NIDDM肾病患者肾小管间质病变的研究

本研究着重观察了２６例非胰岛素依赖性糖尿病（ＮＩＤＤＭ）肾病患者肾小管间质病变的特点，包括肾小管功能的改变、肾组织学检查及部分患者的尿ＥＧＦ，对小管间质损伤在糖尿病肾病（ＤＮ）发生发展中的作用作了初探。结果发现：①ＮＩＤＤＭ肾病小管间质功能受损具有无明显节段性分布的特点，既有近端小管细胞损伤，也有远端小管的损伤；在形态学上表现为肾小管萎缩、基膜增厚、间质扩张、弥漫炎细胞浸润及不同程度的纤维化。②在肾小球滤过功能明显受损之前，小管间质病变即已出现，并随着肾功能的恶化而逐步加重，提示小管间质损害在ＤＮ的发生发展中起着与肾小球病变同样重要的作用。③肾功能未明显受损、小管间质病变程度较轻的ＤＮ患者，尿ＥＧＦ明显增高。随着肾功能的明显恶化，小管间质萎缩纤维化的加重，尿ＥＧＦ排泄量也逐渐降低，表明ＥＧＦ很可能参与了ＤＮ小管间质病变，在其损伤的早期阶段起了一定作用。     

The inflammatory consequences of psychologic stress: relationship to insulin resistance, obesity, atherosclerosis and diabetes mellitus, type II

Inflammation is frequently present in the visceral fat and vasculature in certain patients with cardiovascular disease (CVD) and/or adult onset Diabetes Mellitus Type II (NIDDM). An hypothesis is presented which argues that repeated acute or chronic psychologically stressful states may cause this inflammatory process. The mediators are the major stress hormones norepinephrine (NE) and epinephrine (E) and cortisol together with components of the renin-angiotensin system (RAS), the proinflammatory cytokines (PIC), as well as free fatty acids (ffa), the latter as a result of lipolysis of neutral fat. NE/E commence this process by activation of NF(kappa)B in macrophages, visceral fat, and endothelial cells which induces the production of toll-like receptors which, when engaged, produce a cascade of inflammatory reactions comprising the acute phase response (APR) of the innate immune system (IIS). The inflammatory process is most marked in the visceral fat depot as well as the vasculature, and is involved in the metabolic events which culminate in the insulin resistance/metabolic syndromes (IRS/MS), the components of which precede and comprise the major risk factors for CVD and NIDDM. The visceral fat has both the proclivity and capacity to undergo inflammation. It contains a rich blood and nerve supply as well as proinflammatory molecules such as interleukin 6 (IL-6), tumor necrosis factor alpha (TNFalpha), leptin, and resistin, the adipocytokines, and acute phase proteins (APP) which are activated from adipocytes and/or macrophages by sympathetic signaling. The inflammation is linked to fat accumulation. Cortisol, IL-6, angiotensin II (angio II), the enzyme 11(beta) hydroxysteroid dehydrogenase-1 and positive energy balance, the latter due to increased appetite induced by the major stress hormones, are factors which promote fat accumulation and are linked to obesity. There is also the capacity of the host to limit fat expansion. Sympathetic signaling induces TNF which stimulates the production of IL-6 and leptin from adipocytes; these molecules promote lipolysis and ffa fluxes from adipocytes. Moreover, catecholamines and certain PIC inhibit lipoprotein lipase, a fat synthesizing enzyme. The brain also participates in the regulation of fat cell mass; it is informed of fat depot mass by molecules such as leptin and ffa. Leptin stimulates corticotrophin releasing hormone in the brain which stimulates the SNS and HPA axes, i.e. the stress response. Also, ffa through portal signaling from the liver evoke a similar stress response which, like the response to psychologic stress, evokes an innate immune response (IIR), tending to limit fat expansion, which culminates in inflammatory cascades, the IRS-MS, obesity and disease if prolonged. Thus, the brain also has the capacity to limit fat expansion. A competition apparently exists between fat expansion and fat loss. In "western" cultures, with excessive food ingestion, obesity frequently results. The linkage of inflammation to fat metabolism is apparent since weight loss diminishes the concentration of inflammatory mediators. The linkage of stress to inflammation is all the more apparent since the efferent pathways from the brain in response to fat signals, which results in inflammation to decrease and limit fat cell mass, is the same as the response to psychologic stress, which strengthens the hypothesis presented herein.     

