Central fat predicts deterioration of insulin secretion index and fasting glycaemia: 6-year follow-up of subjects at varying risk of Type 2 diabetes mellitus.

AIMS: To examine the relationships between body composition and changes in fasting glycaemia, and in indices of insulin secretion and insulin action over 6 years in females with a family history of Type 2 diabetes with or without prior gestational diabetes ('at risk' group, AR) and control females (control group, C). METHODS: At baseline and at follow-up, an oral glucose tolerance test and dual energy X-ray absorptiometry assessment of body composition were performed. Indices of insulin resistance (HOMA R') and insulin secretion (HOMA beta') were obtained from fasting insulin and glucose concentrations. RESULTS: At baseline, the groups were similar for age, body mass index, fasting levels of plasma glucose and insulin, HOMA R' and HOMA beta'. Despite similar total body fatness, AR had significantly greater waist circumference and central fat (both P < 0.02) compared with C. At follow-up there was a significant increase in central adiposity only in AR, and the fasting plasma glucose (FPG) level was higher in AR compared with C (5.0 +/- 0.2 vs. 4.3 +/- 0.2 mmol/l, P = 0.02). This rise in plasma glucose in AR was related to a decline in HOMA beta' (r = 0.45, P = 0.0065). Both the baseline and the increments in total and central abdominal fat mass were associated with the time-related decline in HOMA beta'. CONCLUSIONS: Six years after initial assessment, AR showed deterioration in FPG levels due predominantly to a decline in insulin secretion index without major change in insulin resistance index. Importantly, baseline body fatness (especially central adiposity), as well as increases in fatness with time, were the major predictors of the subsequent decline of insulin secretion index and the consequent rise in FPG.     

杜仲对糖尿病大鼠扑捉行为和阴茎组织神经传导通路的影响

目的:探讨杜仲改善勃起功能的药效和病理学机制。方法:雄性糖尿病(DM)大鼠30只随机分为3组:A组(10只,DM大鼠赋形剂灌胃组)、B组(10只,DM大鼠西地那非灌胃组)、C组(10只,DM大鼠杜仲灌胃组)及10只正常对照组大鼠(赋形剂灌胃,D组);灌胃4周后观察4组大鼠扑捉行为,透射电镜检查阴茎组织有髓神经纤维超微特征;用免疫组化二步法显示阴茎组织中神经元型一氧化氮合酶(nNOS)的表达。结果:与A组比较,C组大鼠扑捉次数显著增多(P<0.05),阴茎组织中nNOS表达显著增强(P<0.001)。透射电镜显示:A组大鼠阴茎组织有髓神经纤维排布失序,部分变性、板层分离形成透明空泡或网络状,C组大鼠有髓神经纤维排列规整,板层结构清晰。结论:杜仲可通过减轻有髓神经的损伤、增强阴茎组织中nNOS表达改善ED。     

Calorie restriction increases serum parathyroid hormone and decreases serum calcitonin levels in patients with maturity onset diabetes mellitus

Calorie restriction is important in managing patients with maturity onset diabetes mellitus (NIDDM). The effect of such restriction on calcium metabolism is not known. The objective of this study was to determine whether patients on calorie restricted diets would show any modification of parathyroid hormone (PTH) and calcitonin (CTN). The serum levels of PTH and CTN were measured by radioimmunoassays in 269 patients with NIDDM. The patients were divided into two groups depending on the intake of calorie, and PTH and CTN were monitored for 2 years. Plasma levels of vitamin D were measured by competitive protein binding assays before and after each program. The level of PTH (520.8±266.0 pg/ml) (mean±S.D.) was significantly (P<0.01) higher in 109 diabetic patients whose calorie intake was restricted for 2 years (diet (D) group) as compared with that (256.6±103.8 pg/ml) of 160 diabetic patients whose calorie intake was not restricted (non-diet (ND) group). The daily oral calcium intake of the two groups did not differ significantly. We found no significant difference in the serum PTH level in the ND groupVS. normal control subjects (248.8±98.4, N=78). The serum calcium concentration and the amount of calcium excreted in urine were slightly but significantly (P<0.01) lower in the D than in the ND group. The rate of tubular reabsorption of phosphate (% TRP) was significantly lower in the D group than that in the ND group (P<0.01). The serum CTN level was significantly (P<0.01) lower in the D group (33.9±11.3 pg/ml) than in the ND group (64.9±21.2 pg/ml) 2 years after each treatment. The plasma 1,25-(OH)₂-vitamin D level was significantly (P<0.01) lower in the D group (22.2±6.6 pg/ml) than in the ND group (50.6±4.2 pg/ml). When the restriction of calorie intake in the D group was canceled, their PTH levels decreased, which was accompanied by increase in the 1,25-(OH)₂-vitamin D levels, whereas their CTN levels were unchanged. These observations suggested that a restricted calorie intake is a risk factor for secondary hyperparathyroidism as well as for a low serum level of CTN in patients with NIDDM.     

