肥胖对非胰岛素依赖型糖尿病患者左心室功能的影响

目的：探讨肥胖对非胰岛素依赖型糖尿病（ＮＩＤＤＭ）患者左心室功能的影响。方法：采用超声心动图检测１８３例非胰岛素依赖型糖尿病患者左心室功能及结构参数。结果：不论血压正常或是合并高血压的非胰岛素依赖型糖尿病患者，随体重指数增大舒张期二尖瓣口血流频谱Ａ峰与Ｅ峰峰值流速比值（ＰＶＡ／ＰＶＥ）、每搏输出量、左心室重量指数均增加，二尖瓣前叶斜率、射血分数、短轴缩短率均降低，以血压正常者变化为著；舒张末期心室间隔厚度与左心室后壁厚度比值（ＩＶＳＴｄ／ＬＶＰＷＴｄ）则无变化。合并高血压的非胰岛素依赖型糖尿病患者较血压正常者有较高的ＰＶＡ／ＰＶＥ、ＩＶＳＴｄ／ＬＶＰＷＴｄ和左心室重量指数，而二尖瓣前叶斜率较低。结论：肥胖可诱发非胰岛素依赖型糖尿病患者左心室收缩功能异常并加重舒张功能损害。     

对上海地区中国汉族人NIDDM中胰升糖素受体基因Gly40Ser突变的研究

目的 明确胰升糖素受体（ＧＣＧ－Ｒ）基因Ｇｌｙ４０Ｓｅｒ突变是否与中国人ＮＩＤＤＭ相关。方法 随机选择上海地区中国汉族人２７６例ＮＩＤＤＭ者,应用ＰＣＲ／ＢｓｔＥⅡ酶解法检测Ｇｌｙ４０Ｓｅｒ突变。结果 本组中国人ＮＩＤＤＭ中未发现一例该突变。结论 该突变可能不是中国人ＮＩＤＤＭ的重要遗传因素。文献报道白种人中ＧＣＧ－Ｒ基因Ｇｌｙ４０Ｓｅｒ与ＮＩＤＤＭ相关,本研究结果提示此种相关有明显的种族异质性。     

老年脂肪肝的病因分析

目的研究老年脂肪肝的主要病因,探求防治措施。方法比较分析１８２例老年脂肪肝与对照组的研究资料。结果老年脂肪肝组的体重指数（ＢＭＩ）、血清甘油三酯（ＴＧ）、血糖（ＧＬＵ）水平和异常率与对照组比较差异非常显著（Ｐ＜０００１,Ｐ＜００１）。结论肥胖症、高甘油三酯血症、非胰岛素依赖型糖尿病（ＮＩＤＤＭ）是老年脂肪肝的主要病因,减肥、有效地控制高甘油三酯血症和糖尿病,是防治老年脂肪肝的重要措施。     

Triple Oral Antidiabetic Therapy

Our objective was to determine the efficacy of adding acarbose to the combination of metformin and a sulfonylurea in the treatment of type II diabetes mellitus. Acarbose was added to the treatment regimen of 11 type II diabetic patients who were not adequately controlled on the combination of a sulfonylurea and metformin. Glycosylated hemoglobin before and after the addition of acarbose was compared to assess the efficacy of this additional therapy. One patient did not tolerate acarbose therapy. Of the remaining ten patients, the mean improvement in glycosylated hemoglobin with the addition of acarbose was 1.4 percentage points, p = 0.01. Eight patients had improvements in glycosylated hemoglobin; mean improvement, 2.0 percentage points. Two patients’ glycohemoglobin values worsened. Thus, the addition of acarbose to the treatment regimen of type II diabetic patients presently on a combination of a sulfonylurea and metformin improves glycemic control.     

