Urinary growth hormone excretion during puberty in type 1 (insulin-dependent) diabetes mellitus

The excretion of urinary growth hormone was measured by a highly sensitive direct immunoradiometric assay in a cross-sectional study during puberty in 70 children with Type 1 (insulin-dependent) diabetes mellitus and 94 normal children. In normal children (n = 24) and diabetic children (n = 17) overnight urinary growth hormone excretion correlated significantly with the mean overnight plasma concentration (r = 0.70, p less than 0.001, and r = 0.70, p less than 0.001), indicating that urinary GH excretion reflects the circulating endogenous GH level. Overnight urinary growth hormone excretion increased during puberty. In normal and in diabetic children there was a peak in boys at genital stage 4 (both p less than 0.01), and in girls at breast stage 2 (both p less than 0.02). The diabetic children excreted more urinary growth hormone than the normal children at every pubertal stage. Excretion of albumin, retinol binding protein and N-acetyl-beta-D-glucosaminidase was measured in urine from 38 diabetic children. Urinary growth hormone correlated weakly with urinary albumin (r = 0.49, p less than 0.01), retinol binding protein (r = 0.42, p less than 0.01), and N-acetyl-beta-D-glucosaminidase (r = 0.43, p less than 0.01). Urinary GH excretion was not related to blood glucose control (HbA1) in boys (n = 31) or girls (n = 39). The measurement of urinary growth hormone provides an assessment of endogenous growth hormone during puberty in normal and diabetic children. However, caution must be exercised in interpreting urinary growth hormone data from diabetic patients with increased excretion of albumin and retinol binding protein.     

Urinary kallikrein excretion in Type 1 (insulin-dependent) diabetes mellitus

Summary Kidney haemodynamics appear to change after the early phases of diabetic nephropathy: increases in glomerular filtration rate and in renal plasma flow have been widely reported, while kidney size is increased. As the renal kallikrein-kinin system has been demonstrated to regulate kidney blood circulation, we have evaluated the excretion of urinary kallikrein in 87 Type 1 (insulin-dependent) diabetic patients with and without hyperfiltration. Urinary kallikrein excretion was measured in 24-h urine collections. The esterolytic activity was determined by fluorimetric assay. The excretion of urinary kallikreins was significantly higher in hyperfiltering patients (472±125 esterase units/24 h) than in normofiltering (168±77 esterase units/24 h) and control subjects (151±39 esterase units/24 h), p<0.001. Furthermore, we observed a positive correlation between urinary kallikrein excretion and glomerular filtration rate (r=0.785). These data suggest that variations of kallikrein and kinin concentrations may play a role in the alteration of renal haemodynamics in Type 1 diabetes. It is possible that the kinin-kallikrein system, the renin-angiotensin system and the prostaglandins may interact to determine the haemodynamic alterations which are present in the diabetic disease.     

Triphasic changes in selectivity with increasing proteinuria in type 1 and type 2 diabetes

Two indices of the selectivity of proteinuria, the immunoglobulin G (IgG)/albumin and the IgG/transferrin clearance ratios, were studied cross-sectionally and serially over 7 years in a cohort of 52 Type 1 and 60 Type 2 diabetic patients without established diabetic nephropathy. In Type 1 and Type 2 diabetic patients with albuminuria less than 30 micrograms min-1, both protein clearance ratios were significantly higher than in 27 control subjects. As albuminuria increased, there was a decrease in both protein clearance ratios. However, at albumin clearances above 90 nl s-1, equivalent to albumin excretion rates of greater than 250 micrograms min-1, a positive correlation was found in Type 2 diabetic patients between protein clearance ratios and albuminuria. In individual Type 1 and Type 2 diabetic patients with progressively increasing proteinuria, serial measurements of selectivity showed a decline in both protein clearance ratios with the onset of microalbuminuria. Episodes of transient microalbuminuria were also associated with a fall in the IgG/albumin clearance ratio. The results suggest that the selectivity of proteinuria undergoes a triphasic change with the development of diabetic nephropathy. In the first phase, proteinuria is non-selective with IgG clearance equal to or exceeding transferrin or albumin clearance. As microalbuminuria develops, there is a progressive increase in selectivity reflecting the preferential excretion of transferrin and albumin compared with IgG. In later stages of nephropathy, as shown in Type 2 diabetic patients with macroalbuminuria, there is a return to non-selective proteinuria.     

