Height at diagnosis of insulin dependent diabetes in patients and their non-diabetic family members

Height at the onset of insulin dependent diabetes mellitus was evaluated in 200 newly diagnosed children, 187 non-diabetic siblings, and 169 parents. Diabetic children 5-9 years of age at diagnosis were consistently taller than the national average. Non-diabetic siblings of the same age were also tall. Diabetic children aged 14 or over at diagnosis were short, while their siblings and parents were of normal height. Diabetic children positive for islet cell antibodies were taller than those without islet cell antibodies. No association between height and HLA antigens was found. Non-diabetic siblings at high risk for the disease were closer in height to the diabetic children than were the lower risk, non-diabetic siblings. Siblings, particularly those under 10, were also significantly more obese than the general population. Deviations in growth in patients with insulin dependent diabetes mellitus appear to be related to age at diagnosis and a factor(s) not related to parental height.     

Diabetes in Western Australian children: descriptive epidemiology

The prevalence and incidence of diabetes mellitus in the age group zero to 14 years in Western Australia were determined from a survey by means of Schools Health Services. Additional information from the State's computer-linked hospital records system, the State's only children's hospital, diabetic clinics and physicians enabled virtually complete ascertainment of cases of childhood diabetes. Only 60% of school-age diabetic children were known to school nurses before the survey, but the nurses were able to identify two-thirds of the remainder during the survey. Among non-Aboriginal children, the prevalence of diabetes in the age group zero to 14 years was 0.59 per 1000 children and the incidence was 12.3 per 100,000 children per year. These rates are somewhat lower than those that have been reported from the United Kingdom and North America, and substantially lower than the rates that were reported from Scandinavia. All but one of the diabetic children who were identified required insulin and were assumed to be insulin-dependent. An excess of boys was found. None of 8715 Aboriginal or part-Aboriginal children had insulin-dependent diabetes mellitus, which indicates that this racial group has a low prevalence of this condition. In case--control studies, which used questionnaires for parents, no significant trends were found in relation to the history of immunizations or of specific viral illnesses except for a past history of varicella which was less frequent in diabetic children. A past history of established breast-feeding (of more than one week) was less frequent in diabetic children, as was the ingestion of vitamin C supplements before the onset of diabetes. Some evidence for a seasonality of onset was obtained. The diabetic children were absent from school for more days and had more admissions to hospital than did non-diabetic children. The majority of diabetic children were prescribed insulin twice a day or more often (84%); performed home blood-glucose monitoring (74%); and attended hospital diabetic clinics (91%).     

Type II diabetes of early onset: a distinct clinical and genetic syndrome?

The inheritance of non-insulin-dependent (type II) diabetes was studied by a continuous infusion of glucose test in all available first degree relatives of 48 diabetic probands of various ages and with differing severity of disease. In an initial study of 38 type II diabetic subjects and their first degree relatives six islet cell antibody negative patients with early onset disease (aged 25-40 at diagnosis) were found to have a particularly high familial prevalence of diabetes or glucose intolerance. Nine of 10 parents available for study either had type II diabetes or were glucose intolerant. A high prevalence of diabetes or glucose intolerance was also found in their siblings (11/16;69%). In a second study of the families of a further 10 young diabetic probands (presenting age 25-40) whose islet cell antibody state was unknown a similar high prevalence of diabetes or glucose intolerance was found among parents of the five islet cell antibody negative probands (8/9; 89%) but not among parents of the five islet cell antibody positive probands (3/8;38%). Islet cell antibody negative diabetics with early onset type II disease may have inherited a diabetogenic gene or genes from both parents. They commonly need insulin to maintain adequate glycaemic control and may develop severe diabetic complications. Early onset type II diabetes may represent a syndrome in which characteristic pedigrees, clinical severity, and absence of islet autoimmunity make it distinct from either type I diabetes, maturity onset diabetes of the young, or late onset type II diabetes.     

Type I (insulin dependent) diabetes: a disease of slow clinical onset?