Insulin treatment and cardiovascular disease; friend or foe? A point of view

BACKGROUND: Several observational studies have shown that higher insulin levels are associated with an increased risk of cardiovascular disease. If higher endogenous insulin levels are causally related to cardiovascular disease, one might expect an increased risk of cardiovascular disease in patients treated with insulin, as this results in high circulating insulin levels. Such risk elevation might counteract the benefits of tight glucose control. Our objective was to explore the relationship between insulin therapy and cardiovascular disease in Type 1 and Type 2 diabetes mellitus using information from available literature. SUMMARY OF COMMENT: Several experimental studies in animals and humans support the presence of a harmful effect of insulin on the vascular endothelium. In prospective follow-up studies increased insulin dosage was associated with increased risks of cardiovascular disease, although confounding by indication could not be excluded. Randomized controlled trials in diabetic patients, comparing conventional with intensive glucose-lowering treatment, although showing a reduction in microvascular disease, showed no significant difference in the incidence of cardiovascular disease. The results with respect to exposure to insulin are, however, difficult to interpret due to insufficient information on exposure to insulin levels as well as confounding by glycaemic control and body mass index. In addition, these studies were not designed to address the question whether higher insulin use relates to increased cardiovascular risk. CONCLUSION: Published research provides conflicting evidence as to whether exposure to high levels of exogenous insulin in diabetes mellitus affects the risk of cardiovascular disease. The currently available studies have a number of serious methodological restraints that limit accurate interpretation and conclusions in this area.     

Initial Evaluation of a 290-μm Diameter Subcutaneous Glucose Sensor: Glucose Monitoring with a Biocompatible, Flexible-Wire, Enzyme-Based Amperometric Microsensor in Diabetic and Nondiabetic Humans

Results of the initial clinical evaluation in 20 human subjects of a subcutaneously implanted microsensor-based amperometrically glycemia-monitoring system, carried out between April 1994 and June 1995, are reported. The system was based on the electrical connection (“wiring”) of the reaction centers of glucose oxidase to a gold electrode and on elimination of the chemicals that interfere with glucose monitoring through their horseradish peroxidase-catalyzed oxidation by internally generated hydrogen peroxide. The sensor was finer than a 29-gauge needle and had no leachable components. Because of its high selectivity for glucose, the sensor output was virtually nil at zero glucose level. This enables prompt “one-point” in vivo calibration of the sensor with a single blood glucose sample. Microsensors were subcutaneously implanted in ten nondiabetic and ten insulin-dependent diabetes mellitus (IDDM) volunteers. All subjects underwent standard meal tests and intravenous glucose-tolerance tests (IVGTT) in addition to hourly plasma glucose measurements. The sensor signals were continuously recorded, and the glucose concentration estimates were derived by calibrating the sensor using a single blood sample (one-point calibration). Regression analysis revealed that the sensor-estimated glucose concentrations were linearly related to the plasma glucose concentrations (r² = 0.75) over a wide glucose concentration range (2–28 mmol/L) (sensor estimate = plasma * 0.96 + 0.26 mmol/L). The difference between the estimated and actual glucose concentration was −0.13 ± 0.23 mmol/L [mean ± 95% confidence interval (CI), n = 546], and 95% of the estimates fell in clinically acceptable zones of the Clarke error grid. The sensing delay time was 10.4 ± 2.3 min as measured by the IVGTT. The subjects reported no discomfort associated with wearing the sensors.     

Microneurographically Determined Muscle Sympathetic Nerve Activity Levels Are Reproducible in Insulin-Dependent Diabetes Mellitus

Our objective was to determine whether microneurographically determined muscle sympathetic nerve activity (MSNA) levels are equally reproducible in control and insulin-dependent diabetes mellitus (IDDM) subjects. We used a retrospective review of MSNA levels in 14 IDDM and 16 control subjects who had at least two microneurographic studies in the last 8 years in our laboratory. Results showed mean MSNA levels were lower in IDDM (9.2 ± 1.2 bursts/min) than in control subjects (16.8 ± 1.7 bursts/min) (p < 0.002) but mean within individual MSNA coeffients (IDDM: 47 ± 8%; controls 30 ± 5%) and ranges of variation (IDDM: 6.6 ± 1.9; controls: 7.5 ± 1.9 bursts/min) did not differ between IDDM and control subjects. Thus, microneurographically determined MSNA levels are equally reproducible in IDDM and controls subjects. These results confirm and substantiate our previous findings of diminished MSNA in IDDM subjects.     

