Increasing incidence and age at diagnosis among children with type 1 diabetes mellitus over a 20-year period in Auckland (New Zealand)

Background

We aimed to evaluate the incidence of type 1 diabetes mellitus in children <15 years of age (yr) in the Auckland region (New Zealand) over 20 years (1990–2009).

Methods

We performed a retrospective review of all patients <15 yr diagnosed with type 1 diabetes, from an unselected complete regional cohort.

Results

There were 884 new cases of type 1 diabetes, and age at diagnosis rose from 7.6 yr in 1990/1 to 8.9 yr in 2008/9 (r² = 0.31, p = 0.009). There was a progressive increase in type 1 diabetes incidence among children <15 yr (p<0.0001), reaching 22.5 per 100,000 in 2009. However, the rise in incidence did not occur evenly among age groups, being 2.5-fold higher in older children (10–14 yr) than in the youngest group (0–4 yr). The incidence of new cases of type 1 diabetes was highest in New Zealand Europeans throughout the study period in all age groups (p<0.0001), but the rate of increase was similar in New Zealand Europeans and Non-Europeans. Type 1 diabetes incidence and average annual increase were similar in both sexes. There was no change in BMI SDS shortly after diagnosis, and no association between BMI SDS and age at diagnosis.

Conclusions

There has been a steady increase in type 1 diabetes incidence among children <15 yr in Auckland over 20 years. Contrary to other studies, age at diagnosis has increased and the greatest rise in incidence occurred in children 10–14 yr. There was little change in BMI SDS in this population, providing no support for the ‘accelerator hypothesis’.     

Evidence for an environmental effect in the aetiology of insulin dependent diabetes in a transmigratory population.

OBJECTIVE--To examine whether children of families moving from an area of low incidence of childhood diabetes to one which is higher show a corresponding rise in disease incidence. DESIGN--Disease incidence study over 12 years. SETTING--Bradford District Metropolitan Council area. SUBJECTS--All subjects aged 0-16 years resident within the study area. MAIN OUTCOME MEASURES--The incidences of childhood diabetes in Asian and non-Asian families. RESULTS--The incidence of diabetes in Asian children increased from 3.1/100,000 per year in 1978-81 to 11.7/100,000 per year in 1988-90 (chi 2 for trend = 4.95, df = 1, p = 0.026) whereas that for other children remained constant at 10.5/100,000 per year. Over the entire study period rates were lower in Asian females (4.9/100,000 per year) than in Asian males (8.8/100,000 per year) whereas the reverse was true for other children (males 9.2/100,000 per year; females 12.0/100,000 per year) (test for common odds ratio: chi 2 = 3.81, df = 1, p = 0.052). CONCLUSIONS--Offspring of this transmigratory population had a rising incidence of childhood diabetes which was approaching that of the indigenous population. The data provide strong evidence for an environmental effect in the aetiology of insulin dependent diabetes.     

Maternal and paternal age at delivery, birth order, and risk of childhood onset type 1 diabetes: population based cohort study

ObjectiveTo estimate the associations of maternal and paternal age at delivery and of birth order with the risk of childhood onset type 1 diabetes.DesignCohort study by record linkage of the medical birth registry and the national childhood diabetes registry in Norway.SettingNorway.SubjectsAll live births in Norway between 1974 and 1998 (1.4 million people) were followed for a maximum of 15 years, contributing 8.2 million person years of observation during 1989-98. 1824 cases of type 1 diabetes diagnosed between 1989 and 1998 were identified.ResultsThere was no association between maternal age at delivery and type 1 diabetes among firstborn children, but among fourthborn children there was a 43.2% increase in incidence of diabetes for each five year increase in maternal age (95% confidence interval 6.4% to 92.6%). Each increase in birth order was associated with a 17.9% reduction in incidence (3.2% to 30.4%) when maternal age was 20-24 years, but the association was weaker when maternal age was 30 years or more. Paternal age was not associated with type 1 diabetes after maternal age was adjusted for.ConclusionsIntrauterine factors and early life environment may influence the risk of type 1 diabetes. The relation of maternal age and birth order to risk of type 1 diabetes is complex.