Type I (insulin dependent) diabetes is usually believed to present acutely and it is assumed that metabolic decompensation is sudden. In a prospective family study, however, 10 of 13 subjects developing the disease showed progressive or intermittent development of hyperglycaemia over many months and the others had non-specific symptoms over a long period. All were first degree relatives of a child with type I diabetes; 10 were siblings (aged 5-24) and three were parents (aged 45-58). All possessed HLA-DR4 or DR3, or both, and all but two had been positive for islet cell antibodies for six to 86 months before diagnosis. Ten had non-specific symptoms for two to 14 months before the onset of thirst and polyuria; one remained asymptomatic even when insulin became necessary. Six subjects had an oral glucose tolerance test before clinical onset, of whom five were diabetic by World Health Organisation criteria four, four, six, seven, and 21 months before insulin was needed. Nine showed random blood glucose concentrations above the 97.5th centile (6.3 mmol/l) six to 34 months (median 12) before diagnosis. Two others had a glucose tolerance test result compatible with diabetes but had not reached the stage of needing insulin. Hyperglycaemia is often of insidious onset in type I diabetes, even in children and young adults. Diagnosis will inevitably be late if considered only when acute symptoms of thirst and polyuria develop.     

Intractable diabetic ketoacidosis due to insulin antibody--response to steroid therapy

To examine the effect of steroid therapy on insulin antibody titer in insulin-dependent diabetes mellitus, we studied a 58 year-old gentleman with recurrent diabetic ketoacidosis. No any overt precipitating factors could be accounted for, except limited pancreatic beta cell reserve and high titers of anti insulin antibodies. Despite the persistence of high titers of plasma antiinsulin antibodies, the clinical manifestations of diabetic ketoacidosis improved greatly by the administration of steroid. Nevertheless, the patient still showed the great excursion of plasma glucose concentration.     

Abnormal pancreatic glucagon secretion and postprandial hyperglycemia in diabetes mellitus.

Plasma glucose and glucagon responses to standard meals containing carbohydrate, fat, and protein as in normal diets were studied in 12 subjects with insulin-dependent diabetes and 12 normal subjects. Diabetics had two to three times greater glucagon responses than did normal subjects. Fifteen units of insulin injection did not normalize these excessive glucagon responses, although postprandial hyperglycemia was reduced. Infusion of somatostatin at a dosage of 500 mug/hr prevented glucagon responses and diminished postprandial hyperglycemia by 60%. The combination of insulin and somatostatin caused a progressive fall in plasma glucose levels despite meal ingestion. Somatostatin and insulin, administered subcutaneously in the same syringe, also abolished postprandial hyperglycemia. These studies indicate that excessive glucagon secretion participates in the genesis of diabetic postprandial hyperglycemia. Somatostatin, an inhibitor of glucagon secretion, may thus prove useful as an adjunct to insulin in the treatment of diabetes mellitus.     

Somatostatin receptor expression and biological functions in endocrine pancreatic cells: review based on a doctoral thesis

Type 1 diabetes is resulting from the selective destruction of insulin-producing betacells within the pancreatic islets. Somatostatin acts as an inhibitor of hormone secretion through specific receptors (sst1-5). All ssts were expressed in normal rat and mouse pancreatic islets, although the expression intensity and the co-expression pattern varied between ssts as well as between species. This may reflect a difference in response to somatostatin in islet cells of the two species. The Non-Obese Diabetic (NOD) mouse model is an experimental model of type 1 diabetes, with insulitis accompanied by spontaneous hyperglycaemia. Pancreatic specimens from NOD mice at different age and stage of disease were stained for ssts. The islet cells of diabetic NOD mice showed increased islet expression of sst2-5 compared to normoglycemic NOD mice. The increase in sst2-5 expression in the islets cells may suggest either a contributing factor in the process leading to diabetes, or a defense response against ongoing beta-cell destruction. Somatostatin analogues were tested on a human endocrine pancreatic tumour cell line and cultured pancreatic islets. Somatostatin analogues had an effect on cAMP accumulation, chromogranin A secretion and MAP kinase activity in the cell line. Treatment of rat pancreatic islets with somatostatin analogues with selective receptor affinity was not sufficient to induce an inhibition of insulin and glucagon secretion. However, a combination of selective analogues or non-selective analogues via costimulation of receptors can cause inhibition of hormone production. For insulin and glucagon, combinations of sst2 + sst5 and sst1 + sst2, respectively, showed a biological effect. In summary, knowledge of islet cell ssts expression and the effect of somatostatin analogues with high affinity to ssts may be valuable in the future attempts to influence beta-cell function in type 1 diabetes mellitus, since down-regulation of beta-cell function may promote survival of these cells during the autoimmune attack.     

