Changes in longevity and causes of death among persons with hemophilia A

To examine recent changes in longevity and the causes of death among persons with hemophilia A, we evaluated death certificate data for persons who died in the United States from 1968 through 1989 and had hemophilia A or congenital Factor VIII disorder (ICD code 286.0) listed on the death certificate as one of the multiple causes of death. Multiple-cause-of-death mortality data for the United States from 1968 to 1989 were examined to compare death rates by year, focusing on death rates and causes of death for 1979-1981, 1983-1985, and 1987-1989. Gender, age group, race, geographic region, and median age at death of persons with hemophilia A and human immunodeficiency virus (HIV)-related disease listed as a cause of death were compared with those with hemophilia A without HIV-related disease. From 1968 through 1989, 2,792 hemophilia A deaths were reported. The death rate increased from 0.5 to 1.3 per 1,000,000 persons. From 1979-1981 through 1987-1989, mortality increased in all age groups above 9 years of age and age at death shifted markedly to lower ages. Median age at death decreased from 57 years in 1979-1981 to 40 years in 1987-1989. The percentage of deaths due to hemorrhage or diseases of the circulatory system decreased markedly as the result of the increase in deaths associated with HIV infection or infections other than HIV infection. Spread of HIV-1 infection in persons with hemophilia A has disrupted the reduction in mortality seen with factor replacement therapy, implementation of home care, and use of comprehensive hemophilia treatment centers. It is hoped that advances in the care of HIV-infected persons will improve survival in the hemophilia community. © 1994 Wiley-Liss, Inc.     

Main causes of death of patients with diabetes mellitus]

Among the causes of death in the patients with diabetes mellitus in Ukraine there prevailed cardiovascular disease (73.1 +/- 0.19%); malignant neoplasms ranked second (12.1 +/- 1.2%); tuberculosis constituted 1.6 +/- 1.2%, and all the rest of the diseases - 13.1 +/- +/- 1.2%, including coma - 0.5%. The frequency of death, particularly from cardiovascular diseases, is influenced by the patients' age, the severity and the duration of metabolic disturbances. The methods of treatment, particularly the saccharolytic sulphanilamide preparations, produce no effect on the death incidence.     

老年糖尿病死亡病例分析

目的了解老年糖尿病（DM）住院患者的死亡原因及其死亡危险因素。方法以预设表格方式对哈尔滨医科大学附属第二医院老年病房1993年1月1日至2006年12月31日期间住院的老年DM死亡病例进行回顾性调查。结果①老年DM住院患者死亡86例，占全部死亡病例的20．98％，其中以心血管疾病（33．72％）、脑血管疾病（17．44％）、呼吸系统疾病（13.95％）为前3位最主要死因。②在DM与非DM组的比较中，心血管疾病、脑血管疾病、呼吸系统疾病和泌尿系统疾病较非DM组显著增多，肿瘤患者在非DM组明显增多。③DM病程对高血压、心肌梗死、糖尿病肾病（DN）、脑梗死有显著影响。结论DM是增加老年心血管疾病、脑血管疾病、呼吸系统疾病、泌尿系统疾病的发生率和死亡率的一个重要因素。DM的病程增加也大大增加了高血压、心肌梗死、DN、脑梗死的发生率，从而显著增加了老年人的死亡风险。     

