Fulminant type 1 diabetes mellitus-like presentation in a Hispanic woman in the United States

Aim

To report the first case of fulminant-like type 1 diabetes mellitus in a Hispanic woman from the United States.

Method

The clinical presentation and laboratory data is presented of a Hispanic woman that was diagnosed with fulminant type 1 diabetes mellitus with a review of the literature.

Results

An 18-year-old female presented with 1 week of polydyspea and polyuria. The patient was seen by her primary care doctor and found to have an elevated blood glucose. On presentation to the hospital, she was found to be in diabetic ketoacidosis. The laboratory analysis showed a C-peptide of 0.6 ng/mL and a glycohaemoglobin A_1c of 6%. The patient had antibodies positive for glutamic acid decarboxylase. The patient was diagnosed with fulminant type 1 diabetes mellitus and was discharged in stable condition on basal/bolus subcutaneous insulin.

Conclusion

Fulminant type 1 diabetes mellitus is a recently described presentation of diabetes mellitus that has been predominately reported in Japan and other Asian countries. The classical presentation includes rapid onset on ketosis within 1 week of symptoms of hyperglycaemia, with a near-normal glycohaemoglobin and absence of C-peptide. With the majority of case being reported from Asia, it has been hypothesized that there is a genetic determent that predisposes Asian individuals to develop fulminant type 1 diabetes mellitus. The addition of the case to the medical literature expands the focus of fulminant type 1 diabetes mellitus beyond the Asian population and supports the need that further research.     

1型糖尿病诊断初期某些细胞因子的改变

目的 探讨细胞因子（CK）在1型糖尿病中的作用,了解其与糖尿病HLA易感基因及糖代谢的关系。方法 放免法或酶免法检测新诊断1型糖尿病病人血清6种CK、胰岛素和C肽;斑点杂交法检测4种糖尿病HLA易感基因;微柱法测定HbA1c。用SPSS软件处理数据。结果 病人组IL－2、IL－4低于对照组,IL－1β、IFN-γ/IL-4、IL－12／IL－4比值,都显著高于对照组;IFN－γ、IL-4、IL－1β分别与IL－12正相关,IL－12／IL－4与IFN－γ／IL－4正相关;空腹胰岛素与IL－1β和空腹C肽与IL－12分别呈正相关。结论 新诊断1型糖尿病病人存在IL－4、IL－2低下及IL－2β的分泌增高;1型糖尿病病人存在TH1优势;IL－12与IL－4正相关,表明了它们对TH1、TH2细胞的调节关系;CK与HbA1无显著相关性;HLA－DQB1＊0201携带者TNF－α较高。     

Apolipoprotein (a) levels in type 1 and type 2 diabetes mellitus

Type 1 and type 2 diabetes mellitus are both characterized by increased cardiovascular mortality and morbidity. Since several reports have indicated that apolipoprotein (a) [apo (a)] levels are positively associated with an increased risk of macrovascular disease, we investigated whether apo (a) levels are elevated in both types of diabetes mellitus and may thus represent an independent risk factor for atherosclerotic disease. Apo(a) concentrations in type 1 diabetic patients were not significantly different from matched controls (276±78 vs 149±46 units/l). Type 2 diabetic patients had considerably higher levels of apo (a) than matched controls (471±89 vs 221±61 units/l,P=0.06), though the difference was not statistically significant. However, concentrations of apo (a) were above 300 units/l in 36% of type 1 and 67% of type 2 diabetic patients, but in only 14% and 25% respectively of matched control subjects. Plasma triglycerides were positively and independently correlated with apo (a) levels in both diabetic and non-diabetic subjects. On the other hand, no significant correlation was found between apo (a) levels and glycosylated haemoglobin, total cholesterol or high density lipoprotein cholesterol in any of the groups studied. In conclusion, apo (a) levels are not significantly elevated either in type 1 or type 2 diabetic patients without proteinuria and in moderate metabolic control; however, levels above 300 units/l were 2.6 times more frequent in both types of diabetes mellitus than in carefully age-, sex-, and weight-matched control subjects.     