Increased urinary excretion of transferrin in children with type 1 diabetes mellitus.

Urinary transferrin excretion was measured by radioimmunoassay in 74 children with Type 1 diabetes mellitus and in 40 normal children, and compared with urinary excretion of albumin, alpha-1-microglobulin, and N-acetyl-beta-D-glucosaminidase. Urinary transferrin excretion was significantly elevated in diabetic (median (range) 186 (18-1671) mg mol-creatinine-1) compared with normal (85 (27-668) mg mol-creatinine-1) children (p less than 0.001). Seventeen diabetic children had transferrin excretion above the 95th centile for normal children. In contrast there was no significant increase in urinary albumin excretion in the diabetic children although 8 had urinary albumin excretion which exceeded the 95th centile for normal children (6 of these 8 patients having coexistent urinary hyperexcretion of transferrin). Urinary transferrin excretion correlated significantly with urinary albumin excretion in both normal (rs = 0.62, p less than 0.001) and diabetic (rs = 0.61, p less than 0.001) children. The indices of proximal renal tubular function (urinary excretion of alpha-1-microglobulin and N-acetyl-beta-D-glucosaminidase) correlated significantly with transferrin excretion in both diabetic (rs = 0.43 and rs = 0.41, p less than 0.001) and normal (rs = 0.40, p less than 0.02 and rs = 0.53, p less than 0.001) children, but not with albumin excretion (rs = 0.20, p greater than 0.05 and rs = 0.22, p greater than 0.05). In addition urinary transferrin excretion significantly correlated with urinary glucose concentration (rs = 0.34, p less than 0.007) in Type 1 diabetic children. The discrepancy in urinary excretion of transferrin and albumin may reflect impaired proximal renal tubular reabsorption of transferrin and/or altered glomerular basement membrane selectivity for the two proteins.     

Progression of proteinuria in type 1 and type 2 diabetes

A longitudinal study evaluating the time course of the transition from normal to microalbuminuria, and then on to macroalbuminuria, was made over a mean period of 7 years in a cohort of 52 patients with Type 1 diabetes and 61 patients with Type 2 diabetes. Transient episodes of micro- and macroalbuminuria were often observed before the ultimate development of persistent Albustix-positive proteinuria. The transition from normal to microalbuminuria and from micro- to macroalbuminuria was characterized by rises in renal albumin clearance accompanied by lesser rises in total proteinuria. Seven patients with Type 1 and 12 with Type 2 diabetes showed evidence of progression, the interval for the transition from normal to macroalbuminuria varying from 3 to 5 years. In Type 1 diabetic patients, the development of micro- and macroalbuminuria was associated with a decline in renal function and a rise in systolic blood pressure without a significant change in blood glucose control. In Type 2 diabetic patients, the development of microalbuminuria was associated with a small decline in renal function but no change in blood pressure or blood glucose control. It is concluded that the transition from normal to micro- and on to macroalbuminuria may be more rapid then previously reported and varies considerably among individuals.     