What is already known on this topic

Maternal age at birth is positively associated with risk of childhood onset type 1 diabetesStudies of the effect of birth order on risk of type 1 diabetes have given inconsistent results

What does this study add?

In a national cohort, risk of diabetes in firstborn children was not associated with maternal ageIncreasing maternal age was a risk factor in children born second or laterThe strength of the association increased with increasing birth order     

Childhood Overweight Status Predicts Diabetes at Age 21 Years: A Follow‐up Study

We examined the prospective association of childhood BMI z‐score and BMI categories (normal or overweight) with young adult diabetes, controlling for early life, childhood, and adolescence factors. A subsample of 2,639 young adults from the Mater–University study of pregnancy (MUSP) and its outcomes, a prospective birth cohort who were born in Brisbane, Australia and for whom we had measured height and weight at 5 years and self‐reported diabetes at age 21 years. The risk of developing diabetes by age 21 years was greater among young adults who had greater BMI z‐score or were overweight at age 5 years than those who had normal BMI at age 5 years. Young adults who were overweight at age 5 years had an increased odds ratio of 2.60 (95% confidence interval (CI): 1.29, 5.22, in age‐ and sex‐adjusted model) of experiencing diabetes by age 21 years. Adjustment for potential confounders and mediators including intrauterine environmental factors, childhood dietary patterns, television watching, participation in sports and exercise, and current weight, did not substantively alter these associations. Overweight and increasing BMI z‐score at childhood is an independent predictor of young adult's type 1 and type 2 diabetes. Findings of this study suggest that childhood BMI may be central to the development and rising incidence of all diabetes.     

2 型糖尿病与干眼症的相关性研究及其危险因素分析

目的:探讨2型糖尿病和干眼症的关系并分析2型糖尿病发生干眼症的危险因素。方法:纳入2型糖尿病患者220例为观察组和健康人群50例为对照组,采集所有研究对象眼表失衡指数(OSDI)、泪膜破裂时间(TBUT)、泪液分泌试验(SIt),以及观察组性别、年龄、糖尿病病程、血糖、Hb A1c、HOMA-IR、血清CRP,对比分析两组患者干眼症发病率及干眼症症状,采用多因素Logistic回归分析影响2型糖尿病发生干眼症的危险因素。结果:对照组干眼症发病率(9/100,9.00%)明显低于观察组(108/440眼,24.52%)(P0.05)。观察组OSDI评分明显高于对照组(P0.05)。观察组TBUT、SIt明显小于对照组,两组间差异有统计学意义(P0.05)。性别、年龄、糖尿病病程、OSDI、TBUT、SIt、Hb A1c和2型糖尿病患者发生干眼症具有一定的相关性(P0.05)。年龄、糖尿病病程、TBUT、Hb A1c是2型糖尿病患者发生干眼症的危险因素(B0,OR1)。结论:2型糖尿病和干眼症具有一定的相关性,糖尿病患者年龄、糖尿病病程、血糖控制水平是2型糖尿病发生干眼症的独立危险因素。     

Rising incidence of insulin dependent diabetes in children aged under 5 years in the Oxford region: time trend analysis. The Bart's-Oxford Study Group.

OBJECTIVES: To monitor incidence of insulin dependent diabetes in children in Oxford health region since 1985, and to look for any evidence of disproportionate increase in children aged under 5. DESIGN: Primary ascertainment of cases of childhood diabetes was by prospective registration of all patients with insulin dependent diabetes diagnosed before age 15 years between 1985 and 1996 and resident in Oxford region at time of diagnosis. This was supplemented by examination of centralised hospital discharge records and death certificates. Secondary case ascertainment was by postal surveys of general practitioners in 1987 and 1996. SETTING: Area formerly administered by Oxford Regional Health Authority. SUBJECTS: 1037 children presenting with insulin dependent diabetes under age of 15 years. MAIN OUTCOME MEASURES: Incidence of insulin dependent diabetes in children aged 0-4, 5-9, and 10-14 years during 1985-95. RESULTS: Overall incidence of diabetes in children aged 0-15 was 18.6 cases/100000/year and showed an annual increase of 4% from 1985 to 1996. This was mainly due to a rapid increase in children aged 0-4 years, in whom there was an annual increase of 11% (95% confidence interval 6% to 15%, P < 0.0001), while the annual increase in those aged 5-9 was 4% (0 to 7%, P = 0.05) and in those aged 10-14 was 1% (-2% to 4%, P = 0.55). CONCLUSIONS: Incidence of insulin dependent diabetes in children aged under 5 years has risen markedly in the Oxford region over the past decade. The cause of the increase is unknown, but environmental influences encountered before birth or in early postnatal life are likely to be responsible.     