非胰岛素依赖型糖尿病患者血清中抗GAD抗体的临床意义

目的：探讨谷氨酸脱羧酶抗体（ＧＡＤ－Ａｂ）对糖尿病诊断的临床意义。方法：用间接ＥＩＡ法测定了１１０例初诊为非胰岛素依赖型糖尿病（ＮＩＤＤＭ）患者血清中ＧＡＤ－Ａｂ。结果：１１０例ＮＩＤ－ＤＭ患者中ＧＡＤ－Ａｂ总阳性率为１９．１％，胰岛细胞抗体（ＩＣＡ）阳性率１２．７％，ＩＣＡ阳性者全部检出ＧＡＤ－Ａｂ，而ＧＡＤ－Ａｂ阳性者ＩＣＡ的阳性率６６．７％，而且ＧＡＤ－Ａｂ阳性的病人具有胰岛素依赖型糖尿病（ＩＤＤＭ）的临床特点，即低体重指数及低胰岛素分泌功能。结论：血清中ＧＡＤ－Ａｂ的测定是早期预报及诊断ＩＤＤＭ的最灵敏的免疫标志，而且对于早期诊断“成人晚发自身免疫性糖尿病（ＬＡＤＡ）”，及时给予胰岛素治疗，防止糖尿病眼、肾、神经并发症具有重要的临床意义。     

血清胰岛自身抗体在肝源性糖尿病诊断中的价值

目的探讨血清胰岛自身抗体一谷氨酸脱羧酶抗体（GADA）和胰岛细胞抗体（ICA）在肝源性糖尿病诊断中的价值。方法采用酶联免疫吸附实验测定217例慢性乙型肝炎（CH）、肝硬化（LC）患者血清GADA和ICA，观察GADA、ICA在CH、LC阶段的阳性率及其与糖尿病的关系。结果CH、LC合并糖尿病的患者72％（56／77）循环中存在一种胰岛自身抗体，而血糖正常的CH、LC患者胰岛自身抗体的阳性率为30％（42／140），两组比较差异有显著性（χ2=-36．620，P=0．000）。CH合并糖尿病患者胰岛自身抗体阳性率52％（13／25）明显高于2型糖尿病（NIDDM）合并肝损害的患者8％（2／25）（P〈0．05）。C肽水平下降的CH、LC患者中胰岛自身抗体阳性率70%（24／34）亦明显高与C肽水平正常的患者40%（74／183）（P〈0．05）。结论GADA、ICA在肝源性糖尿病的诊断中有重要参考价值，可作为肝源性糖尿病和2型糖尿病的实验室鉴别诊断指标。     

胰岛移植的研究进展

糖尿病是由多种原因引起的β细胞功能减退,致胰岛素分泌相对或绝对不足引发的糖代谢紊乱,最终导致全身多器官的损害。众所周知,胰岛素的应用虽明显改善了患者的糖代谢紊乱,但无法阻止糖尿病各种并发症的发生及发展,而在体内建立内源性的胰岛素分泌系统才能治愈糖尿病。全胰移植可有效治疗糖尿病,但因其手术创伤大、病死率高、免疫原性大等缺点不再受到人们的青睐,而胰岛移植具有操作简单、创伤小、并发症少等优点,近年来逐渐受到医学界的重视,成为又一新的研究热点。     

三种胰岛自身抗体联合检测对1型糖尿病早期诊断的意义

目的:评价联合检测谷氨酸脱羧酶抗体(GADA)、胰岛细胞抗体(ICA)和胰岛素自身抗体(IAA)对1型糖尿病的早期诊断价值。方法:采用酶联免疫吸附法(ELISA)检测GADA、ICA和IAA;电化学发光法检测患者空腹和餐后2h血清C肽。结果:1型糖尿病患者GADA、ICA和IAA阳性率明显高于2型患者和正常组,P<0.001。GADA在1型糖尿病中的阳性检出率明显高于ICA和IAA组,P<0.01。青少年患者组ICA阳性率高于GADA和IAA组,P<0.001,成年组及老年组患者中GADA阳性明显高于ICA和IAA组,P<0.05。GADA/ICA、GADA/IAA及三种抗体联合检测的阳性率,敏感性和诊断符合率均高于单一抗体检测的阳性率,P<0.05。抗体阳性患者的空腹和餐后C肽水平明显低于抗体阴性患者,P<0.01。结论:自身抗体阳性患者的胰岛功能明显低于阴性患者,表明抗体阳性患者胰岛功能有明显损伤。GADA、ICA和IAA联合检测可以提高诊断敏感性和诊断符合率,对1型糖尿病早期诊断具有重要价值,且青少年期GADA和ICA的联合检测显得尤为重要。     