Different contribution of class II HLA in fulminant and typical autoimmune type 1 diabetes mellitus

Aims/hypothesis Fulminant type 1 diabetes, which is characterised by a markedly acute onset of diabetes and an absence of islet-related autoantibodies, accounts for 20% of type 1 diabetes in Japan. We aimed to clarify the contribution of the HLA subtype to fulminant type 1 diabetes in Japanese. Methods We determined the serological subtypes of HLA-A, -DR and -DQ in 115 patients with fulminant type 1 diabetes, 98 patients with typical type 1A diabetes and 190 normal control subjects. Results The frequency of HLA-DR4, but not DR9, was significantly higher in fulminant type 1 diabetes, while those of HLA-DR1, DR2, DR5 and DR8 were significantly lower than those in controls. In contrast, DR9 but not DR4 was more frequent and DR2 was extremely rare in typical type 1A diabetes. Haplotype analysis revealed that DR4-DQ4 was significantly more frequent, and both DR2-DQ1 and DR8-DQ1 were less frequent in fulminant diabetes. In type 1A diabetes, DR2-DQ1 was extremely rare while DR9-DQ3 was significantly more frequent. In the combination analysis, the homozygotes of DR4-DQ4 in fulminant type 1 diabetes and DR9-DQ3 in typical type 1A diabetes indicated high odds ratios (13.3 and 13.3, respectively). Conclusions/interpretation Our results suggest that class II HLA contributes to the development of fulminant type 1 diabetes. Susceptibility and resistance of the HLA subtype to type 1 diabetes are distinct between fulminant and typical autoimmune type 1 diabetes. An erratum to this article is available at .     

线粒体tRNALeu(UUR)基因点突变与1型糖尿病

目的　线粒体ｔ Ｒ Ｎ Ａ Ｌｅｕ（ Ｕ Ｕ Ｒ） 基因３２４３ 位点 Ａ→ Ｇ 突变是糖尿病的致病基因之一。本研究是为了了解该基因的突变在中国１ 型糖尿病患者中的情况以及与自身免疫导致１ 型糖尿病有无关联。方法　对１１６ 例随机收集的１ 型糖尿病患者用聚合酶链反应限制性内切酶消化作该点突变的筛选；８２ 例患者同时进行了谷氨酸脱羧酶（ Ｇ Ａ Ｄ） 抗体的测定。结果　发现１ 例该点突变（０ ．８６ ％ ） ，４８ 例 Ｇ Ａ Ｄ 抗体阳性（５８ ．５ ％ ） 。线粒体ｔ Ｒ Ｎ Ａ Ｌｅｕ（ Ｕ Ｕ Ｒ） 基因突变携带者 Ｇ Ａ Ｄ 抗体阴性，其家系成员糖尿病有不同的发病方式，但均表现为胰岛素缺乏。结论　线粒体ｔ Ｒ Ｎ Ａ Ｌｅｕ（ Ｕ Ｕ Ｒ） 基因异常所致糖尿病表现为胰岛素缺乏可能与自身免疫胰岛炎无关，而是一种独特的糖尿病亚型。     

Frequency of Hashimoto's thyroiditis in children with type 1 diabetes mellitus

A total of 1419 children with type 1 diabetes mellitus was investigated in order to assess the true frequency of Hashimoto's thyroiditis (HT), diagnosed by microsomal and/or thyroglobulin autoantibodies, by ultrasound and in many cases also by fine needle biopsy. According to these criteria, 55 cases (3.9%) of HT were identified, a number significantly higher (P<0.0001) than the distribution reported in the normal paediatric population. No typical antibody pattern was seen prior to the onset of HT, nor was an antibody threshold level found which could have been diagnostic for this disease. Patients with subclinical hypothyroidism were treated withl-thyroxine and were investigated regarding the behaviour of anti-thyroid autoantibodies; however, no significant changes were seen. The data showed a high frequency of HT in diabetic children, and therefore we recommend that children with type 1 diabetes mellitus should be screened for thyroid autoantibodies and those positive should undergo periodic thyroid function testing.A collaborative study of the AASGPED-Alpe Adria Study Group of Pediatric Endocrinology and Diabetology     