Leading causes of childhood death

The over-all rates of death in childhood decreased five to ten fold during the first half of the century, with the greatest drop occurring in deaths due to infections. The death rate due to accidents has shown a relatively slight decrease; hence, accidents are now the leading cause of childhood death, and in California account for 32 per cent of the deaths in the group 1 to 15 years of age. In California, and among certain insured groups of children, cancer is the leading or second leading cause of death due to disease. There is indication that the incidence of leukemia is increasing in early childhood and in the older age groups.Accidents, the leading cause of childhood death, do not happen; they are caused, and so can be prevented. The medical profession should concern itself much more actively in the field of accident prevention.     

Prospective study of incidence of juvenile diabetes mellitus over 10 years in Dar es Salaam,Tanzania.

OBJECTIVE--To ascertain the annual incidence of diabetes requiring treatment with insulin in children and adolescents aged 0-19 years in Dar es Salaam, Tanzania, during a 10 year period from 1 January 1982 to 31 December 1991. DESIGN--Prospective registration at a major urban hospital of all patients with newly diagnosed diabetes who were resident in Dar es Salaam. SETTING--Muhimbili Medical Centre, Dar es Salaam, Tanzania. PATIENTS--86 patients: 45 male, 41 female. RESULTS--The annual incidence of juvenile diabetes for both sexes was 1.5 per 100,000 population aged 0-19 years (95% confidence interval 1.3 to 1.7). Incidence per 100,000 population per year increased with age: 0.6 (0.0 to 0.13) in the age group 0-4 years, 0.5 (0.3 to 0.7) at 5-9 years, 2.2 (1.8 to 2.6) at 10-14 years, and 3.4 (2.9 to 3.9) at 15-19 years. CONCLUSION--Juvenile diabetes mellitus is fairly rare in sub-Saharan Africa. If environmental factors such as infection and material deprivation were important determinants of insulin dependent diabetes in Africans, as they may be in Europeans, much higher rates would have been expected unless genetic factors possibly exert a protective role. The eightfold greater incidence in African Americans than in Tanzanians may be related to greater genetic admixture in African Americans with people from countries in Europe with a high incidence.     

Increasing Incidence of Pediatric Type 1 Diabetes Mellitus in Southeastern Wisconsin: Relationship with Body Weight at Diagnosis

Introduction

Several studies have confirmed the increasing rate of type 1 diabetes mellitus (T1DM) in children and the link with increasing BMI at diagnosis termed the ‘accelerator hypothesis’. Our objective was to assess whether changing incidence of type 1 diabetes in a group of children and adolescent from the Midwest United States was associated with changes in BMI.

Methods

Data from 1618 (52.1% M/47.9% F) newly-diagnosed children and adolescents (<19 years) with T1DM, admitted to Children''s Hospital of Wisconsin (CHW) between January 1995 and December 2004, was analyzed in relationship to body mass index (BMI) standard deviation score (SDS).

Results

An overall, 10-year cumulative incidence of 27.92 per 100,000 (19.12 to 41.72/100,000) was observed, with an average yearly cumulative incidence of 2.39%. The increase was largest in the younger age groups, 0–4, 5–9, and 10–14 having an average yearly increase of 2.4, 2.3, and 3.0%, respectively, corresponding to a relative 10-year increase of 25.3, 33.8, and 38.0%, respectively. Age at diagnosis was inversely correlated with BMI SDS (p<0.001) and remained significant for both males and females.