No decreased erythrocyte deformability in type 1 (insulin-dependent) diabetes,either by filtration or by ektacytometry

A lower erythrocyte deformability, which causes impairment of the microcirculation, is postulated to contribute to diabetic organ complications. Erythrocyte deformability was measured in four groups of type 1 (insulin-dependent) diabetic subjects and 30 controls by filtration and ektacytometry. Twenty-five patients without overt nephropathy and 12 with leg ulceration were studied. No decreased erythrocyte deformability was found in any of the diabetic groups with either technique, and neither did the total group of 71 diabetic subjects have a lower erythrocyte deformability when compared with the controls. In order to imitate local conditions in the kidney, erythrocyte deformability was also measured in hyperosmolar solutions. Again no differences were found between the diabetic groups separately or as a whole and the controls. Furthermore no correlation was found between erythrocyte deformability and the plasma glucose or glycosylated haemoglobin level.     

Contrasting fibrinolytic responses in type 1 (insulin-dependent) and type 2 (non-insulin-dependent) diabetes.

To study fibrinolysis in relation to microvascular diabetic complications, 20 control subjects were compared with 50 Type 1 (insulin-dependent) diabetic patients of similar age, 20 with no complications, 17 with laser-treated retinopathy, and 13 with neuropathy and retinopathy. None were smokers, hypertensive or had macrovascular disease. Pre- and post-venous occlusion blood samples for tests of fibrinolysis were taken. Median (interquartile range) basal tissue plasminogen activator (t-PA) activity was lower in control subjects (100 (less than 100-100) IU l-1) than diabetic patients (uncomplicated 145 (100-280) IU l-1, p = 0.015; retinopathy 180 (100-228) IU l-1, p = 0.037; neuropathy 210 (125-310) IU l-1, p = 0.004, respectively). Basal t-PA inhibition (PAl-1 activity) was higher in control subjects (5.9 (4.5-9.5) kIU l-1) than diabetic patients (uncomplicated 4.0 (3.3-5.0) kIU l-1, p = 0.001; retinopathy 4.5 (3.1-6.3) kIU l-1, p = 0.058; neuropathy 4.0 (3.0-5.4) kIU l-1, p = 0.015, respectively). Post-venous occlusion t-PA antigen was higher in control subjects (10.2 (7.3-15.1) micrograms l-1) than neuropathic patients (5.5 (4.9-7.3) micrograms l-1, p = 0.004). Other tests showed a consistent, but non-significant, trend towards increased basal fibrinolysis in the Type 1 diabetic patients. The results indicate that Type 1 diabetic patients have enhanced basal fibrinolysis. The diminished response to venous occlusion in neuropathic patients is consistent with an endothelial cell defect.(ABSTRACT TRUNCATED AT 250 WORDS)     

2型糖尿病患者血清脂蛋白(a)水平变化及其意义

目的　探讨２ 型糖尿病血清Ｌｐ（ａ） 水平与尿白蛋白排泄率的关系。方法　应用单克隆抗体酶联免疫吸附法测定了３１ 例非糖尿病患者和８３ 例２ 型糖尿病患者的血清Ｌｐ（ａ） 水平,并分析它与尿白蛋白排泄率（ＵＡＥＲ） 的相关性。８３ 例２ 型糖尿病患者,根据ＵＡＥＲ 将其分为３ 组：①非糖尿病肾病（ＤＮ）者３２ 例（ＵＡＥＲ＜ ２０ μｇ／ｍｉｎ） ;②微量白蛋白尿者３９ 例（ＵＡＥＲ 介于２０～２００ μｇ／ｍｉｎ之间） ;③大量白蛋白尿者１２ 例（ＵＡＥＲ＞ ２００ μｇ／ｍｉｎ） 。结果　（１） 非糖尿病患者和２ 型糖尿病无ＤＮ 者间血清Ｌｐ（ａ）水平无显著性差异〔（８６ ．４４ ±２ ．１０）ｍｇ／Ｌｖｓ（９３ ．６０ ±１ ．８６）ｍｇ／Ｌ,Ｐ＞ ０ ．０５〕;而在２ 型糖尿病微量白蛋白尿者Ｌｐ（ａ）水平显著升高〔（１４１．１９±２ ．５９）ｍｇ／Ｌ,与非糖尿病患者和２ 型糖尿病无ＤＮ者相比,Ｐ均＜０ ．０５〕;２ 型糖尿病并大量白蛋白尿者Ｌｐ（ａ） 水平有进一步升高〔（２４７ ．５７±１ ．９０）ｍｇ／Ｌ,与非糖尿病患者、２ 型糖尿病无ＤＮ者以及２ 型糖尿病并微量白蛋白尿者相比有显著升高,Ｐ均＜０ ．０５〕。（２）２ 型糖尿病患者中, 血清Ｌｐ（     

