A clinical screening tool identifies autoimmune diabetes in adults

OBJECTIVE: Latent autoimmune diabetes in adults (LADA) is defined as adult-onset diabetes with circulating islet antibodies but not requiring insulin therapy initially. Diagnosing LADA has treatment implications because of the high risk of progression to insulin dependency. Currently, there are no recommendations for islet antibody testing in adult-onset diabetes. In this study, we aimed to develop a clinical screening tool to identify adults at high risk of LADA who require islet antibody testing. RESEARCH DESIGN AND METHODS: Subjects with LADA (n = 102, GAD antibody [GADA]+) and type 2 diabetes (n = 111, GADA-) (aged 30-75 years) were interviewed retrospectively. The clinical features documented were age of onset, acute symptoms of hyperglycemia, BMI, and personal and family history of autoimmune disease. Any clinical feature that was significantly more frequent in LADA was designated as a distinguishing clinical feature. In each subject, a "LADA clinical risk score," based on the total number of distinguishing features, was calculated. A prospective study of adults with newly diagnosed diabetes (n = 130) was used to determine whether the LADA clinical risk score could identify LADA. RESULTS: In the retrospective study, five clinical features were more frequent in LADA compared with type 2 diabetes at diagnosis: 1) age of onset <50 years (P < 0.0001), 2) acute symptoms (P < 0.0001), 3) BMI <25 kg/m2 (P = 0.0004), 4) personal history of autoimmune disease (P = 0.011), and 5) family history of autoimmune disease (P = 0.024). In the prospective study, the presence of at least two of these distinguishing clinical features (LADA clinical risk score > or =2) had a 90% sensitivity and 71% specificity for identifying LADA and a negative predictive value for a LADA clinical risk score < or =1 of 99%. CONCLUSIONS: At least two distinguishing clinical features are found in a majority of patients with LADA at diagnosis and can be used to identify adults with diabetes at higher risk for LADA.     

A Case Report of LADA in the Primary Care Setting

Latent autoimmune diabetes in adults (LADA), a slowly progressing form of autoimmune diabetes, accounts for 2%–12% of all diabetes. Pancreatic beta cell function eventually deteriorates, rendering the patient insulin dependent and at risk for serious complications. All newly presenting adult persons with diabetes should be screened for LADA. In particular, consider LADA in those adults with a personal or family history of autoimmune conditions or those persons diagnosed with type 2 diabetes initially controlled on evidence-based therapies but then become difficult to manage and exhibit signs, such as unintended weight loss, that are more typical of persons with type 1 diabetes.     

成人隐匿性自身免疫糖尿病与2型糖尿病的血管并发症比较

目的 探讨成人隐匿性自身免疫糖尿病(LADA)与2型糖尿病(T2DM)血管并发症(包括微血管病变及相关大血管疾病)的差异.方法 比较203例LADA患者与年龄、性别、糖尿病病程及糖尿病家族史匹配的T2DM患者24 h尿白蛋白、眼底检查或荧光造影、心电图、肌电图、血压、血脂、体质指数、空腹血糖、餐后2h血糖、糖化血红蛋白、C肽等方面的差异.结果 ①微血管病变:LADA患者较T2DM患者糖尿病肾病的患病率高(39.9%vs.28.6%,P＜0.05),而2组间视网膜病变和周围神经病变的患病率差异无统计学意义(P＞0.05).②大血管病变:LADA患者较T2DM患者高血压、代谢综合征的患病率低(38.9%vs.55.7%,P＜0.01;33.0%vs.45.3%,P＜0.01),2组间冠心病及脑梗死的患病率差异无统计学意义(均P＞0.05).结论LADA患者与T2DM患者血管并发症存在差异:LADA患者糖尿病肾病患病率较高,而高血压和代谢综合征的患病率较低.     

Dominant Western health care: type 2 diabetes mellitus.