Conclusions

Annual incidence of T1DM increased two-fold at CHW over the 10-year study period. The majority of the increase was observed in the youngest age groups, which also appeared to be the heaviest. This research adds to the growing literature supporting the hypothesis that excess weight gain during childhood may be a risk factor for early manifestation of T1DM.     

Coeliac disease in Type 1 diabetes from 1990 to 2009: higher incidence in young children after longer diabetes duration

Diabet. Med. 29, e286-e289 (2012) ABSTRACT: Aims To determine the incidence of coeliac disease in young people with Type?1 diabetes and to examine the effect of age at diabetes onset and disease duration. Methods This was a clinic-based observational cohort study of 4379 people aged ≤?18?years (49% male) between 1990 and 2009 from Sydney, Australia. Screening for coeliac disease was performed at diagnosis and 1-2?yearly using anti-endomysial and/or anti-tissue transglutaminase immunoglobulin?A (IgA) antibodies. Coeliac disease was diagnosed by small bowel biopsy based on Marsh score ≥?III. Results Coeliac disease was confirmed by biopsy in 185; of these, 61 (33%) were endomysial or tissue transglutaminase IgA antibody-positive at diabetes diagnosis. Mean age at diabetes onset was 6.6?±?4.0 vs. 8.4?±?4.1?years in those without coeliac disease (P?相似文献   

Study of Childhood Urinary Tract Infection in General Practice

A study of bacteriuria was conducted among 426 of the 436 children under the age of 13 in a general practice in north-west London. Three girls and one boy were found to have asymptomatic bacteriuria, and a further girl with bacteriuria presented with abdominal pain and fever. The calculated incidence of urinary tract infection was 1·4% per annum. Most of the childhood urinary infections in this practice occurred before the age of 5 years, and the incidence of significant bacteriuria in this age group was 4·9% per annum. Five other children (four girls and one boy) in the practice were known to have had proved urinary tract infection. Of the total of eight children known to have had significant bacteriuria and investigated radiologically, three girls and two boys had radiological abnormalities in the urinary tract.Pyuria and proteinuria did not prove to be useful in the prediction of asymptomatic bacteriuria. Urinary tract infection with renal tract abnormality was found in this practice to be at least five times as common as diabetes in childhood.     

The rising incidence of type 1 diabetes in south-eastern Poland. A study of the 0-29 year-old age group, 1980-1999

INTRODUCTION: Studies carried out over the last few years have provided information about the increase in the incidence of type 1 diabetes in different parts of the world including the European countries bordering Poland. THE AIM OF STUDY: The aim of this study was to determine the long-term trends in the incidence of type 1 diabetes over the 20 years between 1980 and 1999 and to compare the incidence during the decades preceding and following the 1989 economic and political transformation in Poland. MATERIAL AND METHODS: The registration of type 1 diabetes among people aged 0-29 was drawn up according to the DERI recommendations using three data sources. We calculated the age-standardised incidence rates for five-year age groups and determined the long-term trend in the incidence of type 1 diabetes in south-eastern Poland. RESULTS: A significant growth in the incidence of type 1 diabetes was observed among people aged 0-29 in the Rzeszów Province in the period between 1980 and 1999. The mean age-standardised incidence rate was 6.1/100,000, and a statistically significant difference was noted between the 1980s and the 1990s (5.3 [95%CI 4.5-6.0] and 6.8 [95%CI 5.9-7.6]). The male incidence of 6.7 significantly exceeded that for females--5.5/100,000. There was also a higher incidence in the group aged 0-14 in comparison with the group aged 15-29 (6.4 and 5.8/100,000 respectively). The highest incidence was found in boys aged 10-14 (11.5/100,000) and a significantly rising trend was observed in children of 0-4 years old. CONCLUSIONS: The mean incidence of type 1 diabetes among the study population was low. Nevertheless, we demonstrated a significantly increasing trend in the incidence during the 20-year observation period. The incidence in the 1990s, both in general and for males, was significantly higher when compared to the 1980s.     

Register of newly diagnosed diabetic children.