Lipoprotein (a) and microvascular disease in type 1 (insulin-dependent) diabetes.

The influence of albuminuria and proliferative retinopathy on concentration of serum lipoprotein (a) was examined cross-sectionally in 90 Type 1 diabetic patients. Concentrations of lipoprotein (a) were less in those with normoalbuminuria (90 (8-882) (median (range] U l-1) than in those with micro- or macro-albuminuria (137 (19-1722) U l-1, p less than 0.05). The prevalence of patients whose lipoprotein (a) concentrations were greater than 200 U l-1 was also greater (45% vs 24%, p = 0.03) among patients with albuminuria, but no difference was found between the microalbuminuric and macroalbuminuric groups (53 and 41%, respectively), or between those with or without proliferative retinopathy. The present finding that lipoprotein (a) concentrations may be increased at an early stage of diabetic renal disease may in part account for the excess ischaemic heart disease associated with diabetic nephropathy.     

The natural history of insulin-dependent diabetes mellitus in Denmark: 1. Long-term survival with and without late diabetic complications

All 906 patients with insulin-dependent diabetes mellitus (IDDM) diagnosed before the age of 31 years, prior to 1943, and admitted to the Steno Memorial Hospital were followed until death or until 1 January 1984. In an attempt to identify factors of prognostic importance, we compared patients dying within 35 years of the onset of diabetes with patients surviving for 40 years or more. Three hundred and seventy-seven patients survived for 40 years or more; of these 224 were still alive and invited to a re-examination, in which 184 participated. After 40 years of diabetes, the most frequent complications were impaired vision (due to diabetic retinopathy) and persistent proteinuria. However, 53% had no major complications despite 40 years with IDDM. The 184 re-examined patients (median age 60 years, median diabetes duration 47 years) were all genuine IDDM patients, as defined by stimulated C-peptide levels. Proliferative retinopathy or visual impairment was found in 56% of the 184 patients, abnormal ECG or amputations in 26%, and elevated urinary albumin excretion rate (AER) greater than or equal to 30 mg/24 h) in 45%. Twenty-five per cent had none of these complications. Proliferative retinopathy was associated with elevated AER and raised systolic blood pressure, macroangiopathy with the use of antihypertensive drugs, and proteinuria with low age at diagnosis, large increase in systolic blood pressure, smoking, and insulin-binding antibodies. Sex, age and diabetes duration were not associated with any of these three late diabetic complications.     

Lipids,lipoproteins and apolipoproteins in type 1 (insulin-dependent) and type 2 (non-insulin-dependent) diabetes mellitus

Summary Total plasma cholesterol, triglycerides, VLDL-C, VLDL-TG, HDL-C and the apoproteins A-I, A-II, B and D were measured in 111 male non-obese diabetic patients and in 90 male control subjects of similar age and body weight distribution. Forty-eight patients had Type 1 (insulin-dependent diabetes) and 63 had Type 2 (non-insulin-dependent diabetes); all were in stable metabolic control while following an appropriate diet and therapy with insulin or oral hypoglycemic agents. HDL-C, apoA-I, apoB and the apoA-I/apoA-II ratio were significantly increased in the Type 1 patients, whereas the VLDL-C/VLDL-TG and LDL-C/apoB ratios were decreased significantly. Type 2 diabetics showed low HDL-C and low apoA-I/apoA-II ratio, while the values of apoA-I, A-II, D and the VLDL-C/VLDL-TG ratio were significantly higher than in controls. Type 1 diabetics in ‘fair’ metabolic control presented higher values of TG, VLDL-C, VLDL-TG and apoB than patients in ‘good’ control: lower values of apoA-I and of the ratios apoA-I/apoA-II, apoA-I/apoB and LDL-C/apoB were recorded in the same subgroup. In Type 2 diabetics no significant differences were observed according to metabolic control, with the exception of a higher apo-D value in subjects in ‘fair’ control. The data obtained support the view that good metabolic control may be important for the prevention of a relevant derangement of lipoprotein components, particularly in Type 1 patients. Partially supported by grant No. 83.02521.56 fromConsiglio Nazionale delle Ricerche (CNR), Roma, Italy (Progetto Finalizzato di Medicina Preventiva e Riabilitativa).     