早期胰岛素强化治疗对初诊2型糖尿病患者胰岛β细胞功能的影响

目的：探讨早期胰岛素强化治疗对伴明显高血糖的初诊2型糖尿病患者胰岛β细胞功能的影响。方法：将80例伴明显高血糖的初诊2型糖尿病患者给予胰岛素强化治疗3月,观察患者治疗前后血糖、胰岛素水平、糖化血红蛋白、胰岛β细胞功能指数、胰岛素抵抗指数变化,以及停药后血糖达标持续时间。结果：80例患者接受胰岛素强化治疗后,空腹及餐后血糖、糖化血红蛋白、胰岛素抵抗指数均较治疗前明显下降,胰岛素分泌水平、胰岛β细胞功能指数较治疗前明显升高。随访6个月,其中36例仅通过饮食控制及体育锻炼即可获得理想的血糖控制。结论：初诊2型糖尿病患者通过早期胰岛素强化治疗后可有效控制血糖,显著改善胰岛β细胞功能,减轻胰岛素抵抗。     

Plasmapheresis in the initial treatment of insulin-dependent diabetes mellitus in children

Several factors indicate that autoimmune mechanisms may play a part in the aetiology of insulin-dependent diabetes mellitus. At the onset of the disease in 10 children (aged 11-16 years) plasmapheresis was performed four times over one to two weeks. Seventeen age-matched children with the same clinical features served as controls. The C-peptide concentrations at onset were the same in the two groups, but after one month the children treated with plasmapheresis had significantly higher values. This difference became even more pronounced after three, nine, and 18 months, both during fasting and at the maximum response to a standardised meal. The study group also had a significantly more stable metabolism, longer partial remission, and no higher insulin requirement. Of the 10 treated children islet-cell cytoplasmic antibodies were present in seven before plasmapheresis and in nine during treatment. The antibodies remained detectable in five and six out of nine patients at one and six months respectively after plasmapheresis. Although the mechanisms are obscure, plasmapheresis performed at the onset of insulin-dependent diabetes mellitus may help to preserve beta-cell function.     

初诊2型糖尿病患者血清铁蛋白检测及其临床意义

目的 观察初诊2型糖尿病患者血清铁蛋白(Serum ferritin,SF)水平的变化,探讨血清SF检测在初诊2型糖尿病患者中的意义。方法 通过比较98例初诊2型糖尿病患者与60例健康对照者的血糖、血脂、胰岛素抵抗指数、胰岛β细胞功能指数及SF等方面的差异,分析SF与血糖、血脂、HOMA-IR、HOMA-β之间的相关性。结果 初诊2型糖尿病患者的血糖、血脂、HOMA-IR和SF水平显著高于健康对照者,而其HOMA-β水平低于健康对照组,pearson相关分析显示初诊2型糖尿病患者血清SF与FBG、HbA1c、TG、TC、、FINS、HOMA-IR呈正相关,与HOMA-β呈负相关。结论 初诊2型糖尿病患者血清SF水平增加与胰岛素抵抗加重和胰岛β细胞分泌功能下降有关。     

活性维生素D3对糖尿病大鼠胰岛β细胞功能影响的研究

目的研究维生素职在高糖诱导的大鼠胰岛B细胞氧化应激中的作用。方法采用MTY比色法分析比较有无添加维生素D3对于不同浓度葡萄糖诱导的大鼠B细胞系min6细胞增殖率的影响,并使用酶联免疫法试剂盒检测胰岛素分泌情况。建立糖尿病大鼠模型模拟疾病进程,研究给药骨化三醇胶丸0．008μg／（kg·d）1对于大鼠血糖、体重变化的影响,并检测血清及胰腺中氧化应激标志物丙二醛（MDA）和谷胱甘肽过氧化物酶（GSH—Px）表达情况。结果维生素D,可以保护高糖诱导的大鼠胰岛B细胞损伤并且抑制p细胞中胰岛素的分泌。动物模型实验显示,给药骨化三醇胶丸对于糖尿病发生及进程影响不大,但是有助于改善糖尿病引起的大鼠体重减轻。对于血清及胰腺MDA和GSH—Px的检测发现,骨化三醇胶丸有助于改善胰腺氧化应激状态并减少胰腺损伤。结论维生素D,可以减少高糖诱导的大鼠胰腺B细胞损伤,并且在糖尿病发生过程中减轻胰腺氧化应激状态,减少胰腺损伤。     