Novel enzyme immunoassay of anti-insulin igG in human serum

A novel enzyme immunoassay of anti-insulin IgG in human serum is described. A serum sample containing anti-insulin IgG was treated with dextran-charcoal at pH 6.0 to remove endogenous insulin and subsequently incubated with dinitrophenyl biotinyl nonspecific rabbit IgG-insulin conjugate. The reaction mixture was further incubated with a rabbit (antidinitrophenyl bovine serum albumin) IgG-coated polystyrene ball to trap the complex formed between anti-insulin IgG and the conjugate. After washing to eliminate nonspecific IgG in the test serum, the polystyrene ball was incubated with dinitrophenyl-L-lysine to elute the complex. The eluate was incubated with an avidin-coated polystyrene ball. Finally, the amount of human anti-insulin IgG in the complex trapped onto the avidin-coated polystyrene ball was measured by incubation with rabbit (antihuman IgG (γ-chain)) Fab'-peroxidase conjugate. This enzyme immunoassay was 1,000-fold more sensitive than the conventional enzyme immunoassay, in which an insulin-bovine serum albumin-coated polystyrene ball was incubated with a serum sample containing anti-insulin IgG and subsequently with rabbit (antihuman IgG (γ-chain)) Fab'-peroxidase conjugate. The principle of the novel enzyme immunoassay can be used to more sensitively measure antibodies for most kinds of haptens and antigens than the conventional enzyme immunoassay.     

大黄对实验性糖尿病大鼠肾脏肥大及高滤过作用的影响

肾脏肥大和高滤过是糖尿病肾病出现最早的病理生理特征。本研究利用中药大黄抑制糖尿病的肾脏肥大,试图达到控制其高滤过现象。实验结果表明,大黄能明显地抑制糖尿病肾脏肥大及其组织中蛋白质、DNA含量的增加;大黄治疗组的菊粉清除率明显低于非治疗组;此外,大黄还能使糖尿病血清甘油三酯、胆固醇水平降低。结论:大黄可以通过影响糖尿病肾病肾脏肥大,降低高滤过和纠正血脂代谢紊乱,治疗实验性糖尿病肾病动物模型。     

糖尿病中促动脉粥样硬化因素的探讨

我们对64例糖尿病患者和20名正常人的糖代谢、脂代谢、血小板和血管内皮细胞前列腺素代谢的水平进行了临床观察。发现糖尿病患者载脂蛋白B、低密度脂蛋白胆固醇、总脂固醇、甘油三酯和血栓素B_2的浓度均有不同程度的升高,而载脂蛋白A_1、高密度脂蛋白胆固醇和6-酮前列腺素F_(1α)的浓度则下降。同时糖代谢异常与脂代谢紊乱、糖代谢异常与前列腺素代谢物水平、以及脂代谢紊乱与前列腺素代谢物水平之间均无明显关系。推想糖尿病中促动脉粥样硬化的各种高危因素可能从不同的角度作用于血管壁,促进动脉粥样硬化的发生和发展。     

A Ro/SS-A auto-antibody positive mother's infant revealed congenital complete atrioventricular block,followed by insulin dependent diabetes mellitus and multiple organ failure

We experienced a congenital complete atrioventricular block infant who was born from a Ro/SS-A antibody positive mother. Ro/SS-A antibody was also found in this baby which was presumed to be mediated by the maternal placenta. Temporary cardiac pacing was required at birth and pacemaker implantation was performed at 9 months. At 11 months of age, the baby fell into shock and experienced multiple organ failure because of diabetes mellitus-induced coma. The association between congenital complete heart block and the Ro/SS-A antibody is well known. However, the accompaniment of insulin-dependent diabetes mellitus has not been reported previously. As the Ro/SS-A antigen appears in the cytoplasm of many tissues, the possibility of an association between Ro/SS-A antibody and diabetes mellitus is difficult to deny. We report this rare case to draw attention to the possibility that babies who are born from an Ro/SS-A antibody positive mother may develop diabetes mellitus as well as congenital complete heart block.     