Diabetes is a major public health problem with serious complications. In 2002, the Centers for Disease Control estimated that 18.2 million people in the United States had diabetes. One in every 400 to 500 adolescents is diagnosed with type 1 diabetes mellitus (T1DM), and pediatric type 2 diabetes mellitus (T2DM) represents an emerging public health concern. The Children's Hospital of Philadelphia (CHOP) identified 337 children with T2DM through 2004. These children were mostly female and obese with a strong family history of T2DM. One patient's course of treatment for 1.5 years after initial presentation is described. Nineteen percent of the patients at CHOP were diagnosed with a neuropsychiatric illness before T2DM onset, further complicating their treatment. There is an imperative need for large-scale studies investigating the pathophysiology, treatment, and complications of T2DM in adolescents and youth.     

胰岛自身抗体联合生化指标检测在成人隐匿性糖尿病诊断中的临床意义

目的 通过对血清谷氨酸脱羧酶抗体(GAD)、胰岛细胞抗体(ICA)、血糖、糖化血红蛋白(HbAlc)的联合检测,探讨临床诊断为2型糖尿病(T2DM)患者中发现成人隐匿性自身免疫性糖尿病(LADA)的意义和诊断价值.方法 测定349例T2DM患者的血清GAD、ICA、C肽、血糖及HbAlc,检测出其中的LADA患者,并与T2DM患者的各项指标进行比较分析.结果 349例T2DM患者中共确诊为LADA患者27例(7.74％).LADA患者空腹C肽及餐后2hC肽分别为(0.31±0.21)、(0.90±0.22)μg/L,较T2DM患者的空腹C肽(1.23±0.85)μg/L和餐后2hC肽(3.45±2.96)μg/L明显降低,差异有统计学意义(P＜0.05).LADA患者空腹血糖及HbAlc分别为(12.15±25.01 )mmol/L、(10.12±2.78)％,较T2DM患者的(9.45±13.07)mmol/L、(8.04±2.95)％明显升高,差异有统计学意义(P＜0.05).结论 各项指标联合胰岛β细胞自身抗体检测可提高LADA患者的检出率,有助于LADA的早期诊断.     

Characterization of the MODY3 phenotype. Early-onset diabetes caused by an insulin secretion defect.

Maturity-onset diabetes of the young (MODY) type 3 is a dominantly inherited form of diabetes, which is often misdiagnosed as non-insulin-dependent diabetes mellitus (NIDDM) or insulin-dependent diabetes mellitus (IDDM). Phenotypic analysis of members from four large Finnish MODY3 kindreds (linked to chromosome 12q with a maximum lod score of 15) revealed a severe impairment in insulin secretion, which was present also in those normoglycemic family members who had inherited the MODY3 gene. In contrast to patients with NIDDM, MODY3 patients did not show any features of the insulin resistance syndrome. They could be discriminated from patients with IDDM by lack of glutamic acid decarboxylase antibodies (GAD-Ab). Taken together with our recent findings of linkage between this region on chromosome 12 and an insulin-deficient form of NIDDM (NIDDM2), the data suggest that mutations at the MODY3/NIDDM2 gene(s) result in a reduced insulin secretory response, that subsequently progresses to diabetes and underlines the importance of subphenotypic classification in studies of diabetes.     

Mechanisms in the development of type 2 diabetes mellitus.

The leading cause of death among patients with type 2 diabetes mellitus (DM) is cardiovascular disease, with 75% of these deaths attributed to coronary heart disease. Over the previous two decades the pathophysiological basis of type 2 DM has been extensively investigated. Although many of the underlying molecular mechanisms involved in the development of this disorder remain to be explained, it is clear that type 2 DM is a complex medical disorder characterized by insulin resistance and defects in insulin secretion. The process through which the metabolic derangements of type 2 DM accelerate the development of cardiovascular disease in type 2 DM has yet to be determined and remains an area of intense investigation, focusing on hyperglycemia and insulin resistance as major underlying contributors. This article explores current information related to the pathophysiology of type 2 DM alone and its relationship to the development to cardiovascular disease.     