Mortality and causes of death in Italian persons with haemophilia, 1990–2007

Summary. Although a number of studies have analysed so far the causes of death and the life expectancy in haemophilic populations, no investigations have been conducted among Italian haemophilia centres. Thus, the aim of this study was to investigate mortality, causes of deaths, life expectancy and co‐morbidities in Italian persons with haemophilia (PWH). Data pertaining to a total of 443 PWH who died between 1980 and 2007 were retrospectively collected in the 30 centres who are members of the Italian Association of Haemophilia Centres that chose to participate. The mortality rate ratio standardized to the male Italian population (SMR) was reduced during the periods 1990–1999 and 2000–2007 such that during the latter, death rate overlapped that of the general population (SMR 1990–1999: 1.98 95% CI 1.54–2.51; SMR 2000–2007: 1.08 95% CI 0.83–1.40). Similarly, life expectancy in the whole haemophilic population increased in the same period (71.2 years in 2000–2007 vs. 64.0 in 1990–1999), approaching that of the general male population. While human immunodeficiency virus infection was the main cause of death (45%), 13% of deaths were caused by hepatitis C‐associated complications. The results of this retrospective study show that in Italian PWH improvements in the quality of treatment and global medical care provided by specialized haemophilia centres resulted in a significantly increased life expectancy.     

Type I diabetes mellitus

Summary The major genetic susceptibility to insulin dependent (Type 1) diabetes is determined by genes in the HLA chromosomal region. An increased relative risk for developing the disease is observed in subjects who are HLA A1, A2, B8, B18, B15, B40, CW3, Bf^s, DW3, DW4, DRW3, DRW4 positive. There is an additive relative risk in subjects who possess two high risk HLA B alleles which has an important influence on the prevalence of the disease in sibships and possibly on the concordance rate in diabetic identical twins. There is also suggestive evidence that particular combinations of high risk HLA B alleles are associated with increased or persistent antibody production which may reflect enhanced or differential susceptibility. Certain factors (e. g. HLA B7, DW2 and DRW2) are associated with a significantly reduced risk and may exert a protective mechanism in Type I diabetes, by linkage disequilibrium with genes which reduce immune responsiveness. The significant increases and decreases in respect of the HLA B antigens are probably secondary to the corresponding HLA D and DRW associations which reflect a stronger linkage disequilibrium between the genes which determine these specificities and the putative genes which control susceptibility. Initial damage to the beta cells probably occurs a considerable time before the onset of symptoms and theoretically modification of the immune response early in the disease process may reduce the rate of beta cell destruction.     

Type 2 diabetes risk in persons with dysglycemia: the Framingham Offspring Study

Aims

Detection of risk of type 2 diabetes mellitus (T2DM) among adults with dysglycemia.

Methods

We used a nested case-cohort prospective design to estimate risk of new diabetes (diabetes treatment or FPG ≥7.0 mmol/L) among 1004 Framingham Heart Study Offspring with baseline dysglycemia [fasting plasma glucose (FPG) 5.4-6.9 mmol/L and/or 2-h post glucose load level 7.8-11.0 mmol/L]. Using clinical characteristics previously shown to predict incident T2DM, we used logistic regression to estimate odds ratios (OR), p-values for predictors, and assessment of model discrimination.

Results

At the end of 7 years follow-up there were 118 incident T2DM cases. In a model that included age, sex, elevated blood pressure or blood pressure treatment, lipid-lowering treatment and elevated triglycerides, we found the following additional characteristics to be independently associated with new T2DM: parental history of diabetes (OR 2.28, p = 0.004); excess adiposity (BMI ≥ 30 kg/m² or waist circumference ≥101.6 cm) (OR 2.04, p = 0.0005), and low HDL-C [<1.0 (men) or <1.3 mmol/L (women)] (OR 2.77, p < 0.0001). The multivariable C-statistic for this model was 0.701, and with glycemic category information included, c = 0.751.

Conclusions

The key non-glycemic traits that predicted later T2DM in adults with dysglycemia were parental history of diabetes, excess adiposity and low HDL-C.     

