Anti-adrenal medullary antibodies in IDDM subjects and subjects at high risk of developing IDDM

Previous reports have noted the presence of anti-adrenomedullary antibodies in subjects with insulin-dependent diabetes mellitus (IDDM). We initiated a study to evaluate the presence of complement-fixing anti-adrenomedullary antibodies (CF-ADM) in the following subjects: group 1 (age 4-60 yr), anti-islet cell antibody-positive (ICA+) subjects at high risk of developing diabetes, in which 9 (32%) of 28 were positive for CF-ADM; group 2 (age 6-41 yr), anti-ICA negative (ICA-) subjects at high risk of developing diabetes, in which 0 (0%) of 15 were positive for CF-ADM; group 3 (age 1-58 yr), ICA+ diabetic subjects, in which 7 (30%) of 23 were positive for CF-ADM; group 4 (age 5-68 yr), ICA- diabetic subjects, in which 1 (4%) of 24 was positive for CF-ADM; group 5 (age 20-56 yr), volunteer blood bank donor controls, in which 2 (6%) of 32 were positive for CF-ADM; and group 6, known healthy controls, in which 0 (0%) of 14 were positive for CF-ADM. CF-ADM were increased in group 1 compared with group 2 (P less than .02) and both control groups (P less than .02). CF-ADM were increased in group 3 compared with group 4 (P less than .03) and both control groups (P less than .03 vs. group 5, P less than .05 vs. group 6). Presence of CF-ADM was associated with presence of ICA in group 1 (P less than .02) and group 3 (P less than .03).(ABSTRACT TRUNCATED AT 250 WORDS)     

Nicotinamide treatment in subjects at high risk of developing IDDM improves insulin secretion.

Nicotinamide (NCT) has been shown to be effective in preventing the onset of type 1 diabetes mellitus (IDDM) in mice with non-obese diabetic (NOD) and beta cell damage, mediated by the diabetogenic agents including streptozotocin. NCT therapy in man has been shown to have a beneficial effect on the remission phase of IDDM, and its use is safe. In this open pilot trial we therefore studied the effect of oral NCT administration on insulin secretion rate and islet-cell antibody (ICA) titres in IDDM high risk subjects. NCT (25 mg/10 kg bw) was administered in 6/13 high risk patients identified by a family screening programme. Those subjects tested after eight months without treatment showed a decreasing secretion in comparison to onset baseline (56,1 +/- 37.8 versus 35,5 +/- 12.2), whereas the treated subjects showed an increasing insulin secretion after treatment (26 +/- 10 versus 50.2 +/- 26.6), in spite of ICA persistence. Statistical analysis shows an increased insulin secretion in the treated group versus the untreated group (chi 2 = 3.899, P = 0.048). No side-effects were observed. We conclude that NCT may repair beta-cell function in high risk subjects too if damage is not too severe; furthermore, the effect seems not to be mediated by an immune mechanism.     

Beat-to-beat blood pressure response in asymptomatic IDDM subjects

Nine insulin-dependent diabetic (IDDM) patients (aged 25-37 yr) with no symptoms of autonomic neuropathy and 15 healthy control subjects (aged 26-39 yr) were studied at rest and during tests of Valsalva maneuver, deep breathing, cold pressor, and postural change from sitting to standing. Continuous (beat-to-beat) measures were taken of heart rate, systolic blood pressure, diastolic blood pressure, and skin conductance. The diabetic patients were differentiated from the control group by the following: less variability in diastolic blood pressure during deep breathing, failure to exhibit diastolic blood pressure decreases during recovery from a cold pressor stimulus, a flatter blood pressure response pattern when changing from sitting to standing, and a smaller standing ratio (maximum/minimum) for R-R interval. Among the patients, age was negatively correlated with systolic and diastolic standing ratios and diastolic blood pressure variability during deep breathing. By use of the tracking cuff, a method of continuously recording blood pressure noninvasively, we have been able to assess subtle blood pressure changes, thereby revealing signs of sympathetic dysfunction in a group of relatively young diabetic patients with no symptoms of neuropathy. The tracking-cuff method of recording blood pressure has potential in further research on autonomic functioning in diabetic patients.     