In November 1972 the British Diabetic Association sponsored a register to which notification was invited of all new cases of diabetes occurring in children aged 0-15 years in Great Britain and Ireland. More than 2000 cases were notified in the first two years. Notification suggested that there was a minimum yearly incidence of 7-67 cases per 100 000, though incidences varied from year to year and by geographical area. Several reports of simultaneous onset of diabetes in sibs of different ages provided evidence of clustering. A seasonal variation in incidence was found in children aged 5-15 years with peaks in the autumn and winter. The age distribution was bimodal with a main peak at about 11 years and a secondary peak at about 5 years. The sex ratio showed a male excess from 0-4 years and from 11-15 years and a female excess from 5-10 years. Overall there were slightly more male cases. Altogether 11% of patients had a first-degree relative with diabetes. The register and several investigations based on it will continue.     

A Risk Assessment Model for Type 2 Diabetes in Chinese

Aims

To develop a risk assessment model for persons at risk from type 2 diabetes in Chinese.

Materials and Methods

The model was generated from the cross-sectional data of 16246 persons aged from 20 years old and over. C4.5 algorithm and multivariate logistic regression were used for variable selection. Relative risk value combined with expert decision constructed a comprehensive risk assessment for evaluating the individual risk category. The validity of the model was tested by cross validation and a survey performed six years later with some participants.

Results

Nine variables were selected as risk variables. A mathematical model was established to calculate the average probability of diabetes in each cluster''s group divided by sex and age. A series of criteria combined with relative RR value (2.2) and level of risk variables stratified individuals into four risk groups (non, low, medium and high risk). The overall accuracy reached 90.99% evaluated by cross-validation inside the model population. The incidence of diabetes for each risk group increased from 1.5 (non-risk group) to 28.2(high-risk group) per one thousand persons per year with six years follow-up.

Discussion

The model could determine the individual risk for type 2 diabetes by four risk degrees. This model could be used as a technique tool not only to support screening persons at different risk, but also to evaluate the result of the intervention.     

Five-Year Incidence of Chronic Kidney Disease (Stage 3-5) and Associated Risk Factors in a Spanish Cohort: The MADIABETES Study

Objective

To evaluate the incidence rate of Chronic Kidney Disease (CKD) stage 3-5 (persistent decreased kidney function under 60 mL/min per 1.73 m²) among patients with type 2 diabetes over five years, to identify the risk factors associated with CKD, and develop a risk table to predict five-year CKD stage 3-5 risk stratification for clinical use.

Design

The MADIABETES Study is a prospective cohort study of 3,443 outpatients with type 2 diabetes mellitus, sampled from 56 primary health care centers (131 general practitioners) in Madrid (Spain).

Results

The cumulative incidence of CKD stage 3-5 at five-years was 10.23% (95% CI = 9.12–11.44) and the incidence density was 2.07 (95% CI = 1.83–2.33) cases per 1,000 patient-months or 2.48 (95% CI = 2.19–2.79) cases per 100 patient-years. The highest hazard ratio (HR) for developing CKD stage 3-5 was albuminuria ≥300 mg/g (HR = 4.57; 95% CI= 2.46-8.48). Furthermore, other variables with a high HR were age over 74 years (HR = 3.20; 95% CI = 2.13–4.81), a history of Hypertension (HR = 2.02; 95% CI = 1.42–2.89), Myocardial Infarction (HR= 1.72; 95% IC= 1.25–2.37), Dyslipidemia (HR = 1.68; 95% CI 1.30–2.17), duration of diabetes mellitus ≥ 10 years (HR = 1.46; 95% CI = 1.14-1.88) and Systolic Blood Pressure >149 mmHg (HR = 1.52; 95% CI = 1.02–2.24).

Conclusions

After a five-year follow-up, the cumulative incidence of CKD is concordant with rates described in Spain and other countries. Albuminuria ≥ 300 mg/g and age over 74 years were the risk factors more strongly associated with developing CKD (Stage 3-5). Blood Pressure, lipid and albuminuria control could reduce CKD incidence of CKD in patients with T2DM.     