心理应激对Ⅱ型糖尿病人糖代谢影响的对照研究

应激与Ⅱ型糖尿病人糖代谢之间的关系研究已经进行多年,尤其近十五年有了相当多的文献报道。如Ｇｒａｎｔ等研究发现急性生活事件尤其是急性负性生活事件与糖尿病人症状的加重有关。ＭｃＣｌｅｓｋｙ等发现糖尿病人表现出对手术应激的高血糖反应。但ＮａｌｉｂｏｆｆＣｏｈｅｍ等人的研究结果显示尽管躯体性应激(姿势限制、夹手)和心理性应激(心算)使血浆儿茶酚胺水平升高,但两组病人的血糖水平并无显著改变[1]。可见,应激对糖尿病人糖代谢的影响尚未能得出一确切的结论。以往的研究大多缺乏糖尿病人的对照组,而且研究的结果易受病情、饮食…     

2型糖尿病患者动态血压及心率变异与肾病的相互关系

目的：探讨血压增高、血压昼夜节律异常和自主神经病变对糖尿病肾病的影响。方法：同步监测３５例糖尿病肾病患者、３５例糖尿病正常白蛋白尿患者和３５例正常对照组的动态血压和动态心电图。结果：糖尿病肾病组２４小时血压较正常白蛋白尿组和对照组明显增高,昼夜平均动脉压差值百分率下降（ｐ〈０．００１）;糖尿病正常白蛋白尿组虽然２４小时平均血压与对照组无明显差异,但却已存在夜间血压升高,昼夜平均动脉压差值百分率下降（ｐ〈０．０５～０．００１）;糖尿病肾病组ＨＲＶ指标较糖尿病正常白蛋白尿组和对照组显著减小（Ｐ〈０．０１～０．００１）;糖尿病正常白蛋白尿组ＨＲＶ各项指标也较对照组减小（Ｐ〈０．０１）。结论：糖尿病肾病的发生、发展与血压升高、血压昼夜节律异常和糖尿病自主神经病变有关。     

非胰岛素依赖型糖尿病体内氧化代谢改变及与高血压的关系

目的 :评价氧化损伤及抗氧化酶活性对非胰岛素依赖型糖尿病即Ⅱ型糖尿病 (NIDDM )及其伴发高血压 (HT)的影响。方法 :采用鲁米诺依赖的中性粒细胞化学发光法 ,对 136例NIDDM患者 (其中 70例不伴有HT ,6 6例伴有HT)及 30例年龄匹配的健康对照者 ,检测其外周血中性粒细胞产生氧自由基 (OFR)的水平。采用化学定量法 ,测定其血浆脂质过氧化终末产物———丙二醛 (MDA)的浓度及抗氧化酶———超氧化物歧化酶 (SOD)、谷胱甘肽过氧化物酶 (GSHPx)的活性。结果 :NIDDM伴发HT组 ,其PMN -CL峰值、积分和吞噬指数均明显高于NIDDM不伴HT组及健康对照组 ;血浆MDA浓度较后两组也明显升高 (P均 <0 .0 1) ;NIDDM组及NIDDM伴发HT组的血浆SOD和GSHPx活性较正常对照组均明显降低 (P均 <0 .0 1) ;但与NIDDM组相比 ,NIDDM伴发HT组的血浆SOD和GSHPx活性其差异无显著性 (P均 >0 .0 5 ) ;PMN -CL峰值与MDA呈明显正相关 (r=0 .7486 ,Y =15 9.8X 132 .2 ,P <0 .0 1,n =6 6 ) ,与SOD活性呈明显负相关 (r =- 0 .6 471,Y =5 .6X 112 7.4,P <0 .0 5 ,n =6 6 )。结论 :NIDDM患者体内已存在着氧化损伤 ,而在NIDDM伴发HT时氧化损伤进一步加重 ,提示氧化损伤对NIDDM患者HT的发生发展可能有着病因学意义     

益津降糖口服液的降糖降血脂作用

益津降糖口服液一次或多次给药能显著降低四氧嘧啶糖尿病小鼠、大鼠的血糖 ;有明显的耐糖作用 ;口服后 1h起效 ,2h血糖下降最显著 ,延长到 8h ;显著降低血清胆固醇 (Tc)和甘油三酯 (TG)含量 ;能降低乳酸含量并增加免疫器官的重量     

Randomized clinical trial of lifestyle interventions in Pima Indians: a pilot study