Assessment of AlbuSure and its usefulness in identifying IDDM subjects at increased risk for developing clinical diabetic nephropathy

This study, which included 154 participants in a 10-yr follow-up study of diabetes complications, was conducted to evaluate AlbuSure (a qualitative test designed to detect urinary albumin concentrations greater than 0.03 g/L) for its ability to discriminate between albumin concentrations above and below the manufacturer's concentration threshold and to identify individuals at increased risk for developing diabetic nephropathy (i.e., those with albumin excretion rate [AER] greater than 0.0288 g/24 h). The reproducibility of AlbuSure results was also evaluated. The results of these evaluations were examined by three different types of urine collections (24 h, overnight, and timed postclinic) and overall. AlbuSure's validity was examined by comparing its results to immunonephelometrically measured concentrations and AER. When compared to albumin concentration, AlbuSure had an overall sensitivity of 81.8%, specificity of 94.8%, and positive predictive value of 90.6%. AlbuSure's sensitivity was lower (71.4%) when compared with AER; however, this was higher than the sensitivity achieved by dipsticks against AER (50.7%). On testing urine samples stored for 3 days at 4 degrees C, AlbuSure results were 100% reproducible after 1 day and had an overall reproducibility of 92% after 3 days. When urine was retested after 3 and 15 mo of storage at -70 degrees C, AlbuSure was greater than or equal to 90% reproducible, with some of the differing results attributable to corresponding changes in albumin concentration. The overnight sample appeared to be the sample of choice for testing with AlbuSure in that it showed excellent reproducibility and the highest sensitivity (compared to both albumin concentration and AER).     

Grey matter changes over time in high risk subjects developing schizophrenia

Schizophrenia affects approximately 1% of the population and is associated with reductions in brain volume, but when these are first evident is unknown. Magnetic resonance imaging (MRI) has demonstrated abnormalities of brain structure, particularly of the temporal lobes, in schizophrenia. A study of brain structure in individuals destined to develop schizophrenia, before they do so, is crucial to understanding the illness. We used Voxel Based Morphometry (VBM) to map changes in Grey Matter Density (GMD) in 65 young adults at high risk of schizophrenia, for familial reasons, and 19 healthy young adults, over a period of approximately 2 years. All subjects were anti-psychotic naive at both scans. No increases in GMD were found in any of the groups. Within the high-risk group significant declines in GMD were found in the temporal lobes, the right frontal lobe and right parietal lobe. In the control group a decline was found in the right gyrus rectus. No significant differences over time were found between any of the groups. Those individuals at high risk who had transient or isolated psychotic symptoms showed a different spatial pattern of reductions in GMD than those who did not in within group comparisons. In addition, those individuals at high risk who later developed schizophrenia also showed a different spatial pattern of reductions in GMD in the left temporal lobe and right cerebellum, from 2 to 3 years before they were diagnosed. These particular reductions may therefore be able to predict the later onset of schizophrenia.     

高原高血压24h动态血压研究

目的观察高原高血压24h动态血压变化.方法应用美国Spacelabs90207动态血压监测仪观察了60例高原高血压24h动态血压并与年龄、性别相匹配的60例高血压病(EH)患者进行比较.结果高原高血压患者24h血压节律与EH基本相同,两组患者夜间血压水平均明显下降,但高原高血压以DBP增高为著;高原高血压患者与EH患者24h血压曲线白昼(600～2200)及夜间(2200～600)曲线均呈重叠、交叉状态.结论凡移居高原前血压正常,移居高原后血压持续增高,能除外原发和继发性高血压,24h动态血压监测显示血压波动曲线呈长柄杓型,且以DBP增高为著,提示为高原高血压.返回平原后血压能恢复正常.     