Latent Autoimmune Diabetes in Adults

Latent autoimmune diabetes in adults (LADA) is a genetically linked, autoimmune form of type 1 diabetes mellitus that is commonly seen after age 30 in patients who often have a normal body mass index without overt signs of metabolic syndrome. They have positive circulating antibodies reflecting the autoimmune nature of beta cell destruction, and they frequently are poorly controlled on oral anti-diabetic agents. Because they are older when first symptomatic, they are often diagnosed with type 2 diabetes. However, it is important to recognize patients with LADA because they often progress quickly to insulin dependence. The characteristics of LADA, pathogenesis, diagnostic work-up, complications, and evidence-based management of the disease will be reviewed. Implications for practice will be included.     

Overcoming psychological barriers to insulin use in type 2 diabetes

Type 2 diabetes mellitus (DM) is characterized by a gradual decrease in insulin sensitivity in peripheral tissues and the liver (insulin resistance), followed by a gradual decline in beta-cell function and insulin secretion. Given this decline, many patients with type 2 DM will require insulin therapy to achieve the glycemic target recommended by the American Diabetes Association of glycosylated hemoglobin (A1C) <7%. The combination of insulin plus oral antidiabetic drugs (OADs) has been shown to improve A1C values in patients who were not adequately controlled with OADs alone. Despite its established benefits, however, insulin therapy continues to be underused. The reluctance to initiate insulin therapy is often related to both provider and patient misperceptions about insulin's efficacy and side effects, as well as the perceived complexity of the treatment regimen. In addition, insulin therapy may be viewed as a "last resort" treatment option for severe disease or as "punishment" for patients' failure to manage their disease. However, patients should be made aware from the time of diagnosis that diabetes is a progressive disease and that it is likely that insulin therapy will be required at some point during the course of the disease. The subject of insulin therapy, therefore, should be approached positively and should be presented as an effective and flexible way to achieve glycemic goals for any patient at any time during therapy.     

2型糖尿病家系一级亲属脂代谢紊乱和胰岛素抵抗变化的研究

目的　探讨 2型糖尿病家系一级亲属非糖尿病同胞脂代谢紊乱和胰岛素抵抗的情况。方法　检测了 5 2例 2型糖尿病家系一级亲属非糖尿病同胞 (FDR)和 19例正常对照组的体重指数、腰围、臀围、腰臀比、血压、血糖、血脂和胰岛素水平。采用稳态模式 (HOMA IR)评价胰岛素抵抗。结果　FDR组的腰围 (W )、臀围 (H)、体重指数(BMI)、空腹胰岛素 (FINS)和HOMA IR明显高于对照组 (P <0 .0 1)。多元逐步回归分析显示 ,空腹血糖 (FBG)、BMI和家族史是影响 2型糖尿病家系一级亲属非糖尿病同胞胰岛素抵抗主要的危险因素。结论　 2型糖尿病家系一级亲属非糖尿病同胞在未发生糖尿病时已存在高胰岛素血症和胰岛素抵抗 ,并且可能与遗传有关     

Behavior and biology: the prevention of type 2 diabetes

Type 2 diabetes mellitus (DM), characterized by insulin resistance and a beta-cell secretory defect, appears to result from a number of gene and environmental interactions. There are marked differences in the phenotypic expression of type 2 DM with individuals exhibiting varying levels of insulin resistance and impairments in insulin secretion. Study results indicate that a number of healthy lifestyle behaviors, such as increased physical activity and reduced intake of dietary fat, are associated with decreased development of type 2 DM. This article explores the genetic and environmental factors associated with the development of type 2 DM along with the role of lifestyle modifications in the prevention of this disease.     