Exocrine pancreas functions in children with type 1 diabetes mellitus

Background and study aimWe evaluated exocrine pancreas functions using a noninvasive indicator in a case–control study conducted on children and adolescents diagnosed with type 1 diabetes mellitus.Patients and methodsSixty-seven patients who participated in a summer camp were enrolled in this study. Nineteen healthy children in the same age group were assigned to the control group. Fecal pancreatic elastase was assayed using the enzyme-linked immunosorbent assay technique. Values higher than 200 µg/g were considered an indication of sufficient exocrine pancreatic functioning, values between 100 µg/g and 200 µg/g were considered mild exocrine pancreatic insufficiency, and values below 100 µg/g were considered severe exocrine pancreatic insufficiency.ResultsThe mean concentration of fecal elastase was 158.38 ± 59.67 µg/g. The patients were assigned to three groups according to these values. Thirteen patients (22%) had sufficient fecal elastase levels, whereas 36 patients (62%) had mildly insufficient levels, and nine patients (16%) had severely insufficient fecal elastase concentrations. The levels of fecal elastase, amylase, lipase, and zinc were significantly different between the patients and controls (p < 0.001). Only the duration of diabetes was significantly different between patients with different severities of exocrine pancreatic insufficiency (p = 0.037). Additionally, the group with severe pancreatic insufficiency had more frequent hypoglycemic attacks.ConclusionExocrine pancreatic insufficiency may develop in children with diabetes, and hypoglycemia attacks are observed more frequently depending on the severity of pancreatic insufficiency.     

胰岛B细胞特异性锌转运蛋白与1型糖尿病

1型糖尿病（T1DM）是胰岛呈进行性破坏的自身免疫性疾病,以表达于胰岛B细胞的分子靶点作为抗原参与自身免疫反应为特征。其中阳离子外流锌转运蛋白8（ZnT8,SLC30A8）是人类T1DM的主要自身抗原之一,T1DM患者中SLC30A8基因位点上氨基酸325的多态性决定了其自身抗体多肽的特异性。ZnT8自身抗体可以在新发T1DM和糖尿病前期患者血清中检测出,在T1DM患者血清中其他自身抗体（谷氨酸脱羧酶抗体、抗酪氨酸磷酸酶抗体、抗胰岛素抗体和抗胰岛细胞抗体）阴性时ZnT8抗体仍有26％的阳性率。对自身抗体ZnT8的检测有助于在人群中筛查糖尿病前期患者,因此检测ZnT8抗体对评估T1DM的发生发展是必要的,ZnT8（SLC30A8）是T1DM的一个重要并独立的预测因子。     

巨噬细胞炎性蛋白-1与1型糖尿病

巨噬细胞炎性蛋白-1(MIP-1)是一种趋化因子,与受体结合后,可以发挥趋化和促进炎症的生物学作用,能引起多种炎症性疾病。研究表明,MIP-1α可以导致破坏性胰岛炎以及自发性1型糖尿病,而MIP-1β则对1型糖尿病起保护性作用。本文对MIP-1的结构、功能及其在1型糖尿病中的作用机制进行综述。     

小泛素相关修饰物与1型糖尿病

小泛素相关修饰物作为一个表达于全身多个器官的蛋白质家族,可对胞内多种转录因子、酶、蛋白质进行翻译后修饰.生理状态下,小泛素相关修饰物与胰岛β细胞的发育、成熟以及胰岛素的分泌密切相关.同时,它通过抑制机体自身免疫反应,减少胰岛β细胞凋亡而减缓1型糖尿病的发生、发展.对此家族蛋白及其修饰过程的深入研究为治疗1型糖尿病提供新的思路.     

天然免疫细胞在1型糖尿病中的作用

1型糖尿病（T1DM）是一种复杂的自身免疫性疾病,主要是由T、B细胞破坏胰岛β细胞所致.虽然病因不明,但最终一系列天然免疫细胞及特异性免疫细胞相互作用,导致胰岛β细胞损伤和T1DM的发生.对动物模型和T1DM患者的研究发现,单核/巨噬细胞、自然杀伤细胞、自然杀伤T细胞、树突状细胞和淋巴细胞相互作用可影响T1DM的发生、发展.因此,研究天然免疫细胞在T1DM发生、发展中的作用,可能为防治T1DM提供新的方向.     

Family history and risk of type 1 diabetes mellitus

The aim of the study was to evaluate association of type 1 diabetes in children and adolescents with positive family history of type 1 diabetes, type 2 diabetes, and thyroid, adrenal, rheumatic, allergic, celiac and some other diseases. A case-control study was conducted in Belgrade. The case group comprised 105 subjects ≤ 16 years old who were for the first time hospitalized because of type 1 diabetes during the period 1994–1997. For each case, two controls were chosen among children and adolescents treated for skin diseases. Cases and controls were individually matched by age (± one year), sex and place of residence (all were from Belgrade). In the statistical analyses we used χ²-test, Fisher's exact test and univariate and multivariate logistic regressions. According to multivariate logistic regression analysis, risk of type 1 diabetes was significantly associated with a positive family history for type 1 diabetes (OR=4.04; 95% CI, 2.31–7.07), allergic diseases (OR=3.32; 95% CI, 1.63–6.76), celiac and Crohn's diseases (OR=11.02; 95% CI, 1.14–106.89) and other diseases (thrombocytopenia, alopecia areata, psoriasis, chronic uveitis and pernicious anemia; OR=3.63; 95% CI, 1.05–12.48). Received: 10 August 2000 / Accepted in revised form: 15 April 2002     