三种不同透析模式在血液透析高危患者中对血压的影响及比较

目的观察比较常规、低温及低温可调钠三种透析模式在血液透析高危患者中对血压的影响。方法选择上海交通大学附属上海市第一人民医院松江分院肾内科血液透析患者20例,均为高龄、糖尿病肾病及心功能不全伴有终末期肾病患者,随机分别采用常温常规透析、低温常规透析、低温加可调钠透析三种透析模式,每例患者每种模式观察10次,比较透析时出现低血压及低血压症状出现的例次数。结果常温常规组（A组）,低温常规组（B组）和低温可调钠组（C组）出现低血压的发生率分别为20.5%,15.5%及7%,C组与A组比较,差异有显著性（P〈0.01）。结论低温可调钠透析可有效地降低血液透析高危患者透析中出现低血压的发生率,提高血液透析的耐受性。     

Immunorestorative properties of isoprinosine in the treatment of patients at high risk of developing ARC or AIDS

We have evaluated the immunomodulatory effects of isoprinosine in a double blind randomized clinical study on 63 immunosuppressed male homosexuals with persistent generalized lymphadenopathy (PGL) or ARC. The subjects received either placebo or isoprinosine at 1 or 3 g/day for 28 days. All subjects were monitored for performance for a one year period. In the 3 g/day treatment group clinical improvement was reported by 52% of the patients in contrast to 15% in the placebo group. Patients receiving 3 g/day isoprinosine showed significant increase in NK cells, a major subset of which bears the Leu 7 surface antigen, and in NK cell function as early as at the termination of treatment. This normalized NK cell property was still evident 5 months after cessation of therapy. Total T lymphocytes and T helper cells also increased in this group and a concomitant reduction was observed in activated T lymphocytes (HLA-DR+). As a direct result of the therapy an increase was found in the Th regulatory (Leu 3+ Leu 8+) cell population resulting in normalization of Th inducer/Th regulatory cell ratio. A concomitant reduction to normal range occurred in Ts effector (Leu 2+ Leu 8-) and functionally activated Ts (Leu 2+ HLA-DR+) cell populations. The kinetics of these effects suggest that isoprinosine stimulates the production of precursor lymphocytes and initiates a process of cell differentiation capable of producing long-term restoration of host immunity.     

Changes in cerebral oxygenation and haemodynamics during postural blood pressure changes in patients with autonomic failure

Patients with autonomic failure suffer severe postural hypotension that may be associated with symptoms of cerebral hypoperfusion. This study utilized near-infrared spectroscopy (NIRS) to measure changes in cerebral oxygenation and haemodynamics during the head-up tilt table test in 18 patients with autonomic failure and 10 healthy age-matched volunteers. Heart rate, blood pressure (MAP), oxygen saturation, cerebral tissue oxygen index (TOI) and total cerebral haemoglobin concentration [HbT] were measured continuously. In patients with autonomic failure there was a mean (SD) reduction in MAP of 46.7 (26.5) mmHg (p < 0.005) associated with a reduction in TOI of 8.6 (6.2)% (p < 0.005) during the head-up tilt table test. In healthy volunteers mean (SD) MAP rose by 12.3 (8.0) mmHg (p < 0.005) and TOI fell by 2.6 (3.2)% (p < 0.05). There was a mean (SD) reduction in [HbT] of 3.09 (2.82) micromol l(-1) (p < 0.005) in patients, equivalent to a decrease in cerebral blood volume of 0.2 (0.18) ml/100 g. There were no changes in [HbT] in the healthy volunteers. Postural hypotension in patients with autonomic failure is associated with a substantial decrease in absolute cerebral oxygenation measured by NIRS and this might reflect a critical reduction in cerebral oxygen delivery.     

Arterial blood pressure related to degree of albuminuria and low-molecular-weight proteinuria in IDDM

Urinary excretion of albumin and retinol-binding protein (a marker of tubular proteinuria that results from impaired proximal tubular reabsorption of low-molecular-weight proteins) was determined in 110 insulin-dependent diabetic (IDDM) subjects. A statistically significant correlation between the urinary excretion of both proteins, in particular the retinol-binding protein, and the height of arterial blood pressure (systolic and diastolic) was observed. Correlation was weak, i.e., factors other than incipient nephropathy could be of greater importance for the development of arterial hypertension in diabetes.     