Skeletal Muscle Adaptations to Physical Training in Type II (Non-insulin-dependent) Diabetes Mellitus

Seven middle-aged men with manifest type II diabetes mellitus underwent an endurance training programme for 10–15 weeks. The maximal aerobic capacity, as well as the endurance capacity, was improved by 10% (p<0.05). The intramuscular glycogen store increased by more than 80% (p<0.05) from 350 μmol/g dw (dry weight), and the activities of citrate synthase and 3-hydroxy-acyl-CoA dehydrogenase increased by more than 50% (p<0.05) and 30% (p<0.05). The activity of glycogen synthase was decreased by approximately 20% (p<0.05), whereas lactate dehydrogenase remained unchanged. Capillaries/fibre and fibre area increased by more than 50% (p<0.05) and 30% (p<0.05) leaving the area of supply constant. Training did not influence fasting blood lipids and glucose, glycosylated hemoglobin, oral glucose tolerance, and insulin response to an oral glucose load measured 72 hours post-exercise. It is concluded that patients with manifest type II diabetes, as normoglycaemic individuals, adapt to physical training. However, no persistent effect on glucohomeostasis and lipaemia is produced by short-term training in the diabetic patients.     

Effect of morphological abnormalities on blood retinal barrier permeability in diabetic retinopathy

The morphological base for the impaired function of the blood retinal barrier was studied in 50 eyes of 10 insulin dependent and 21 non-insulin dependent patients with various levels of diabetic retinopathy. The permeability of the blood retinal barrier (P_BRB) was determined by vitreous fluorophotometry with correction for autofluorescence, lenstransmission and non-protein bound plasma fluorescein concentration. Morphological abnormalities of diabetic retinopathy assessed by fundus photography and fluorescein angiography were individually scored on a decimal scale and related to the P_BRB by multiple regression analysis. The P_brb was not correlated to morphological abnormalities of non-proliferative retinopathy [(1) microaneurysms, (2) hard exudates, (3) soft exudates, (4) intraretinal hemorrhages, (5) fluorescein leakage, and (6) capillary closure, p > 0.3]. The P_BRB was correlated to morphological abnormalities of (pre)proliferative retinopathy [(1) intraretinal microvascular abnormalities (S_irma) and (2) new vessels (S_neo): p_brb = A – B.S_IRMA – C.S_neo with P_BRB in nm/sec, A = 1.5 ± 0.5, B = 0.9 ± 0.2 and C = 1.7 ± 0.4, R² = 0.65, p < 0.0001]. It can be concluded that the increased blood retinal barrier permeability in diabetic patients is mainly due to (pre)proliferative abnormalities and not to non-proliferative abnormalities.     

血管内皮生长因子在糖尿病大鼠视网膜中的表达

目的 :利用糖尿病大鼠动物模型 ,通过大鼠视网膜中血管内皮生长因子 ( vascular en-dothelial growth factor,VEGF)的表达情况 ,探讨 VEGF在糖尿病视网膜病变 ( diabetic retinopa-thy,DR)发展过程中作用机理。方法 :复制链脲佐菌素 ( streptozocin,STZ)糖尿病大鼠动物模型 ,取不同组、不同时期大鼠视网膜 ,利用免疫组织化学及原位杂交方法 ,检测 VEGF蛋白质及 m RNA的表达情况。结果 :1正常对照组 ( M)、血糖恢复组及糖尿病 1个月组 ( M1)大鼠视网膜均无 VEGF蛋白质及 m RNA的阳性表达 ;2糖尿病 3个月组 ( M3 )未见 VEGF m RNA表达 ,而在内核层及节细胞层有 VEGF蛋白表达阳性 ( 34%) ,此表达与胶质纤维酸性蛋白 ( GFAP)染色阳性细胞相同 ;3糖尿病 5个月组 ( M5) VEGF m RNA表达阳性率为 67%,表达位于视网膜各层 ,内界膜中的表达与 GFAP免疫组化阳性分布相同 ,VEGF蛋白质表达强阳性 ( 89%) ,主要位于内核层、节细胞层的细胞及血管上。结论 :VEGF在 STZ大鼠视网膜中的表达与病程相关 ,而且 VEGF的产生存在着自分泌和旁分泌多种途径