Effect of type I (insulin-dependent) diabetes mellitus on key glycolytic enzymes of red blood cells

Summary The effect of type I (insulin-dependent) diabetes mellitus on the key glycolytic enzymes of red cells was studied. The activities of hexokinase, phosphofructokinase and pyruvate kinase were found to be significantly (p<0.01) increased in diabetic patients. Treatment with insulin restored the enzyme activities to normal. The increased activities of the key enzymes may help to regulate red cell ATP level in response to the elevated Na:K pump rate in diabetes. The increased activities of these enzymes may also be due to a greater proportion of young erythrocytes in diabetic patients because of a shortened red cell life span as compared to normal.     

Indices of renal structure and function in patients with type 1 diabetes mellitus

The evaluation of renal biopsies from diabetic patients rests upon measurements of many structures in glomeruli, the tubules and the interstitium. These individual values can also be expressed as an index of renal structure. To assess the validity of the individual values versus a published index of renal structure, we evaluated glomerular basement membrane width, mesangial volume fraction, other measures of glomerular structure, and percentage glomerulosclerosis in type 1 diabetic subjects with renal function ranging from normal to marked albuminuria, hypertension, and a falling glomerular filtration rate. For all measured structural parameters and for the index, all groups of diabetic patients, even those who had completely normal renal function, had values different from non-diabetic subjects (P<0.001). Furthermore, there was an excellent correlation between the structural index and a similar functional index (r=0.77).     

ELISPOT在1型糖尿病中的应用

酶联免疫斑点技术(ELISPOT)是在单细胞水平定性、定量检测微量抗原特异性T细胞及其分泌的细胞因子的检测技术.因其优势已替代其他T细胞检测技术,故通过对胰岛自身抗原特异性T细胞免疫标志物的检测,在阐明1型糖尿病的发病机制以及对该疾病的预测、分型诊断、判断预后和免疫治疗监测等方面都起着重要的作用.目前,关于ELISPOT的标准化和验证工作已经卓有成效,应用于临床指日可待.     

Urinary excretion of apolipoprotein(a) fragments in type 1 diabetes mellitus patients

High levels of plasma lipoprotein(a) [Lp(a)] represent an independent risk factor for cardiovascular morbidity; however, Lp(a) has not yet been identified as a risk factor for type 1 diabetic patients. Results from the limited number of available studies on plasma Lp(a) levels in relation to renal function in type 1 diabetes mellitus are inconclusive. We hypothesized that only type 1 diabetes mellitus patients with impaired renal function show increased plasma Lp(a) levels, due to decreased urinary apolipoprotein(a) [apo(a)] excretion. We therefore measured urinary apo(a) levels in 52 type 1 diabetes mellitus patients and 52 matched controls, and related the urinary apo(a) concentration to the plasma Lp(a) level, kidney function, and metabolic control. Our findings indicate that patients with incipient diabetic nephropathy as evidenced by microalbuminuria (20 to 200 microg/min) exhibit significantly higher plasma Lp(a) levels (median, 15.6 mg/dL) in comparison to normoalbuminuric patients (median, 10.3 mg/dL) and healthy controls (median, 12.0 mg/dL). Urinary apo(a) normalized to creatinine excretion was significantly elevated in both normoalbuminuric (median, 22.3 microg/dL) and microalbuminuric type 1 diabetic patients (median, 29.1 microg/dL) compared with healthy subjects (median, 16.0 microg/dL) and correlated significantly with Lp(a) plasma levels in both patient and control groups (P < .003). No correlation existed between the Lp(a) plasma level or urinary apo(a) concentration and metabolic control in type 1 diabetes mellitus patients. From these studies, we conclude that urinary apo(a) excretion is significantly increased in type 1 diabetic patients and correlates with plasma Lp(a) levels, and only type 1 diabetic patients with microalbuminuria have higher plasma levels of Lp(a) compared with patients with normoalbuminuria and healthy controls.     