Endogenous vasopressin affects postural control of blood pressure in man

1. Six healthy volunteers received intravenous infusions of isotonic (0.9% NaCl) and hypertonic (3% NaCl) saline on separate days. There were no significant changes in blood pressure or forearm blood flow, despite an increase in plasma arginine vasopressin (AVP) during hypertonic saline. 2. Immediately and 10 min after passive tilting to 50 degrees, mean forearm blood flow fell by 17.1 and 14.3% compared with the values in the supine position during isotonic saline and by 40.3 and 43.3% during hypertonic saline. Forearm vascular resistance rose by 23.6 and 17.8% with isotonic saline and by 80.2 and 88.2% with hypertonic saline for the two readings in the tilted compared with the supine position. 3. Tilting was associated with a 14.9 and 12.1% rise in diastolic blood pressure immediately and 10 min after assuming this position during hypertonic saline, and a rise of 6.4% in mean arterial pressure. 4. The results from this study are similar to those obtained previously, when small amounts of AVP were infused. They provide further evidence that AVP may have a physiological role in the postural regulation of blood pressure.     

Fibrinolytic system during long-distance running in IDDM patients and in healthy subjects.

OBJECTIVE--Endurance exercise has been advocated in diabetes mellitus to improve both metabolic control and prevent atherosclerotic complications. The response of the fibrinolytic system during prolonged exercise has not been studied in diabetes. RESEARCH DESIGN AND METHODS--In seven male marathon runners with IDDM and eight healthy nondiabetic male control subjects, matched for age and degree of training, we studied fibrinolytic and coagulation parameters during a 3-h 32-km outdoor running session. Measurements included t-PA, u-PA, PAI-1, PAP (as a measure of in vivo activation of fibrinolysis), FbDPs, FGN, vWF, and VIII:C. RESULTS--In both IDDM and control subjects, levels of t-PA, u-PA, PAP, vWF, and VIII:C continued to rise throughout the exercise, whereas PAI-1 showed a similar decline in both groups. FbDP rose slightly in both groups, and FGN remained unchanged. t-PA levels during exercise correlated closely with exercise intensity. These findings indicate that continued stimulation by exercise does not deplete endothelial PA stores. Differences between IDDM and control subjects were seen only for t-PA, vWF, and u-PA. The AUC during exercise (AUC0.5-3.0) of t-PA in IDDM was insignificantly lower than in control subjects (53 +/- 19 vs. 67 +/- 31 ng.ml-1.h), but the ratio of t-PA to exercise intensity was lower in IDDM (0.24 +/- 0.11 vs. 0.31 +/- 0.13, P less than 0.05). The AUC0.5-3.0 of vWF was lower in IDDM than in control subjects (569 +/- 268 vs. 880 +/- 265%.h, P less than 0.05). The AUC0.5-3.0 of u-PA was higher in IDDM than in control subjects (15.1 +/- 3.5 vs. 11.2 +/- 1.8 ng.ml-1.h, P less than 0.05). CONCLUSIONS--Despite a defect in the exercise-induced endothelial release of vWF and t-PA, the overall potential to activate fibrinolysis is intact in IDDM, possibly by enhancement of u-PA after exercise. Our data suggest that in IDDM, as in nondiabetic subjects, long-distance running may slow the progression of atherosclerosis by stimulating fibrinolysis.     

Digital blood pressure in normal subjects and patients with peripheral arterial disease.

Systolic toe blood pressure was measured in 10 normal subjects and 17 patients with peripheral arterial disease during a warming and a cooling period, in which the skin temperature on the first toe was changed from 33 degrees C to 24 degrees C. In normal subjects systolic toe blood pressure increased from an average of 110 mm Hg to 120 mm Hg during cooling (P less than 0.01), while the systolic arm blood pressure was unchanged during the study (125 mm Hg). Among the patients systolic toe blood pressure increased from an average of 56 mm Hg to an average of 70 mm Hg (P less than 0.01), while arm blood pressure increased from an average of 167/79 mm Hg during warming to 175/83 mm Hg during the cooling period. It is emphazised that despite the small, but significant, increase in digital blood pressure during the cooling period, changes in distal temperature will only have a small influence on the digital blood pressure, when one is evaluating patients with suspected or manifest peripheral arterial disease. In general, measurement during vasodilatation is to be preferred, since curves are easily obtainable.     

