in patients, including those with diabetes mellitus, when the STG-22 was used to control blood glucose levels. STG-22 is a safe and reliable tool to control postoperative glucose metabolism and evaluate insulin resistance. The preoperative oral administration of carbohydrate and branched-chain amino acid-enriched nutrient is of clinical benefit and reduces postoperative insulin resistance in patients undergoing hepatic resection.     

冠心病患者冠脉支架术后发生再狭窄的危险因素回归分析

目的:探讨冠心病患者冠脉支架手术后发生再狭窄的危险因素,为提高临床治疗效果和改善预后提供指导。方法:回顾性分析2014年1月至2015年12月我院收治的226例行冠脉支架手术的冠心病患者临床病历资料,采用SPSS21.0分析冠脉再狭窄的发生情况及危险因素。结果:51例冠心病患者冠脉支架术后发生冠脉再狭窄(22.57%)。单因素分析显示,不同吸烟史、糖尿病史、脂蛋白a(Lp(a))水平、空腹血糖、尿素氮(BUN)、总胆红素、术前病变狭窄程度、植入支架支数、长度以及直径组冠心病患者的冠脉再狭窄发生率比较,差异有统计学意义(P0.05)。多因素Logistic回归分析,吸烟史、糖尿病史、Lp(a)水平、术前病变狭窄程度、植入支架支数、长度是冠心病患者冠脉支架术后再狭窄发生的独立危险因素,OR分别为2.261、1.944、3.593、2.798、2.449、3.823,差异有统计学意义(P0.05),植入支架直径是冠脉再狭窄发生的保护因素,OR为0.261,差异有统计学意义(P0.05)。结论:冠脉植入支架的总长度、数量,术前病变的狭窄程度、Lp(a)水平、糖尿病以及吸烟是冠心病患者冠脉支架术后发生再狭窄的独立危险因素,临床应不断优化支架并根据再狭窄的危险因素采取针对性的防治措施。     

Leiomyosarcoma of the inferior vena cava level II involvement: curative resection and reconstruction of renal veins

ABSTRACT: Leiomyosarcoma of the inferior vena cava (IVCL) is a rare retroperitoneal tumor. We report two cases of level II (middle level, renal veins to hepatic veins) IVC Leiomyosarcoma, who underwent en bloc resection with reconstruction of bilateral or left renal venous return using prosthetic grafts. In our cases, IVC is documented to be occluded preoperatively, therefore, radical resection of tumor and/or right kidney was performed and the distal end of inferior vena cava was resected and without caval reconstruction. None of the patients developed edema or acute renal failure post-operatively. After surgical resection, adjuvant radiation therapy was administrated. The patients have been free of recurrence 2 years and 3 months, 9 months after surgery, respectively, indicating the complete surgical resection and radiatiotherapy contribute to the better survival. The reconstruction of inferior vena cava was not considered mandatory in level II IVC leiomyosarcoma, if the retroperitoneal venous collateral pathways have been established. In addition to the curative resection of IVC leiomyosarcoma, the renal vascular reconstruction minimized the risks of procedure-related acute renal failure, and was more physiologically preferable. This concept was reflected in the treatment of the two patients reported on.     

腹腔镜解剖性肝切除治疗肝细胞癌的临床观察

目的:探讨腹腔镜解剖性肝切除治疗肝细胞癌的临床效果及安全性。方法:选择2011年2月~2013年8月在我院进行诊治的肝细胞癌患者90例,将其随机分为治疗组与对照组,每组各45例。治疗组采用腹腔镜解剖性肝切除治疗,对照组采用开腹解剖性肝切除,两组术后都常规化疗3个月,观察和比较两组术中出血量、术后肛门排气时间和术后住院时间,并发症的发生情况及术前后血清谷氨酸转移酶(ALT)与天冬氨酸转移酶(AST)的水平。结果:与对照组相比,治疗组的术中出血量、术后肛门排气时间和术后住院时间均明显降低或缩短(P0.05),术后3个月的膈下积液、切口感染、肺部感染、胆漏的发生率明显降低(P0.05)。两组术前血清ALT与AST值对比差异无统计学意义(P0.05);术后1周,两组的ALT与AST值都明显升上(P0.05);术后3个月,治疗组的ALT与AST值明显低于对照组(P0.05)。所有患者随访到2015年8月,治疗组的中位生存期为(18.33±3.11)个月,而对照组为(12.46±2.19)个月,较治疗组明显缩短(P0.05)。结论:腹腔镜解剖性肝切除治疗肝细胞癌具有更好的微创性,能减少近期并发症的发生,促进肝功能的恢复,且能够延长患者的生存时间。     