Perturbation of hyaluronan metabolism predisposes patients with type 1 diabetes mellitus to atherosclerosis

Aims/hypothesis Cardiovascular disease contributes to mortality in type 1 diabetes mellitus, but the specific pathophysiological mechanisms remain to be established. We recently showed that the endothelial glycocalyx, a protective layer of proteoglycans covering the endothelium, is severely perturbed in type 1 diabetes, with concomitantly increased plasma levels of hyaluronan and hyaluronidase. In the present study, we evaluated the relationship between hyaluronan and hyaluronidase with carotid intima-media thickness (cIMT), an established surrogate marker for cardiovascular disease. Subjects and methods Non-smoking type 1 diabetes patients without micro- or macrovascular complications and matched controls were recruited and cIMT of both carotid arteries was measured. To evaluate the relationship between cIMT and hyaluronan and hyaluronidase as well as other parameters, uni- or multivariate regression analyses were performed. Results We included 99 type 1 diabetes patients (age 10–72 years) and 99 age- and sex-matched controls. Mean cIMT, HbA_1c, high sensitivity C-reactive protein, hyaluronan and hyaluronidase were significantly increased in type 1 diabetes vs controls. Plasma hyaluronan and hyaluronidase were correlated in type 1 diabetes. In univariate regression analyses, mean IMT was associated with plasma hyaluronan, age and male sex, whereas after multivariate analysis only age and sex remained statistically significant. Conclusions/interpretation We conclude that type 1 diabetes patients show structural changes of the arterial wall associated with increased hyaluronan metabolism. These data may lend further support to altered glycosaminoglycan metabolism in type 1 diabetes as a potential mechanism involved in accelerated atherogenesis.     

1型糖尿病的二级预防临床研究进展

1型糖尿病是一种器官特异性自身免疫性疾病,目前尚无根治方法,患者需要终身胰岛素替代治疗。将1型糖尿病防患于未然,是患者和医师的梦想。近年来,易感基因和胰岛自身抗体检测方面的进展为1型糖尿病前期的预测和预防提供了理论依据和技术可能。此外,1型糖尿病二级预防的免疫干预治疗也取得了一定的成效。现对1型糖尿病二级预防的最新研究...     

Gut microbiota dysbiosis in Chinese children with type 1 diabetes mellitus: An observational study

BACKGROUNDGut microbiota dysbiosis is reportedly actively involved in autoimmune diseases such as type 1 diabetes mellitus (T1DM). However, the alterations in the gut microbiota and their correlation with fasting blood glucose (FBG) in Chinese children with T1DM remain unclear. AIMTo investigate alterations in the gut microbiota in Chinese children with T1DM and their associations with clinical indicators.METHODSSamples from 51 children with T1DM and 47 age-matched and gender-matched healthy controls were obtained, to explore the structural and functional alterations in the fecal microbiota. The V3-V4 regions of the 16S rRNA gene were sequenced on a MiSeq instrument, and the association with FBG were analyzed. RESULTSWe found that the bacterial diversity was significantly increased in the T1DM-associated fecal microbiota, and changes in the microbial composition were observed at different taxonomic levels. The T1DM-reduced differential taxa, such as Bacteroides vulgatus ATCC8482, Bacteroides ovatus, Bacteroides xylanisolvens, and Flavonifractor plautii, were negatively correlated with FBG, while the T1DM-enriched taxa, such as Blautia, Eubacterium hallii group, Anaerostipes hadrus, and Dorea longicatena, were positively correlated with FBG. Bacteroides vulgatus ATCC8482, Bacteroides ovatus, the Eubacterium hallii group, and Anaerostipes hadrus, either alone or in combination, could be used as noninvasive diagnostic biomarkers to discriminate children with T1DM from healthy controls. In addition, the functional changes in the T1DM-associated fecal microbiota also suggest that these fecal microbes were associated with altered functions and metabolic activities, such as glycan biosynthesis and metabolism and lipid metabolism, which might play vital roles in the pathogenesis and development of T1DM. CONCLUSIONOur present comprehensive investigation of the T1DM-associated fecal microbiota provides novel insights into the pathogenesis of the disease and sheds light on the diagnosis and treatment of T1DM.     