B-cell function and blood glucose control in insulin dependent diabetics within the first month of insulin treatment

Summary Seventeen insulin dependent diabetics were studied after two to four weeks of insulin treatment in a situation approximating to their normal daily life. Some endogenous insulin secretion, assessed by plasma C-peptide determinations, was present in all. Plasma C-peptide concentration was positively correlated with the blood glucose concentration and increased after breakfast, lunch and dinner (p<0.01); both peak values and relative increases were lower than those observed in normal subjects (p<0.01). The highest insulin secretory capacity was found in subjects with the least unstable blood glucose concentration (r=0.57, p <0.03), and these patients required the smallest insulin doses (r=0.54, P<0.04). These findings demonstrate the metabolic importance of a preserved B-cell function.     

2型糖尿病血小板膜糖蛋白CD62p、CD63的变化及影响因素

目的　探讨 2型糖尿病患者血小板膜糖蛋白CD6 2p、CD6 3的变化及临床价值。方法　用流式细胞术测定64例 2型糖尿病患者 (有微血管病变者 3 1例 ,无微血管病病变者 3 3例 )及 3 0例健康人血小板膜糖蛋白CD6 2 p、CD6 3,并对部分患者作治疗前后的动态观察。结果　血小板膜糖蛋白CD6 2 p、CD6 3的表达在 2型糖尿病患者中明显高于正常对照 ,伴微血管病变组明显高于无微血管病变组。部分患者在血糖控制后并坚持服用阿斯匹林 6个月 ,所有指标与治疗前比较差异无显著性。多元逐步线性回归分析表明在 2型糖尿病病人中 ,CD6 2 p、CD6 3水平与胰岛素敏感指数、年龄及病程有关。结论　血小板膜糖蛋白CD6 2p、CD6 3测定对判断 2型糖尿病病人血小板活化和微血管病变的早期诊断、病情分析有重要的临床价值 ,其水平变化与胰岛素敏感指数、年龄及病程有关     

非胰岛素依赖型糖尿病肾组织中凝集素受体含量与分布的研究

应用组织化学及免疫组织化学染色对１０例非胰岛素依赖型糖尿病（ＮＩＤＤＭ）和１０例对照组的尸检肾脏标本的病理形态、凝集素受体含量和分布进行了研究。结果：（１）糖尿病肾小球基底膜（ＧＢＭ）和系膜基质呈弥散和不均匀性增厚。３０％的病例可见肾小球结节性硬化，７０％的病例有肾小球纤维化，在肾小管周围有透明变性的物质沉积。（２）对照组的ＧＢＭ上有蓖麻凝集素（ＲＣＡ）和花生凝集素（ＰＮＡ）受体，肾小管上皮细胞的腔缘对麦胚凝集素（ＷＧＡ）和ＲＣＡ有特异的亲和性。绝大多数ＮＩＤＤＭ的ＧＢＭ无ＲＣＡ表达，对ＷＧＡ的亲和性却明显增加，与对照组比较均有显著性差异。糖尿病ＧＢＭ中ＢＤ半乳糖含量减少，而Ｎ乙酰氨基葡萄糖却异常增多，其糖基的变化均可使ＧＢＭ维持电荷屏障的功能减低，通透性发生改变。两组双花扁豆凝集素（ＤＢＡ）和大豆凝集素（ＳＢＡ）在肾小管的表达无明显差异；荆豆凝集素（ＵＥＡ）和刀豆凝集素（ＣｏｎＡ）在肾组织中均不着色。提示ＮＩＤＤＭ肾小球基底膜中凝集素受体的异常表达，可能是引起糖尿病性肾病的原因之一。     

Prevalence of Hypertension in Patients with Type II Diabetes in Referral versus Primary Care Clinics

We compared the prevalence of hypertension in patients with non–insulin-dependent diabetes mellitus (NIDDM) in referral and primary care practices using definitions of The Fifth Report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure (JNC-V), while controlling for other risk factors such as hypertension, obesity, smoking, and age. Patients (n = 1443) were enrolled consecutively from a large referral practice at the Jackson Diabetes Center and four primary care clinics in the vicinity. Blood pressures were measured at three clinic visits after a 5-min rest in a sitting position using a standard clinical sphygmomanometer. Charts were reviewed to determine diabetes duration, insulin usage, height, weight, smoking history, use of antihypertensive and oral hypoglycemic medications, socioeconomic status, and race. Patients were classified as hypertensive based on JNC-V definitions or if they were on antihypertensive medication. Hypertension was termed uncontrolled if blood pressure was JNC-V Stage 2 or higher while on antihypertensive medication.