Effect of bread containing resistant starch on postprandial blood glucose levels in humans

We examined the inhibitory effect of a single ingestion of bread containing resistant starch (bread containing about 6 g of resistant starch derived from tapioca per 2 slices) (test food) on the postprandial increase in blood glucose in male and female adults with a fasting blood glucose level between 100 and 140 mg/dl. Bread not containing resistant starch (placebo) was used as the control.The study was conducted in 20 subjects (9 men and 11 women with a mean age of 50.5+/-7.5 years) using the crossover method, with a single ingestion of either bread containing resistant starch or the placebo. Blood glucose and insulin were measured before ingestion, and at 0.5, 1, 1.5, and 2 h after ingestion. The blood glucose level before ingestion was stratified into a borderline group (blood glucose level >/= 111 mg/dl) and a normal group (blood glucose level 相似文献   

The effect of oral glucose tolerance testing on changes in arterial stiffness and blood pressure in elderly women with hypertension and relationships between the stage of diabetes and physical fitness levels

[Purpose] The purpose of this study was to assess changes in blood glucose level, blood pressure, and arterial stiffness after a 75 g oral glucose tolerance test (OGTT) in elderly women aged over 65 years with hypertension and either normal glycemic control, impaired fasting glucose tolerance, or diabetes mellitus. We also wished to investigate the relationship between stages of diabetes and physical fitness.[Methods] A total of 24 elderly women with hypertension were assigned to a control group (CON; n=7), impaired fasting glucose group (IFG; n=9), and diabetes mellitus group (DM; n=8). In each group, blood glucose level, brachial ankle pulse wave velocity (PWV), and blood pressure were measured at baseline as well as 60 and 120 minutes after a 75 g OGTT. Physical fitness factors such as hand grip strength, balance test, 4 m gait speed test, chair stand test, short physical performance battery, and 6-minute walking test were subsequently assessed.[Results] In all three groups, blood glucose levels were significantly increased at 60 and 120 minutes after a 75 g OGTT. In the DM group, blood glucose levels were significantly higher before and after a 75 g OGTT than in the CON group. In the CON group, PWV was significantly increased at 60 minutes after a 75 g OGTT; however, there were no changes in other groups after glucose ingestion. In the CON group, systolic and diastolic blood pressures were significantly decreased at 60 and 120 minutes after a 75 g OGTT compared to baseline. However, there was no change in blood pressure after ingestion in the DM group. The IFG group had greater grip strength than the CON group; however, there were no differences in other variables between the groups.[Conclusion] After a 75 g OGTT, elderly women with hypertension and diabetes maintain higher blood glucose levels compared to those with hypertension alone. Unlike elderly women with hypertension alone, those with hypertension and diabetes did not show changes in arterial stiffness and blood pressure after a 75 g OGTT. Therefore, elderly women with hypertension and diabetes may not be able to control their blood vessels following a 75 g OGTT due to impaired vascular endothelial function. Moreover, there was no association between diabetes stage and physical fitness in elderly women with hypertension.     

Role of p-glycoprotein expression in predicting response to neoadjuvant chemotherapy in breast cancer-a prospective clinical study

Background

Lung cancer still remains one of the most commonly occurring solid tumors and even in stage Ia, surgery fails in 30% of patients who develop distant metastases. It is hypothesized that these must have developed from occult circulating tumor cells present at the time of surgery, or before. The aim of the present study was to detect such cells in the peripheral blood and to monitor these cells following surgery.

Methods

30 patients treated for lung cancer with surgery were monitored for circulating epithelial cells (CEC) by taking peripheral blood samples before, 2 weeks and 5 months after surgery and/or radiotherapy (RT) chemotherapy (CT) or combined RT/CT using magnetic bead enrichment and laser scanning cytometry (MAINTRAC^®) for quantification of these cells.