Lipid reducing and antioxidant action of mexicor in patients with diabetes mellitus type 2

AIM: To study mexicor effects on functional activity of beta-cells, insulin resistance, lipid metabolism and lipid peroxidation in patients with diabetes mellitus (DM) type 2. MATERIAL AND METHODS: Twenty patients with DM type 2 participated in a double blind randomized trial of mexicor vs placebo. Before and after therapy the following parameters were studied: plasma glucose before meal, immunoreactive insulin, glycosilated hemoglobin, cholesterol, triglycerides, LDLP and HDLP cholesterol, malonic dialdehyde, dienic conjugates, superoxide dismutase, catalase, glutathione peroxidase and alpha-tocopherol. RESULTS: Mexicor significantly improved compensation of carbohydrate metabolism by glucose and glycosylated hemoglobin in the blood, insulin resistance value, lipid metabolism and lipid peroxidation in activation of antioxidant enzymes. CONCLUSION: Mexicor in therapy of DM type 2 improves carbohydrate and lipid metabolism, lipid peroxidation, activates antioxidant defence enzymes, functional activity of beta-cells, reduces insulin resistance.     

胰岛素抵抗的2型糖尿病人群的血脂分析

目的：探讨胰岛素抵抗的2型糖尿病（T2DM）人群血脂与对照组、2型糖尿病非胰岛素抵抗组的。方法：分别测定159例2型糖尿病患者及132例健康人群（CON组）空腹血糖、空腹胰岛素、三酰甘油、高密度脂蛋白-胆固醇、低密度脂蛋白-胆固醇和胆固醇,并计算胰岛素抵抗指数（IR）。结果：（1）CON组与胰岛素抵抗的T2DM组比较,两间FBG、FIN、IRI、TG、HDL、LDL差异有统计学意义（P〈0.05）;（2） CON组与非胰岛素抵抗的T2DM组比较,两组间FBG、CHOL、HDL差异有统计学意义（P〈0.05）;（3）胰岛素抵抗的T2DM组与非胰岛素抵抗的T2DM组比较,两组间FBG 、FIN、 IRI、TG、CHOL差异有统计学意义（P〈0.05）。（4） IR与FBG、FIN、TG、HDL有显著相关性。结论：2型糖尿病患者的脂代谢与胰岛素抵抗密切相关,推测有胰岛素抵抗的2型糖尿病患者容易发生血脂紊乱。     

Diagnosis and management of type 2 diabetes and prediabetes

Treatment of type 2 diabetes mellitus (T2DM), a progressive disease, requires early and appropriate therapies, with frequent monitoring and reassessment to make certain goals are attained. Chronic hyperglycemia can cause macrovascular and microvascular complications, many of which may be apparent on initial diagnosis. As beta-cell function deteriorates and insulin resistance intensifies, patients find that oral pharmacologic therapy is becoming less effective at minimizing the effects of chronic hyperglycemia. Eventually, most will require exogenous insulin therapy. Primary care physicians manage over 90% of T2DM patients, so we must have a better understanding of our roles as patient educators, advocates, and medical providers, and do everything in our power to help our patients achieve the lowest and safest glycated hemoglobin (A1C) possible.     

2型糖尿病胰岛素抵抗与缺血性脑卒中关系的初步探讨

目的　探讨胰岛素抵抗对 2型糖尿病缺血性脑卒中的可能发病机制。方法　将 194例 2型糖尿病患者分为缺血性脑卒中组 6 3例 ,无脑卒中组 131例 ,两组患者进行血压、血糖、血脂、糖化血红蛋白 (HbA1c)、胰岛素 (INS)及胰岛素敏感性 (ISI)等差异性比较。结果　两组间ISI、HbA1c、总胆固醇 (TC)差异有统计学意义 (P <0 .0 1) ,体重指数 (BMI)、空腹胰岛素 (FINS)、空腹血糖 (FBG) /FINS和高密度脂蛋白 胆固醇 (HDL C)差异亦有统计学意义 (P <0 .0 5 ) ;两组间糖耐量试验各时相血糖值比较差异均无统计学意义 (P >0 .0 5 ) ,而脑卒中组各时相INS均较无脑卒中组明显升高 (P <0 .0 5或 P <0 .0 1) ,尚可见两组INS峰值后移。结论　 2型糖尿病除了糖脂代谢紊乱外 ,胰岛素抵抗和代偿性高胰岛素血症可能是缺血性脑卒中的又一危险因素     

Low incidence of vascular complications in patients with diabetes mellitus associated with liver cirrhosis as compared with type 2 diabetes mellitus