Diabetes in the parents of children with Type I diabetes

Aims/hypothesis. Previous studies have reported an excess of Type II (non-insulin-dependent) diabetes mellitus in parents of children with Type I (insulin-dependent) diabetes mellitus. We set out to characterise the clinical and immunogenetic features of diabetes in parents of affected children, and to test the hypothesis that there is no excess of Type II diabetes within this population. Methods. Clinical details were collected from 3164 parents of 1641 children with Type I diabetes participating in the Bart's-Oxford study of childhood diabetes. Islet cell antibodies, antibodies to GAD and IA-2, and HLA class II genotype were determined in a subset of this group. Individuals were assigned a classification of Type I diabetes on the basis of clinical features and measurement of islet autoantibodies. Results. Of 184 parents with diabetes, 138 (75 %) were on insulin. At least one islet autoantibody was detected in 90 (59 %) of 152 parents tested, and of 116 who were HLA-typed, 23 (20 %) had the highest risk genotype HLA-DRB1^*03-DQA1*0501-DQB1^*0201 / DRB1*04-DQA1^*0301-DQB1*0302. Of 46 non-insulin-treated parents, 12 had islet autoantibodies. Of all parents, 141 (4.5 %) were therefore classified as having Type I diabetes, and 31 (0.98 %) as Type II diabetes; 12 could not be classified because of missing data or samples. Conclusion/interpretation. Autoimmune diabetes can present late and without immediate need for insulin treatment in parents of children with the disease. Previous studies have categorised this as Type II diabetes. Our study suggests that there is no excess of non-autoimmune diabetes in the families of children with Type I diabetes. [Diabetologia (2002) 45: ▪–▪] Received: 7 November 2001 and in revised form: 3 January 2002     

Understanding sleep in persons with diabetes

Restorative sleep is as essential for well-being as proper diet or exercise in persons with type 2 diabetes. However, sleep disorders such as insomnia, restless leg syndrome/periodic leg movements, and obstructive sleep apnea increase in prevalence with age and are very common in persons with type 2 diabetes. Disrupted sleep may result in weight gain, increased insulin resistance, and decreased daytime functioning. Although sleep disturbances have a major influence on health and quality of life, diagnosis and treatment can reduce their negative effects. Diabetes educators are pivotal in patient assessment, management, teaching, and collaborating with the primary health care provider to deliver holistic management of the patient with diabetes. This article will provide diabetes educators with various strategies for assessing sleep, including an easy 8-item questionnaire that can be used in the clinical setting. In addition, interventions to improve sleep hygiene that can be easily implemented by diabetes educators will be described.     

1型糖尿病与猝死览

发生在1型糖尿病年轻患者夜间猝死的事件,称为"睡眠死亡综合征(death in bed syndrome)[1]”,其病因未明.本文就目前所见的这种综合征的资料作一综述. 一、睡眠死亡综合征的背景 1991年Tattersall和Gill报道22例年轻的1型糖尿病患者发生猝死的事件,其共同特征是:晚上发生无法预测的猝死,患者于次日发现安静地死在床上[2].患者的年龄多在40岁以下,糖尿病病程从数月到25年不等,大部份患者平素看起来健康,血糖控制在正常水平且夜间常有低血糖发生的经历,尸检报告没有发现解剖学方面的异常.故首次将这种猝死称为"睡眠死亡综合征”.而早在1979年Tunbrige对50岁以下死亡的糖尿病患者进行研究时记录有16人死于低血糖,而其中7人有这种典型睡眠死亡综合征的特点.此外,1991年以来,斯堪的纳维亚半岛已经报道80例以上的病例,其临床特征与睡眠死亡综合征中描述的一样.尽管这种猝死普遍发生在年轻的1型糖尿病患者中,但其机制不明.有人认为与胰岛素应用有关,但Tattersall和Gill没有发现证据支持这个观点.所以他们提出一个与自主神经功能异常有关的假说来解释这类事件.这种异常可能易致特殊致死性的心率紊乱,而夜间低血糖加重这种心率紊乱.     