列线图模型预测高危糖尿病肾病患者2年内疾病进展的风险

目的 基于卫生部激素与发育重点实验室提出的糖尿病肾脏病(diabetic kidney disease, DKD)风险模型,建立列线图以识别2年内可能出现进展的高危DKD患者。方法 本研究是前瞻性队列研究,筛选符合DKD高风险标准的2型糖尿病患者并随访两年。随访期间进展为DKD的定义为DKD组,未出现进展的定义为非DKD组。通过单、多因素COX回归分析入选患者的基线临床资料和超声指标,建立列线图模型以预测DKD高风险患者2年内出现疾病进展的风险。结果 至随访结束,DKD组患者63例,非DKD组患者308例。生存分析显示DKD高风险患者2年内出现进展的比例为16.98%。多因素Cox回归分析发现,糖尿病病程、肾叶间动脉阻力指数、以及患者合并糖尿病视网膜病变和高血压是DKD高风险患者2年内疾病进展的独立影响因素(均P < 0.05)。基于这四项指标建立的列线图预测模型具有较好的区分度[曲线下面积(area under the curve, AUC)：0.783],其预测准确性高于各预测因子单独预测的AUC(P＜0.05)。此外,该列线图预测DKD进展的概率与实际发生率的一致性较好(χ2^{=6.392, P=0.}592),且具有良好的净收益,表明其在临床决策方面具有良好的应用价值。结论 本研究建立了包含四项常见指标的列线图预测模型,用于识别2年内可能出现进展的高危DKD患者,从而在尿微量白蛋白升高前的“亚临床”阶段即实施早期干预,有望延缓甚至阻止高危患者进一步进展为DKD。     

Effect of meal on retinal blood flow in IDDM patients

OBJECTIVE: The effect of postprandial hyperglycemia on retinal blood flow was examined in 11 adults with insulin-dependent diabetes mellitus (IDDM) and 9 nondiabetic subjects. RESEARCH DESIGN AND METHODS: Retinal blood flow was measured with bidirectional laser Doppler velocimetry before and 60 and 120 min after a 50-g carbohydrate breakfast. Diabetic subjects were studied twice, being randomized to take their usual insulin (isoglycemic study) or to omit their morning short-acting insulin (hyperglycemic study). Nondiabetic subjects were studied once and received no insulin. RESULTS: Plasma glucose rose significantly (from 11.5 +/- 5.2 to 22.1 +/- 5.5 mM, P less than 0.001) during the hyperglycemic study but not during the isoglycemic or nondiabetic studies. There were no significant changes in blood pressure or retinal blood flow in any of the groups studied. CONCLUSIONS: Short-term hyperglycemia does not increase retinal blood flow.     

危重患者腹腔内高压的发生率及其影响因素

目的：观察危重患者腹腔内高压（IAH）的发生率及其影响因素。方法：采用前瞻性队列研究方法,选择我院重症监护病房（ICU）的患者341例,采用经膀胱尿管间接测定方法,每日监测患者lAP,连续监测7d,按IAH的有无分组并进行临床资料比较,计量资料用t检验,计数资料用x^2检验,危险因素以单因素及多因素Logistic回归模型进行分析。结果：341例患者中88例（25．8％）患者发生腹腔内高压（IAH）,15例（4．5％）患者发生腹腔间室综合征（ACS）。腹腔感染,大量液体复苏,肠梗阻,感染性休克,肝功能不全与IAH的发生密切相关（P=0．000,0．000,0．007,0．000,0．000）。结论：IAH的发生在危重患者中较常见,腹腔感染,大量液体复苏,感染性休克,肝功能不全可能是IAH发生的独立危险因素。