Investigation on Hyperuricemia in Children with Obesity or Various Pediatric Disorders

The present study aims at investigating the frequency and characteristics of hyperuricemia in both obese and sick children. First, we established our own reference values for serum uric acid (UA), since UA values are highly dependent upon age. In the analysis of 328 samples consisting of six different age groups: <1, 1–3, 4–6, 7–9, 10–12, and 13–15 years, the mean values for UA were found to increase significantly with an increase of age. A significant sex difference was observed only in the age group of 13–15 years. Hyperuricemia was defined as the values over the mean value plus 2 standard deviations for each age group. Next, we examined the frequency of hyperuricemia in 1,687 obese children aged 6–15 years and its relation to metabolic syndrome (MetS). A total of 328 children (19.4%) were found to have hyperuricemia. Among them, 98 children (29.9%) had MetS, whereas 197 (14.5%) out of 1,359 children without hyperuricemia had MetS. Finally, the frequency of hyperuricemia in sick patients was investigated using 13,675 samples from 9,405 patients. Hyperuricemia was seen in 348 (3.7%) patients after excluding redundant samples. The number of patients with hyperuricemia was higher in males than in females. The most common disorder causing hyperuricemia was gastroenteritis, followed by respiratory tract infection and cardiac diseases. This first comprehensive study of childhood hyperuricemia is useful for considering its relationship with hyperuricemia and life-style-related disorders occurring in adulthood.     

Investigation on hyperuricemia in children with obesity or various pediatric disorders

The present study aims at investigating the frequency and characteristics of hyperuricemia in both obese and sick children. First, we established our own reference values for serum uric acid (UA), since UA values are highly dependent upon age. In the analysis of 328 samples consisting of six different age groups: <1, 1-3, 4-6, 7-9, 10-12, and 13-15 years, the mean values for UA were found to increase significantly with an increase of age. A significant sex difference was observed only in the age group of 13-15 years. Hyperuricemia was defined as the values over the mean value plus 2 standard deviations for each age group. Next, we examined the frequency of hyperuricemia in 1,687 obese children aged 6-15 years and its relation to metabolic syndrome (MetS). A total of 328 children (19.4%) were found to have hyperuricemia. Among them, 98 children (29.9%) had MetS, whereas 197 (14.5%) out of 1,359 children without hyperuricemia had MetS. Finally, the frequency of hyperuricemia in sick patients was investigated using 13,675 samples from 9,405 patients. Hyperuricemia was seen in 348 (3.7%) patients after excluding redundant samples. The number of patients with hyperuricemia was higher in males than in females. The most common disorder causing hyperuricemia was gastroenteritis, followed by respiratory tract infection and cardiac diseases. This first comprehensive study of childhood hyperuricemia is useful for considering its relationship with hyperuricemia and life-style-related disorders occurring in adulthood.     

Increasing incidence and survival of paediatric and adolescent thyroid cancer in Cyprus 1998–2017: A population-based study from the Cyprus Pediatric Oncology Registry

BackgroundPaediatric and adolescent thyroid cancer incidence rates are increasing in many countries. We determined incidence rates, temporal trends and survival from thyroid cancer diagnosed in childhood and adolescence in Cyprus during 1998−2017.MethodsPatients aged 0–19 years, diagnosed with thyroid cancer in the Pediatric Oncology Registry of Cyprus were included. Crude incidence rates, age standardized rates, time trends and overall survival were analysed. Annual rates and temporal trends were calculated using Microsoft Excel 2016 and Joinpoint regression analysis.ResultsEighty-one cases (76.5 % female, 23.5 % male) were identified. The crude rates (per 100,000 persons) were for both sexes 2.00 (95 % CI 1.61, 2.49), females 3.15 (95 % CI 2.45, 4.03) and males 0.92 (95 % CI 0.58, 1.44). The annual percentage changes of crude and standardised rates were 7.5 % (p < 0.05) and 7.6 % (p < 0.05). The annual percentage changes of crude rates were for females 5.1 % (p = 0.1), males 8.4 % (p < 0.05) and 15−19-year-olds 7.6 % (p < 0.05). The female to male rate ratio was 3.42 (95 % CI 2.06, 5.74). Papillary thyroid carcinoma represented 86.4 % of all cases. There was only one case after previous cancer therapy. The rate ratio of 2nd (2008−2017) to 1st (1998−2007) periods for metastatic (regional) stages was 3.76 (95 % CI 1.74, 8.31). Survival until 2018 was 100 %.ConclusionThis population-based study demonstrated that thyroid cancer incidence rates in 0–19-year-olds in Cyprus was among the world’s highest. Increasing trends mainly affected males and females aged 15−19 years with papillary thyroid carcinoma, the dominant type. Cases after previous cancer therapy didn’t contribute to increasing rates. The increase of metastatic cases suggests a true increase of thyroid cancer rather than overdiagnosis. Although prognosis is excellent with 100 % survival, the rising incidence rate is unexplained, indicating the need to identify causes.     