2型糖尿病患者血清超灵敏C反应蛋白水平的检测

目的 探讨2型糖尿病患者血清超灵敏C反应蛋白(hs-CRP)水平与机体胰岛素敏感性的关系。方法 运用高灵敏酶联免疫吸附法检测68例2型糖尿病患者和20名健康对照者的血清hs-CRP水平,同时检测血糖、血清胰岛素、糖基化血红蛋白(HbAlc)、尿白蛋白排泌率和血脂,并计算稳态模型胰岛素抵抗指数(HOMA-IR指数)和胰岛B细胞分泌指数(HOMA-IS)以分别反映机体的胰岛素敏感性和胰岛素分泌功能。结果 2型糖尿病患者的血清hs-CRP水平显著高于对照(P<0.01),HOMA-IR指数和HOM-IS指数均低于正常对照(P<0.01)。进一步将患者按HbAlc分为血糖控制良好组(n=42)和血糖控制欠佳组(n=23)后发现,控制欠佳组的血清hs-CRP水平显著高于控制良好组(P<0.05)。线性相关分析显示,糖尿病患者的血清hs-CRP水平均与HbAlc、空腹血糖、体质量指数、舒张压和HOMA-IS指数呈显著正相关。结论 2型糖尿病患者血清hs-CRP水平高于正常人,而且与糖尿病的发生、发展有密切的关系。     

2型糖尿病患者血清超灵敏C反应蛋白水平的检测

OBJECTIVE: To investigate the relationship between serum level of highly sensitive C-reactive protein (hs-CRP) and insulin sensitivity in type 2 diabetic patients. METHODS: Serum hs-CRP level was determined by highly sensitive enzyme-linked immunosorbent assay (ELISA) in 65 patients with type 2 diabetes and 25 normal controls. Plasma glucose, serum insulin, glycosylated hemoglobin (HbA1c), urinary albumin excretion rate (UAER), plasma lipids and lipoprotein were also measured. Moreover, homeostasis model analysis (HOMA) of insulin resistance index (HOMA-IR) and islet secretion index (HOMA-IS) were calculated to estimate the insulin sensitivity and islet function. RESULTS: In the patients with type 2 diabetes, serum hs-CRP was increased, HOMA-IR index and HOMA-IS index were decreased as compared with the normal control subjects (P<0.01). Moreover, serum hs-CRP was significantly higher in poorly controlled diabetic patients (n=23) with HbA1c >7% than that in well controlled diabetic patients (n=42) with HbA1c<7%. Liner regression analysis in diabetic patients showed that serum hs-CRP was negatively correlated with HOMA-IS index but positively correlated with fasting plasma glucose, body mass index, HbA1c and diastolic blood pressure, respectively. CONCLUSION: Serum HS-CRP level is higher in the patients with type 2 diabetes than in normal subjects, and plays an role in the development and progression of type 2 diabetes mellitus.     

来得时联合普通胰岛素强化治疗初发2型糖尿病疗效观察

目的：探讨早期胰岛素强化治疗初发2型糖尿病方案的优劣。方法：对2006年1月～2009年6月住院初发2型糖尿病患者90例进行回顾分析。空腹血糖（FBG）≥11.1mmol/L,HBA1C≥9.0%。根据当时采用的不同的胰岛素治疗方案,分成A、B、C三组。A组采用来得时联合普通胰岛素治疗,B组采用诺和灵N联合普通胰岛素治疗,C组采用预混胰岛素（诺和灵50R或30R）治疗。三组均在胰岛素治疗基础上,同时应用阿卡波糖、二甲双胍,不用促胰岛素分泌剂。比较三组降糖效果、血糖控制时间、胰岛素总量及低血糖发生率。结果：三组均显示明显的降糖效果,其中以A组来得时联合普通胰岛素治疗方案最优,血糖达标时间最短,胰岛素用量最少,低血糖发生率最低。结论：初发2型糖尿病患者早期胰岛素强化治疗中,来得时联合普通胰岛素能更有效地控制血糖水平,降低高糖毒性,减少胰岛素抵抗,促使胰岛β细胞功能恢复。     

妊娠期糖尿病的发病机制

妊娠期糖尿病(GDM)为糖尿病的一种特殊类型,对母亲和胎儿都有不利影响。GDM孕妇存在比正常孕妇更强烈的胰岛素抵抗,并且胰岛β细胞功能存在缺陷。C反应蛋白、白细胞介素6等炎性因子参与了GDM孕妇慢性炎症的发生。免疫失衡造成细胞毒性因子的释放增加,增加了GDM发生的风险。人类白细胞抗原分子作为免疫调节分子,可能与GDM有一定的关系,GDM孕妇某些人类白细胞抗原基因型频率是增加的。