Concordance for Type 1 (insulin-dependent) and Type 2 (non-insulin-dependent) diabetes mellitus in a population-based cohort of twins in Finland

Summary We studied the cumulative incidence, concordance rate and heritability for diabetes mellitus in a nationwide cohort of 13,888 Finnish twin pairs of the same sex. The twins were born before 1958 and both co-twins were alive in 1967. Data on diabetes were derived through computerized record linkage from death certificates, the National Hospital Discharge Register and the National Drug Register. Records were reviewed in order to assign a diagnostic category to the 738 diabetic patients identified. Of these patients 109 had Type 1 (insulin-dependent) diabetes, 505 Type 2 (non-insulin-dependent) diabetes, 46 gestational diabetes, 24 secondary diabetes, 38 impaired glucose tolerance and 16 remained unclassified. The cumulative incidence of diabetes was 1.4 % in men and 1.3 % in women aged 28–59 years and 9.3 % and 7.0 % in men and women aged 60 years and over, respectively. The cumulative incidence did not differ between monozygotic and dizygotic twins. The concordance rate for Type 1 diabetes was higher among monozygotic (23 % probandwise and 13 % pairwise) than dizygotic twins (5 % probandwise and 3 % pairwise). The probandwise and pairwise concordance rates for Type 2 diabetes were 34% and 20% among monozygotic tiwns and 16% and 9 % in dizygotic twins, respectively. Heritability for Type 1 diabetes was greater than that for Type 2 where both genetic and environmental effects seemed to play a significant role.     

Record-high incidence of Type I (insulin-dependent) diabetes mellitus in Finnish children

Aims/hypothesis. In Finland, the incidence of Type I (insulin-dependent) diabetes mellitus in children aged 14 years or under is the highest in the world and the trend in incidence has been increasing. Our aim was to determine the most recent trends in incidence and the age distribution at diagnosis of Type I diabetes. Methods. Data on the incidence of Type I diabetes in Finland nationwide were obtained from two sources: for the period 1965 to 1986 from the Central Drug Registry of the Social Insurance Institution and for the period 1987 to1996 from the prospective childhood Type I diabetes registry. The annual incidence was calculated per 100 000 people. The increase and the trend in incidence were estimated by fitting the linear regression model with the annual incidence data. Results. During 1987 to 1993 the incidence of Type I diabetes seemed to be rather stable at 36 per 100 000 per year. The incidence has continued to increase thereafter and reached 45 per 100 000 per year in 1996. The analysis of the long-term trend in incidence between 1965 and 1996 showed an absolute incidence increase of 0.67 per year on average being 3.4 % compared with the incidence in 1965. The increase from 1987 to 1996 was highest in very young children 1–4 years old at diagnosis. Conclusion/interpretation. The high incidence of Type I diabetes in Finnish children has thus far not levelled off but is increasing further. If the trend continues, the predicted incidence in Finland will be approximately 50 per 100 000 per year in the year 2010. [Diabetologia (1999) 42: 655–660] Received: 15 June 1998 and in final revised from: 14 December 1998     