Redistribution of blood volume in Type I diabetes

Aims/hypothesis. Impaired activity of endothelium-derived nitric oxide in Type I (insulin-dependent) diabetes mellitus will cause an increased vascular tone. Considering the lower production of nitric oxide in veins than in arteries, an impaired activity would have less vasoconstrictive effect in veins. The reported minimally changed total plasma volume in diabetes might, therefore, indicate a redistribution of blood volumes from the arterial to the venous side of the circulation. This could be more pronounced in patients with microalbuminuria. Methods. In 16 normoalbuminuric and 16 microalbuminuric Type I diabetic patients and 16 individually matched healthy control subjects, venous and arterial blood volumes, venous myogenic response and arterial distensibilities were assessed in the upper arm using an electrical bio-impedance method. Results. In diabetic patients, the venous blood volume and venous myogenic response were increased (p < 0.02 and p < 0.05, respectively), whereas the arterial blood volume did not change. Moreover, in diabetic patients the distensibility of the large arteries was decreased (p < 0.05) but increased in the total arterial bed (p < 0.05). Therefore, the distensibility of the small arteries must have been increased. No differences were found between normoalbuminuric and microalbuminuric diabetic patients. Conclusion/interpretation. The increase in venous blood volume and myogenic response and the decrease in distensibility of the large arteries in the upper arm are in agreement with the expected shift towards venous blood volume distribution in Type I diabetes with and without microalbuminuria. Furthermore, they support the haemodynamic hypothesis of the pathogenesis of diabetic microangiopathy. [Diabetologia (2001) 44: 429–432] Received: 11 September 2000 and in revised form: 27 November 2000     

Excess risk of diabetes in persons with hypertension

ProblemPersons with hypertension appear to be at increased risk of diabetes, an important predictor of cardiovascular disease. Whether, and to what extent, this risk may vary across subgroups defined on the basis of important clinical characteristics has not been well characterized.MethodsStudy population included members of Kaiser Permanente Northwest Region, a large health maintenance organization, aged ≥35 years and free of diabetes in 1998. Persons in the study population were stratified based on whether or not they had hypertension, and onset of diabetes was ascertained over a 6-year period beginning January 1999. Excess risk of diabetes was characterized in terms of risk differences between persons with and without hypertension, and was estimated on an overall basis and for subgroups defined on the basis of age, sex, and body mass index (BMI).ResultsStudy population totaled 104,368; 44% had hypertension. Relative risk (RR) of developing diabetes was 2.7 (95% CI: 2.6–2.8) for those with vs. without hypertension [21.0 (95% CI: 20.7–21.4) vs. 7.8 (95% CI: 7.6–8.0) per 1000 person-years, respectively]. Adjusted for age, sex, and BMI, RR of diabetes was 1.8 (95% CI: 1.7–1.9). With one exception (men, aged ≥75 years), risk of diabetes was higher across all age and BMI strata for both men and women with vs. without hypertension; differences in risk were greatest among those with high BMI (≥35 kg/m²). Across BMI strata, RR of developing diabetes was generally higher at younger ages.ConclusionAll persons with hypertension, irrespective of age, sex, and BMI, are at elevated risk of developing diabetes. Men and women with hypertension who are overweight or obese are at substantially elevated risk of diabetes, regardless of age, and should be monitored especially closely for the development of this disease.     

The aetiology of Type I diabetes.

The aetiology of Type I diabetes involves both genetic and environmental factors. The genes implicated are 'susceptibility genes', which modify risk. Individual susceptibility genes may not be required and are not sufficient for disease development. The strongest genetic risk component is encoded within the major histocompatibility complex (MHC) and is designated IDDM I. The HLA-DQ genes contribute to the risk, but so may other MHC-encoded genes. The susceptibility encoded by IDDM2 refers to a variable number of tandem repeats in the insulin gene region. Many other genomic regions have been designated as susceptibility intervals potentially containing candidate genes. Environmental factors appear to be important in disease expression in either a causative or a protective role. Epidemiological data indicate that such factors operate from early in life. Viral infection(s) may have a disease-initiating and/ or accelerating effect. A potential diabetogenic role for cows' milk protein remains unconfirmed. Further research is necessary to elucidate fully the aetiological factors involved and how they interact.