Seventy-eight percent of referral clinic and 55% of primary care clinic patients had either JNC-V State 1 or higher hypertension or were on antihypertensive medication. Actual blood pressures indicated that more patients had JNC-V Stage 1 (mild) or higher hypertension in referral compared to primary care clinics (62% versus 48% p = 0.01) but fewer had JNC-V Stage 2 or higher (moderate-severe) hypertension (12% versus 19% p = 0.002). Patients seen in the referral clinic were significantly more likely to have greater age, greater duration of diabetes, higher insulin dosage, longer smoking history, antihypertensive medication, and live outside the metropolitan area. By logistic regression, the odds of hypertension were significantly increased with age (OR 1.51/decade), BMI greater than 27 (OR 2.17), diabetes duration (OR 1.04/year), and insulin dosage (OR 1.74/U/kg). Current smoking and attending a referral clinic were not significantly related. The odds of moderate-severe hypertension were significantly increased with age (OR 1.23/decade), decreased by attending a referral clinic (OR 0.45), and not significantly related to other confounders in the model.

The prevalence of hypertension among patients with NIDDM was higher in referral than primary care clinics. The higher prevalence in the referral practice can be accounted for by the greater severity of associated risk factors in the referral practice patients; however, most patients will be diagnosed and treated for hypertension prior to referral. More patients in the referral practice were on hypertensive medication, which lowered the stage or severity of hypertension but still not to the normal range. The results suggest that the primary detection of hypertension in patients with type II diabetes resides with the primary care physician. Management of hypertension will require both a delineation and acceptance of responsibilities between the primary care physician and diabetes specialists.     

胰岛素抵抗、胰岛素分泌功能对Ⅱ型糖尿病发生的影响

目的探讨中国非糖尿病人群中胰岛素抵抗、胰岛素分泌功能对糖尿病发生的影响。方法以Ｈｏｍａ模型的胰岛素抵抗指数（ＩＲ）＝ＦＩＮＳ／２２５ｅ－ｌｎＦＰＧ（ＦＩＮＳ为空腹胰岛素，ＦＰＧ为空腹血糖）及β细胞功能指数（ＨＢＣＩ）＝ＦＩＮＳ×２０／（ＦＰＧ－３５），对４０９例非糖尿病者６年随访资料进行糖尿病发病危险因素的比例风险模型分析，再以胰岛素敏感性指数（ＩＡＩ）＝１／（ＦＰＧ×ＦＩＮＳ）、胰岛素分泌功能指数（ＩＳ）＝ＦＩＮＳ／ＦＰＧ这对更简单的指数进行同样分析，并与前者比较。结果以Ｈｏｍａ模型的ＩＲ、ＨＢＣＩ分析显示，排除口服葡萄糖耐量试验２小时血糖、体重指数因素影响后，ＩＲ与糖尿病正相关（Ｐ＜００５），ＨＢＣＩ与糖尿病负相关（Ｐ＜０．０１），生活方式干预有利于减少糖尿病发病危险。与以ＩＡＩ＝１／（ＦＩＮＳ×ＦＰＧ）、ＩＳ＝ＦＩＮＳ／ＦＰＧ分析结果相似。结论（１）胰岛素抵抗及胰岛素分泌功能差是Ⅱ型糖尿病发病危险因素；（２）仅涉及空腹血糖及空腹胰岛素的Ｈｏｍａ模型在流行病研究中可用于评价胰岛素抵抗及β细胞功能，ＩＡＩ＝１／（ＦＰＧ×ＦＩＮＳ）、ＩＳ＝ＦＩＮＳ／ＦＰＧ可在分析中代替Ｈｏｍａ模型     

The effect of Ramadan fasting on glycaemic control in insulin dependent diabetic patients: A literature review

Background

Ramadan fasting is one of the five pillars of Islam. People with diabetes are exempted from fasting according to Islamic rules. However, many people with diabetes wish to fast. Physicians are asked frequently by their patients about their ability to fast and the possible impact of fasting on their glycaemic control. Studies about the effect of Ramadan on people with insulin-treated diabetes are scarce. This review aims to provide clinicians with the best recommendations for their patients with insulin-treated diabetes who wish to fast.