We compared clinical features and vascular complications of patients with diabetes mellitus associated with liver cirrhosis versus patients with type 2 diabetes mellitus. Subjects were 19 patients (LC-DM group) in whom diabetes was diagnosed after development of liver cirrhosis. Control consisted of 38 patients with type 2 diabetes (T2DM group) matched for sex, age, duration of diabetes, body mass index, treatment, and degree of glycemic control, which was determined by glycoalbumin. The LC-DM group had significantly more smokers, higher serum insulin levels, more insulin resistance calculated by homeostasis model assessment, lower blood counts (white and red blood cells, hemoglobin, and platelets), and lower serum levels of total cholesterol, triglyceride, low density lipoprotein cholesterol and lipoprotein (Lp)(a) than the T2DM group. The incidence of diabetic retinopathy and cerebrovascular disease was significantly lower in the LC-DM group compared to the T2DM group. Logistic regression analysis indicated that Lp(a) and the diabetes duration were significant predictors for the retinopathy, while Lp(a) was a significant predictor for the cerebrovascular complication. In diabetes associated with liver cirrhosis, the incidence of diabetic retinopathy and cerebrovascular disease is lower than in type 2 diabetes mellitus in this study, probably because of lower levels of serum Lp(a).     

Variable number of tandem repeats of the insulin gene determines susceptibility to latent autoimmune diabetes in adults.

BACKGROUND: The different clinical presentations of latent autoimmune diabetes in adults (LADA) and type 1 diabetes mellitus may be the result of susceptibility genes in determining the mode of onset. We analyzed the 5' polymorphisms of the insulin mini-satellite region (INS), a variable number of tandem repeats (VNTR) [repeat units; RU]. We evaluated the association of the different INS-VNTR alleles in patient susceptibility to LADA autoimmune diabetes. To our knowledge, this constitutes the first study of this kind performed in a Caucasian population. METHODS: From an group of 160 Argentinean patients previously characterized as having LADA, we selected 44 patients who presented with humoral autoimmunity for genotyping and compared them to 88 patients with type 1 diabetes and 138 healthy individuals. The INS-VNTR allele classes were determined by Southern blotting (class I: 21-44RU; class III: 138-159RU). Subjects with class I alleles were further studied using PCR amplification to determine the exact length of the alleles (short 1S: 22-37RU; medium 1M: 38-41RU; large 1L: 42-43RU). Allelic and genotype frequencies were estimated by chi(2) tests for independence with 2 x 2 contingency tables and the relative risks (RR) were determined using GraphPad InStat software. RESULTS: We observed differential associations among the class I alleles when comparing patients with LADA (80.6%) and type 1 diabetes (81.3%) with the controls (70%; p < 0.005). This increase was largely due to the high frequency of the 1S/S genotype (63.6% LADA vs 37% controls, with a p-value of 0.0019 [p1]; 53.4% type 1 diabetes vs 37% controls, with a p-value of 0.0149 [p2]). Remarkably, all LADA patients genotyped as class I homozygous had the shorter (S) class I allele (100%). Differences in the overall 1S distribution were observed: in LADA the 94.4% of the alleles were equal to or smaller than 35RU, while in patients with type 1 diabetes it was 78.3% and in controls 74.1%. Moreover, the relative risks associated with the 1S/S genotype for patients with LADA showed a substantial increase with respect to those with type 1 diabetes (52%) when we compare them to the controls (1S/S LADA/control, 2.282 [RR1] vs type 1 diabetes/control, 1.497 [RR2]). CONCLUSION: The presence of the 1S allele could be considered a risk factor in LADA patients, as previously reported for type 1 diabetes. The class I INS-VNTR allele in LADA increases genetic susceptibility to disease development.     