A pilot trial was conducted to test adherence to specific lifestyle interventions among Pima Indians of Arizona, and to compare them for changes in risk factors for diabetes mellitus. Ninety-five obese, normoglycaemic men and women, aged 25–54 years, were randomized to treatments named ‘Pima Action’ (Action) and ‘Pima Pride’ (Pride), which were tested for 12 months. Action involved structured activity and nutrition interventions, and Pride included unstructured activities emphasizing Pima history and culture. Adherence to interventions, changes in self-reported activity and diet, and changes in weight, glucose concentrations, and other risk factors were assessed regularly. Thirty-five eligible subjects who had declined randomization were also followed as an ‘observational’ group and 22 members of this group were examined once at a median of 25 months for changes in weight and glucose concentration. After 12 months of intervention, members of both intervention groups reported increased levels of physical activity (median: Action 7.3 h month⁻¹, Pride 6.3 h month⁻¹, p < 0.001 for each), and Pride members reported decreased starch intake (28 g, p = 0.008). Body mass index, systolic and diastolic blood pressures, weight, 2-h glucose and 2-h insulin had all increased in Action members (p < 0.003 for each), and waist circumference had decreased in Pride members (p = 0.05). Action members gained more weight than Pride members (2.5 kg vs 0.8 kg, p = 0.06), and had a greater increase in 2-h glucose than Pride members (1.33 mM vs 0.03 mM, p = 0.007). Members of the observational group gained an average of 1.9 kg year⁻¹ in weight and had an increase of 0.36 mM year⁻¹ in 2-h glucose. Sustaining adherence in behavioural interventions over a long term was challenging. Pimas may find a less direct, less structured, and more participative intervention more acceptable than a direct and highly structured approach. © 1998 John Wiley & Sons, Ltd.     

Autoantibodies to glutamic acid decarboxylase and phenotypic features associated with early insulin treatment in individuals with adult-onset diabetes mellitus

We investigated the association of serum antibodies to glutamic acid decarboxylase (GADab) with early start of insulin treatment (≤ 1 year from diagnosis, or ≤ 2 years from diagnosis) using data from a representative sample of 374 adult-onset insulin-treated individuals from the Tasmanian Diabetes Register. Furthermore, we examined whether this association was stronger than the phenotypic characteristics (age at diagnosis, sex, family history of diabetes, level of obesity, duration of diabetes) often used for diabetes classification. In this cohort, 35.9 % of males and 38.5 % of females were GADab positive. Within the first year from diagnosis, 78.4 % of GADab positive people compared to 44.0 % of GADab negative people (p < 0.001) had started insulin treatment. Univariate associations with insulin treatment ≤ 1 year from diagnosis included GADab positivity, no family history of diabetes, lower BMI for men, and GADab positivity and lower BMI for women. In multivariate models, significant associations with insulin treatment ≤ 1 year from diagnosis included a family history of diabetes (OR = 0.47, 95 % CI = 0.23–0.95) and GADab positivity (OR = 2.19, 95 % CI = 1.01–4.73) for men, but only GADab positivity (OR = 7.53, 95 % CI = 3.09–18.30) for women. Age at diagnosis was not associated with insulin treatment ≤ 1 year or ≤ 2 years from diagnosis for either sex. These findings indicate that a positive GADab test result is strongly associated with start of insulin treatment within 1 or 2 years from diagnosis, more so than characteristics such as level of obesity and age at diagnosis. © 1998 John Wiley & Sons, Ltd.     

The Role of Insulin Resistance in the Natural History of Type 1 Diabetes

It is well established that peripheral insulin sensitivity is a critical factor in the aetiology of non-insulin dependent (Type 2) diabetes mellitus (NIDDM). Insulin resistance may also play a role at various stages in the natural history of insulin dependent (Type 1) diabetes (IDDM) and this was the topic of a workshop held in London on Friday 14 July 1995. The mechanisms of insulin resistance in IDDM are ill-defined but probably include ‘glucose toxicity’. In the pre-diabetic period, insulin resistance may affect rates of progression to frank hyperglycaemia. Following the clinical onset of IDDM, insulin resistance could influence the length of the ‘honeymoon period’, diabetic control and patterns of growth during puberty, insulin requirements and blood glucose control at any time, the birth weight of infants born to diabetic mothers, and, through an effect on lipid metabolism and hypertension, ultimately contribute to the excess mortality associated with IDDM. In NIDDM, insulin resistance could influence rates of progression to insulin dependence. Treatment using insulin enhancers in NIDDM patients with autoimmune changes might delay or arrest their usual high-risk of progression to insulin dependence. As it is likely that insulin resistance has a wide-ranging influence on the natural history of diabetes in IDDM patients we suggest that treatment with insulin enhancers may prove beneficial in selected patients. © 1997 by John Wiley & Sons, Ltd.