The effects of increasing doses of enalapril on insulin sensitivity in normotensive non-insulin dependent diabetic subjects

Background: There are conflicting reports about the effects of ACE inhibitors (ACEI) on insulin sensitivity and glycaemic control. Most studies have used a standard high dose of an ACEI but there have been no studies reported to establish whether any changes in glycaemic control or insulin sensitivity associated with ACEI are dose-related. Aim: To examine the effect of increasing doses of enalapril on insulin sensitivity in normotensive non-insulin dependent diabetic subjects. Methods: The effects of increasing doses of enalapril on insulin sensitivity in ten normotensive non-insulin dependent diabetic subjects were measured, using the hyperinsulinaemic isoglycaemic clamp technique. Following a baseline study, enalapril was commenced at 5 mg daily and increased to 10 mg daily then 20 mg daily at 14 day intervals. Repeat studies were undertaken after 14 days at each dosage. Results: There was a significant dose-related reduction of systolic blood pressure with enalapril. In contrast enalapril at 5-20 mg daily produced no significant changes in insulin mediated glucose uptake (M-value) or insulin sensitivity index (ISI). Conclusions: These findings indicate that in this insulin resistant population of normotensive non-insulin dependent diabetics, angiotensin converting enzyme inhibition with enalapril has no significant effect on insulin mediated glucose uptake.     

Hyperproinsulinaemia and risk of Type 2 diabetes mellitus in women.

AIMS: Our objective was to examine prospectively the associations between fasting plasma proinsulin and the proinsulin/insulin ratio and the incidence of Type 2 diabetes in women. SUBJECTS AND METHODS: We designed a nested case-control study within the Nurses' Health Study, a cohort of 121,700 US women aged 30-55 years at study inception in 1976. Fasting plasma proinsulin, specific insulin and C-peptide levels were determined in 183 women with a new diagnosis of diabetes made after blood sampling between 1989 and 1990, and 369 control subjects without diabetes. RESULTS: After adjustment for age, body mass index, family history of diabetes and other potential confounders, including HbA1c, the odds ratios for diabetes associated with increasing quartiles of proinsulin were 1.00, 0.85, 2.49 and 5.73 (P for trend: < 0.001). Proinsulin remained significantly associated with diabetes risk after adjusting for C-peptide and specific insulin (multivariate odds ratios for quartiles: 1.00, 0.78, 1.94, 3.69; P for trend = 0.001). In addition, the proinsulin/insulin ratio was significantly associated with diabetes risk, controlling in multivariate analysis for C-peptide (odds ratios for extreme quartiles: 2.48; 95% CI: 1.14-5.41; P for trend = 0.005). CONCLUSIONS: These data suggest that proinsulin and the proinsulin/insulin ratio are strong independent predictors of diabetes risk, after adjustment for obesity and other potential confounders.     

Serum lipase,isoamylase and pancreatic function test (PFT) in juvenile-onset insulin-dependent diabetes mellitus

Summary Significantly decreased activity of pancreatic isoamylase in serum was found in a group of 51 juvenile-onset insulin-dependent diabetics as compared to healthy subjects (p<0.005). No significant changes were observed for urinary p-aminobenzoic acid excretion in 20 of the juvenile-onset diabetics in whom the NBT-PABA test was performed, even though 25% of the values were below the normal limit. A highly significant decrease of serum lipase activity was found in juvenile-onset diabetics as compared to controls (p<0.001). No significant correlation was found in juvenile-onset diabetics between serum pancreatic isoamylase and lipase or marker of chymotrypsin activity expressed as the amount of p-aminobenzoic acid excreted into urine. The NBT-PABA test appears to be of small importance in the evaluation of changes of the exocrine pancreas in insulin-dependent diabetes mellitus. However, simultaneous evaluation of serum pancreatic isoamylase and lipase activities justified the suspicion of pancreatic damage in 50% of the patients tested.     