Results

In 86% of the patients CEC were detected before surgery and in 100% at 2 weeks and 5 months after surgery. In the control group, which consisted of 100 normal donors without cancer, 97 % were negative for CEC. A significantly higher number of CEC was found preoperatively in patients with squamous cell carcinoma than in those with adenocarcinoma. In correlation to the extent of parenchymal manipulation 2 weeks after surgery, an increase in numbers of CEC was observed with limited resections (18/21) whereas pneumonectomy led to a decrease (5/8) of CEC, 2 weeks after surgery. The third analysis done 5 months after surgery identified 3 groups of patients. In the group of 5 patients who received neo- or adjuvant chemo/radiotherapy there was evidence that monitoring of CEC can evaluate the effects of therapy. Another group of 7 patients who underwent surgery only showed a decrease of CEC and no signs of relapse. A third group of 11 patients who had surgery only, showed an increase of CEC (4 with an initial decrease after surgery and 7 with continuous increase). In the group with a continuous increase during the following 24 months, 2 early relapses in patients with stage Ia adenocarcinoma were observed. The increase of CEC preceded clinical detection by six months.

Conclusion

We consider, therefore, that patients with adenocarcinoma and a continuous increase of CEC after complete resection for lung cancer are at an increased risk of early relapse.     

Type I (insulin dependent) diabetes: a disease of slow clinical onset?

Type I (insulin dependent) diabetes is usually believed to present acutely and it is assumed that metabolic decompensation is sudden. In a prospective family study, however, 10 of 13 subjects developing the disease showed progressive or intermittent development of hyperglycaemia over many months and the others had non-specific symptoms over a long period. All were first degree relatives of a child with type I diabetes; 10 were siblings (aged 5-24) and three were parents (aged 45-58). All possessed HLA-DR4 or DR3, or both, and all but two had been positive for islet cell antibodies for six to 86 months before diagnosis. Ten had non-specific symptoms for two to 14 months before the onset of thirst and polyuria; one remained asymptomatic even when insulin became necessary. Six subjects had an oral glucose tolerance test before clinical onset, of whom five were diabetic by World Health Organisation criteria four, four, six, seven, and 21 months before insulin was needed. Nine showed random blood glucose concentrations above the 97.5th centile (6.3 mmol/l) six to 34 months (median 12) before diagnosis. Two others had a glucose tolerance test result compatible with diabetes but had not reached the stage of needing insulin. Hyperglycaemia is often of insidious onset in type I diabetes, even in children and young adults. Diagnosis will inevitably be late if considered only when acute symptoms of thirst and polyuria develop.     

Aggravation of ischemia/reperfusion-induced gastric lesions in streptozotocin-diabetic rats

We examined the influence of diabetes on ischemia/reperfusion-induced gastric damage in rats, in relation to the antioxidative system. Animals were injected with streptozotocin (STZ: 70 mg/kg, i.p.) and used after 5 weeks of diabetes with blood glucose levels of >350 mg/dl. Gastric mucosal blood flow (GMBF) was measured before, during and after 20 min of ischemia (1.5 ml bleeding per 100 g body weight from the carotid artery) followed by a 15-min reperfusion in the presence of acid (100 mM HCI). At the end of each experiment, gastric damage was observed macroscopically. GMBF was reduced by ischemia in all groups of rats, followed by a gradual return after reperfusion. Ischemia/reperfusion produced hemorrhagic lesions in normal rat stomachs in the presence of 100 mM HCl. These lesions were significantly aggravated when the animals were pretreated with diethyldithiocarbamate, an inhibitor of superoxide dismutase (SOD). Ischemia/reperfusion-induced damage was also markedly exacerbated in STZ-diabetic rats, but this aggravation was significantly suppressed by pretreatment with exogenous SOD or glutathione (GSH). Diabetic rat stomachs showed significantly less SOD activity as well as GSH content than normal rat stomachs. In addition, the deleterious influence of diabetes on the gastric ulcerogenic response to ischemia/reperfusion was significantly mitigated by decreasing the blood glucose levels by daily insulin treatment. These results suggest that the gastric mucosa of diabetic rats is more vulnerable to ischemia/reperfusion-induced injury, and the mechanism may be partly accounted for by impairment of the antioxidative system associated with a reduced SOD activity and GSH content.