Impaired stroke volume and aerobic capacity in female adolescents with type 1 and type 2 diabetes mellitus

AIM/HYPOTHESIS: This study was designed to determine whether type 2 diabetic adolescents have reduced aerobic capacity and to investigate the role of cardiac output and arteriovenous oxygen difference (a-vO(2)) in their exercise response. METHODS: Female adolescents (age 12-18 years) with type 2 diabetes mellitus (n = 8) and type 1 diabetes mellitus (n = 12) and obese (n = 10) and non-obese (n = 10) non-diabetic controls were recruited for this study. Baseline data included maximal aerobic capacity (cycle ergometer) and body composition. Cardiac output and a-vO(2) were determined at rest and during submaximal exercise. RESULTS: Diabetic groups had lower aerobic capacity than non-diabetic groups (p < 0.05). Adolescents with type 2 diabetes had lower aerobic capacity than the type 1 diabetic group. Maximal heart rate was lower in the type 2 diabetic group (p < 0.05). Exercise stroke volume was 30-40% lower at 100 and 120 beats per min in the diabetic than in the non-diabetic groups (p < 0.05). The a-vO(2) value was not different in any condition. CONCLUSIONS AND INTERPRETATION: Type 2 diabetic adolescents have reduced aerobic capacity and reduced heart rate response to maximal exercise. Furthermore, type 2 and type 1 diabetic adolescent girls have a blunted exercise stroke volume response compared with non-diabetic controls. Central rather than peripheral mechanisms contribute to the reduced aerobic capacity in diabetic adolescents. Although of short duration, type 2 diabetes in adolescence is already affecting cardiovascular function in adolescents.     

CXC趋化因子配体10与1型糖尿病

CXC趋化因子配体10(CXCL10)是一种重要的趋化因子,与受体结合后,可以发挥趋化和促进炎性反应的生物学作用,参与多种炎性反应性疾病的发生.研究表明,CXCL10及其受体在1型糖尿病(T1DM)患者中表达异常,其基因多态性可能与患T1 DM的风险性相关.CXCL10可导致破坏性胰岛炎以及T1 DM,其机制可能与病毒感染诱导CXCL10高表达,后者通过募集巨噬细胞及辅助性T细胞浸润胰岛以及抑制胰岛β细胞增殖有关.CXCL10及其受体拮抗剂在动物模型中的成功应用,有望成为治疗T1DM的新靶点.     

Anti-parietal cell antibodies and pernicious anemia in patients with type 1 diabetes mellitus and multiethnic background

Anti-parietal cell (APC) antibodies and pernicious anemia (PA) were evaluated in patients with type 1 diabetes (n = 75) and in controls. A higher frequency of APC (13.3%) and PA (4%) was found in cases than in controls (p = 0.003), associated with other autoimmune diseases (p = 0.003), but not with insulin or PTPN22 polymorphisms.     

Insulin degludec in Japanese patients with type 1 diabetes mellitus: A randomized controlled trial

Introduction

Insulin degludec is an ultra‐long‐acting insulin with a flat time‐action profile and duration of action >42 h. Data from several studies have shown insulin degludec to have a favorable therapeutic profile in type 1 and type 2 diabetes.

Materials and Methods

This was a 6‐week, parallel‐group, randomized controlled trial carried out in 65 Japanese patients with type 1 diabetes, previously treated with mealtime insulin aspart and either insulin glargine or neutral protamine Hagedorn insulin. Patients were randomized to receive either insulin degludec or insulin detemir, each once daily and at the same unit dose as pretrial basal insulin. During the trial, basal insulin was titrated according to a prespecified algorithm in order to achieve a fasting plasma glucose target of 80–109 mg/dL.

Results

No severe hypoglycemia occurred; there was no significant difference in confirmed hypoglycemia rates with insulin degludec and insulin detemir (rate ratio degludec/detemir 0.78; 95% confidence interval 0.45–1.34). The rate of nocturnal confirmed hypoglycemia was 69% lower with insulin degludec than with insulin detemir (rate ratio 0.31; 95% confidence interval 0.13–0.78). Final fasting plasma glucose levels were similar (insulin degludec 147 mg/dL, insulin detemir 136 mg/dL), despite differing baseline fasting plasma glucose levels.

Conclusions

In conclusion, no concerns relating to hypoglycemia or general safety were observed when initiating insulin degludec in Japanese patients with type 1 diabetes at the same unit dose as previous basal insulin. This trial was registered with ClinicalTrials.gov (no. NCT00841087).