核素肾动态显像对老年非胰岛素依赖型糖尿病患者肾功能的研究

目的旨在评价非胰岛素依赖型糖尿病（ＮＩＤＤＭ）老年患者糖尿病肾病（ＤＮ）的进程，为临床治疗和判断预后提供依据。方法以９９ｍＴｃ－ＤＴＰＡ为示踪剂进行肾动态显像，同时获得肾小球滤过率（ＧＦＲ）、肾功能曲线和肾动态显像。结果本组患者ＧＦＲ均降低，病程≤１０年（６５．３±１３．１ｍｌ／ｍｉｎ）和病程＞１０年（５４．２±１５．７ｍｌ／ｍｉｎ）较对照组（９０．４±１６．６ｍｌ／ｍｉｎ）明显降低（Ｐ＜０．０１）；肾功能曲线峰时，病程≤１０年（左右肾分别为４．４±１．５及４．４±１．４分）和病程＞１０年（４．５±１．８及４．６±１．７分）较对照组（均为３．６±０．９分）明显后延（Ｐ＜０．０１），１０和２０分钟残存率均增高，后者仅病程＞１０年（左右肾分别为５４．２％±１４．１％及５３．９％±１４．２％）者较对照组（４８．６％±８．３％及４８．２％±９．３％）明显增高（Ｐ＜０．０５）。结论本组糖尿病患者的肾脏滤过和排泌功能均受损，其程度随ＮＩＤＤＭ病程的延长而加重，提示病程已进入ＤＮⅡ～Ⅳ期。     

BENEFICIAL EFFECTS OF FENOLDOPAM TREATMENT ON RENAL FUNCTION IN STREPTOZOTOCIN-INDUCED DIABETIC RATS

We have studied the effect of chronic treatment with dopamine D1 receptor agonist fenoldopam (1?mg/kg, i.p. daily for 6 weeks) on renal function and metabolic parameters in streptozotocin (STZ)-diabetic rats. Diabetes was induced by a single tail vein injection of STZ (45?mg/kg). STZ produced severe hyperglycemia, hypoinsulinemia, hypercholesterolemia, hypertriglyceridemia, hypertension and bradycardia. Fenoldopam treatment significantly reduced fasting but not fed blood glucose levels and lowered the blood pressure in diabetic animals. Significant change was not observed in insulin, cholesterol, triglyceride levels. Diabetic animals showed increase in AUC_glucose and decrease in AUC_insulin during oral glucose tolerance test. Fenoldopam treatment did not significantly change these values in diabetic animals. STZ produced increase in serum urea, creatinine and blood urea nitrogen. Diuresis and urinary sodium retention was observed in diabetic animals. Renal hypertrophy was observed as seen from increased kidney weight/body weight ratio and increased total RNA content as well as decreased total DNA content. Fenoldopam treatment significantly lowered serum urea, creatinine and blood urea nitrogen. Urinary sodium retention was significantly reduced and renal hypertrophy was prevented with fenoldopam treatment as seen from the improved kidney weight/body weight ratio. Fenoldopam treatment significantly prevented reduction in total DNA content and increase in total RNA content further substantiating reduced renal hypertrophy. Our data suggest that STZ induced diabetes is associated with renal dysfunctions and fenoldopam treatment could be beneficial in a condition where diabetes mellitus co-exists with hypertension and compromised renal function.     

老年2型糖尿病患者微量白蛋白尿与胰岛素抵抗的关系

目的了解老年２型糖尿病患者的微量白蛋白尿（ＭＡＵ）与胰岛素抵抗的关系。方法对血压正常的３０例老年２型糖尿病合并ＭＡＵ患者与２６例未合并ＭＡＵ患者的空腹血糖、胰岛素、胰岛素敏感性指数（ＩＳＩ）和血脂等进行比较分析,并对所有患者的尿白蛋白排泄率（ＵＡＥＲ）与有关因素进行多元回归分析。结果２型糖尿病合并ＭＡＵ组ＩＳＩ（－４．９９±０．４８）显著低于未合并ＭＡＵ组（－４．７６±０．４８,Ｐ＜０．０５）,而且ＩＳＩ与ＵＡＥＲ呈独立相关〔标准偏回归系数（β）＝－０．３９７,Ｐ＜０．０１〕。结论在血压正常的老年２型糖尿病患者中,胰岛素抵抗是ＭＡＵ的独立危险因素。