Parental diabetes in Taiwanese diabetic women with and without previous gestational diabetes

Background    Gestational diabetes mellitus (GDM) is reported to be associated with maternal but not paternal diabetes. This study examined the relative contribution of maternal and paternal diabetes among type 2 diabetic women with and without a GDM history.
Materials and methods    A total of 48 502 type 2 diabetic women from a national sample were interviewed by telephone. Among them, 510 reported a GDM history. Parental diabetes was compared between patients with and without a GDM history considering the confounding effects of age, body mass index, smoking, hypertension, duration of diabetes and insulin use.
Results    Patients with a GDM history were younger in age, had younger age of onset, longer duration of diabetes, slightly lower body mass index, higher prevalence of insulin use and lower prevalence of hypertension, but smoking rates were similar. The percentages of parental diabetes of nil, mother only, father only and both father and mother for those without a GDM history were 76·2, 15·2, 5·8 and 2·8%, respectively; and were 47·8, 26·8, 17·5 and 7·9%, respectively, for those with a GDM history ( P  < 0·001). The adjusted odds ratios for patients with versus without a GDM history for parental diabetes of nil, mother only, father only, and both father and mother were 1·000, 1·210 (0·948–1·544), 1·783 (1·341–2·371) and 2·094 (1·440–3·045), respectively.
Conclusions    Although maternal diabetes is more commonly seen, the disproportionately higher paternal diabetes in patients with a GDM history suggests an important role for paternal diabetes on the development of GDM into type 2 diabetes mellitus.     

PC-1基因K121Q变异与2型糖尿病的关系

目的探讨浆细胞膜糖蛋白(PC1)基因4号外显子K121Q多态性与2型糖尿病及临床特征的相关性。方法用聚合酶链反应限制性内切酶片段长度多态性分析(PCR RFLP)、DNA测序等技术检测上海地区汉族人群中165例2型糖尿病患者和98名正常糖耐量对照者PC1基因K121Q的多态性分布情况,同时采用PCR单链构像多态性分析(PCR SSCP)筛查该区域其他可能与2型糖尿病发生有关的多态性位点。结果糖尿病患者中KK基因型143例(86.67%),KQ基因型22例(13.33%),QQ基因型0例(0.00%),K、Q等位基因频率分别为93.33%和6.67%;正常对照组中KK基因型85例(86.73%),KQ基因型12例(12.25%),QQ基因型1例(1.02%),K、Q等位基因频率分别为92.86%和7.14%,2组人群的基因型和等位基因频率差异无显著性(P>0.05);2型糖尿病患者中Q等位基因携带者的胰岛素抵抗指数(IR)、血糖、胰岛素、血脂等均略高于KK基因型的患者,但两者之间的差异均无显著性;中国上海地区汉族人群Q等位基因频率明显低于欧洲白种人。结论目前尚不能确定PC1基因K121Q多态性与上海地区汉族人群胰岛素抵抗及2型糖尿病发病相关;PC1基因的K121Q多态性具有明显的种族差异。     

Managing older adults with diabetes

PURPOSE: To review special considerations in the management of adults 65 years of age and older with diabetes mellitus (DM) with particular attention to initiation of insulin in the management of type 2 DM (DM2), Medicare eligibility for insulin pump therapy, and intensive insulin therapy in both type 1 DM (DM1) and DM2 in older adults. DATA SOURCES: American Diabetes Association Standards of Medical Care in Diabetes, selected research articles, textbooks, and Internet sources. CONCLUSIONS: American Diabetes Association, American Association of Diabetes Educators, and American Association of Clinical Endocrinologist acknowledge that no long-term studies have been conducted in older adults with DM. Furthermore, these groups as well as the American Geriatric Society conclude that a person's functional capacity and not age should determine the treatment modality most beneficial in each situation. IMPLICATIONS FOR PRACTICE: Management of diabetes in the older adult is a common clinical scenario for primary care providers (PCPs). Treatment strategies follow a continuum over time from lifestyle modification to intensive management. Intensive insulin therapy, through the use of either multiple daily injections or continuous subcutaneous insulin infusion using insulin pumps, has demonstrated benefit in both DM1 and DM2; however, there is evidence that PCPs are reluctant to initiate insulin. Moreover, in the management of older adults with diabetes, evidence-based outcomes regarding intensive management are lacking. Further studies are needed.