The Effect of Long-Term Use of U-500 Insulin Via Continuous Subcutaneous Infusion on Durability of Glycemic Control and Weight in Obese,Insulin-Resistant Patients with Type 2 Diabetes

ObjectiveTo evaluate the long-term efficacy and safety of U-500 insulin administered via continuous subcutaneous insulin infusion (CSII) in patients with insulin-resistant type 2 diabetes and high insulin requirements.MethodsWe retrospectively reviewed the effects of U-500 insulin administered via CSII on durability of gly-cemic control (HbAlc), body weight, total daily insulin dose, and incidence of hypoglycemia in 59 patients with insulin-resistant type 2 diabetes (duration of treatment 1 to 9.5 years; mean treatment duration 49 months). All variables were analyzed by 1-way analysis of variance (ANOVA) from pre-U-500 baseline to time points from 3 to 114 months.ResultsAfter 3 months of U-500 insulin use, hemoglobin A1c dropped significantly from a mean baseline of 8.3% to a mean value of 7.3% (P = .003), and this improvement was sustained for over 66 months of use. There was no significant overall change in body weight or total daily insulin dose over time with the use of U-500 insulin. For those subjects who did gain weight, there was a parallel increase in insulin dose that correlated with weight gain.The overall incidence of severe hypoglycemia was low over the study period, with a mean occurrence of 0.1 episodes per patient per year.ConclusionsU-500 insulin is safe and effective for extended use (up to 9.5 years) in patients with insulin-resistant type 2 diabetes who require high insulin doses, and provides sustained glycemic control without causing excessive weight gain. (Endocr Pract. 2013;19:196-201)     

Prevention of chronic diabetic complications in type 1 diabetes by co-transplantation of umbilical cord mesenchymal stromal cells and autologous bone marrow: a pilot randomized controlled open-label clinical study with 8-year follow-up

Background aimsTo explore the long-term safety and benefit of umbilical cord mesenchymal stromal cell (MSCs) plus autologous bone marrow mononuclear cell (aBM-MNC) stem cell transplantation (SCT) without immunotherapy in established type 1 diabetes (T1D).MethodsIn the primary completion of this trial (ClinicalTrials.gov identifier: NCT01374854), the authors randomized patients (n = 21 per group) to either SCT or standard care (control) and previously reported effects on insulin secretion. The authors report about the incidence of chronic diabetes complications (primary endpoint) after 8 years of follow-up. The authors also report on secondary endpoints, safety, islet function and metabolic control.ResultsData were obtained from 14 of 21 patients in the SCT group and 15 of 21 patients in the control group who completed follow-up. At 8 years, the incidence of peripheral neuropathy was 7.1% (one of 14) in the SCT group versus 46.7% (seven of 15) in the control group (P = 0.017). The incidence of diabetic nephropathy was 7.1% (one of 14) in the SCT group versus 40.0% (six of 15) in the control group (P = 0.039). The incidence of retinopathy was 7.1% (one of 14) in the SCT group versus 33.3% (five of 15) in the control group (P = 0.081). Two patients (two of 14, 14.3%) in the SCT group and 11 patients (11 of 15, 73.3%) in the control group developed at least one complication (P = 0.001). One and six patients in the SCT group and control group, respectively, had at least two complications (P = 0.039). No malignancies were reported in the treated group.ConclusionsCo-transplantation of umbilical cord MSCs and aBM-MNCs in patients with established T1D was associated with reduced incidence of chronic diabetes complications.