Magnesium and insulin-dependent diabetes mellitus

There is accumulating evidence that the changes which occur in the metabolism of some micronutrients in diabetes mellitus might have a specific role in the pathogenesis and complications of this disease. Magnesium deficiency is the most evident disturbance of metal metabolism in insulin-dependent diabetes mellitus. Hypomagnesemia has been linked both to the acute metabolic and late chronic complication of diabetes. Of particular concern, is the association between hypomagnesemia and ischemic heart disease and severe retinopathy in humans with diabetes mellitus. Appropriate magnesium supplementation might prove beneficial in normalizing the low plasma and tissue magnesium levels and prevent or retard the development of vascular complications in diabetic patients. However, well designed and documented experiments need to be performed before the rationales for such therapy are well established.     

Autoimmune tolerance and Type 1 (insulin-dependent) diabetes mellitus

The autoimmune process that results in Type 1 (insulin-dependent) diabetes mellitus may be viewed as a failure to develop or maintain tolerance to self-antigens expressed in the islets of Langerhans. During T-cell development in the thymus, cells that are reactive with self antigens encountered there may undergo clonal deletion or, as more recently described, clonal anergy which effectively removes these cells from the pool of mature antigen reactive T cells. For antigens not found in the thymus, tolerance to self antigens is more complex and may depend on site of antigen expression, ambient concentrations of lymphokines, and availability of antigen-presenting cells that can deliver co-stimulatory signals. Transgenic mice in which the majority of T cells express T-cell receptors against self antigens or in which expression of antigens is targeted to peripheral tissues have proven useful for studies of tolerance in both T- and B-cell compartments. In general, T-cell reactivity against foreign antigen expressed on Beta cells does not occur because of the failure to activate T cells reactive with the antigen, termed clonal ignorance. This may be broken with, for example, viral infection or cytokines. In one transgenic model, dendritic cells that surround the islets of Langerhans have been shown to be responsible for presentation of islet antigens to the immune system. B-cell tolerance can also involve mechanisms of clonal deletion or clonal anergy similar to that occurring with T cells. In addition, a mechanism for changing the affinity of the B-cell antigen receptor termed receptor editing has been described, which may play an important role in diversifying the B-cell repertoire while removing self-reactive cells. Tolerance to antigens may also be induciblc. For example, monoclonal antibodies against T-cell epitopes may induce antigen-specific tolerance that is transferable to other animals, and MHC blocking peptides which can inhibit T-cell responses that are restricted by disease associated MHC molecules. In conclusion, although several possible triggers and mechanisms of autoimmune diabetes can be envisioned, none can be excluded by existing data. However, advances in understanding mechanisms of tolerance to islet and other self antigens suggest potentially useful therapeutic approaches to arresting the autoimmune response.     

中国儿童1型糖尿病发病率的研究

目的研究我国儿童１型糖尿病的发病率。方法中国预防医学科学院ＷＨＯＤｉａＭｏｎｄ项目中国协调中心在全国建立了登记网络。１６个省、市和自治区的２０个地区根据该中心的计划和要求,对１９８８～１９９６年期间诊断的＜１５岁的１型糖尿病病例进行了回顾性的登记。该研究覆盖＜１５岁儿童１９００余万,登记到我国九个民族,共发现８８３例１型糖尿病病人。结果显示该时期总的确定校正发病率为０．５９／１０万人年〔９５％可信区间（ＣＩ）：０．５７～０．６０〕,其中男０．５２／１０万人年（９５％ＣＩ：０．５０～０．５４）,女０．６６／１０万人年（９５％ＣＩ：０．６４～０．６８）。按１９９０年全国人口构成比例标化的确定校正发病率为０．５７／１０万人年。结论我国儿童１型糖尿病的发病率在逐年上升;发病率随年龄的增长而增加;民族间的发病率差异达１２倍;发病率在不同地区之间呈现明显的南低北高现象。