Increased risk of cardiovascular disease in young women following gestational diabetes mellitus

OBJECTIVE—To determine whether women with gestational diabetes mellitus (GDM) have an increased risk of cardiovascular disease (CVD) following pregnancy.RESEARCH DESIGN AND METHODS—All women aged 20–49 years with live births between April 1994 and March 1997 in Ontario, Canada, were identified. Women with GDM were matched with 10 women without GDM and were followed for CVD.RESULTS—The matched cohorts included 8,191 women with GDM and 81,262 women without GDM. Mean age at entry was 31 years, and median follow-up was 11.5 years. The hazard ratio for CVD events was 1.71 (95% CI 1.08–2.69). After adjustment for subsequent type 2 diabetes, the hazard ratio was attenuated (1.13 [95% CI 0.67–1.89]).CONCLUSIONS—Young women with GDM had a substantially increased risk for CVD compared with women without GDM. Much of this increased risk was attributable to subsequent development of type 2 diabetes.Gestational diabetes mellitus (GDM) is a common condition affecting 2–4% of pregnant women (1) and is associated with adverse outcomes for both the fetus and the mother. Previous GDM is a major risk factor for type 2 diabetes, which occurs in 20–60% of affected women within 5 years of the pregnancy (2). Women with a history of GDM are also at increased risk of other cardiovascular risk factors, such as obesity, hypertension, dyslipidemia, and the metabolic syndrome (3–5), as well as subclinical atherosclerosis (6). Taken together, these findings suggest that GDM identifies a population of young women at increased risk for cardiovascular disease (CVD). We used population-based administrative data to determine whether women with GDM have a heightened risk for CVD compared with women without GDM and whether any increase in risk is independent of subsequent type 2 diabetes.     

Quantifying the risk of infectious diseases for people with diabetes

OBJECTIVE: In vitro evidence shows that immune function is compromised in people with diabetes. Although certain rare infections are more common and infection-related mortality is higher, the risk of acquiring an infectious disease for diabetic patients has never been quantified. RESEARCH DESIGN AND METHODS: A retrospective cohort study using administrative data compared all people with diabetes in Ontario, Canada, on 1 April 1999 to matched nondiabetic people (n = 513,749 in each group). The risk ratios of having an infectious disease and of death attributable to infectious disease between those with and without diabetes were calculated. Secondary analysis individually examined common infectious diseases. The study was repeated using a second pair of cohorts defined in 1996 to confirm stability of the estimates. RESULTS: Nearly half of all people with diabetes had at least one hospitalization or physician claim for an infectious disease in each cohort year. The risk ratio for diabetic versus nondiabetic people was 1.21 (99% CI 1.20-1.22) in both cohort years. The risk ratio for infectious disease-related hospitalization was up to 2.17 (99% CI 2.10-2.23). The risk ratio for death attributable to infection was up to 1.92 (1.79-2.05). Many individual infections were more common in people with diabetes, especially serious bacterial infections. CONCLUSIONS: Diabetes confers an increased risk of developing and dying from an infectious disease, corroborating both in vitro evidence and commonly held clinical belief. In addition to microvascular and macrovascular sequelae, clinicians should consider infection a complication of diabetes.     

Detecting location-specific neuronal firing rate increases in the hippocampus of freely-moving monkeys

The spatial properties of the firing of hippocampal neurons have mainly been studied in (a) freely moving rodents, (b) non-human primates seated in a moveable primate chair with head fixed, and (c) epileptic patients subjected to virtual navigation. Although these studies have all revealed the ability of hippocampal neurons to generate spatially selective discharges, the detected firing patterns have been found to be considerably different, even conflicting, in many respects. The present cellular electrophysiological study employed squirrel monkeys (Saimiri sciureus), which moved freely on the walls and floor of a large test chamber. This permitted the examination of the spatial firing of hippocampal neurons in nearly ideal conditions, similar to those used in rodents, yet in a species that belongs to the primate Suborder Anthropoidea. The major findings were that: (1) a group of slow-firing complex-spike cells increased their basal, awake firing rate more than 20-fold, often above 30 spikes/s, when the monkey was in a particular location in the chamber, (2) these location-specific discharges occurred consistently, forming 4-25 s action potential volleys, and (3) fast-firing cells displayed no such electrical activity. Thus, during free movement in three dimensions, primate hippocampal complex-spike cells do generate high-frequency, location-specific action potential volleys. Since these cells are components of the medial temporal lobe memory system, their uncovered firing pattern may well be involved in the formation of declarative memories on places.     

Spatial memory performance of freely-moving squirrel monkeys

Few experiments have addressed the problem of cognitive map formation in non-human primates. Therefore, a paradigm was developed to assess spatial memory formation in squirrel monkeys (Saimiri sciureus) moving freely in three dimensions. While moving on the walls and floor of a large test chamber, the animals learned to collect pieces of cereal from baited food-ports interspersed among non-baited ports. The cereal-pellets were not visible to the monkeys, so the animals needed to develop spatial memory to visit only the baited ports for food and avoid the non-baited ones. A session consisted of ten consecutive trials, and 3 successive sessions were conducted on each day for a 5-day period. For each trial, correct choices (CC; number of visited baited-ports) and incorrect choices (IC; number of visited non-baited ports) were registered, and spatial memory performance index (SMPI; ranging from 0.00 to 1.00) was calculated as follows: SMPI=(CC−IC)/CC. For each session, mean SMPI, session duration, total reaches into the non-baited ports, and total reaches into the baited ports were documented. In an 8-port task, where 4 food-ports were baited and 4 were non-baited, the mean SMPI was higher than 0 in the first session (day 1), indicating the development of short-term spatial memory. By the fifth session (day 2), this index was significantly higher than in the first session, indicating the build-up of long-term spatial memory. These changes were related to a significant decrease in the total reaches into the non-baited ports. At the same time, the duration of the sessions and the total reaches into the baited ports did not change significantly. This paradigm can be used for (1) studying cognitive map formation in primates, (2) examining the underlying cellular and molecular mechanisms in integrative neurobiological experiments, and (3) screening cognition-enhancer drugs in a monkey model.     

尿酸对人骨髓间充质干细胞成骨分化中Cbfα1/Runx2表达的影响

目的 观察不同浓度尿酸对人骨髓间充质干细胞(hBMSCs)成骨分化过程中核心结合因子α1(Cbfα1/Runx2)表达变化的影响.方法 以体外培养的健康成年hBMSCs为研究对象,分为5个组,分别为对照组(完全培养基组)和加入不同浓度尿酸(0 mmol/l、0.2 mmol/l、0.4 mmol/l、0.8mmol/l)的成骨诱导组,通过倒置显微镜观察细胞形态,碱性磷酸酶染色和茜素红染色鉴定细胞.在干预诱导第7天和第14天行RT-PCR检测Cbfα1/Runx2的表达.结果 碱性磷酸酶染色和茜素红染色结果均阳性,表示诱导后细胞为成骨细胞.RT-PCR结果表明,对照组各时间点均无Cbfα1/Runx2表达,尿酸培养组随尿酸浓度增加和时间的延长,Cbfα1/Runx2表达逐渐增强,呈现时间依赖性和浓度依赖性.结论 尿酸可能通过促进Cbfα1/Runx2的表达,从而促进hBMSCs向成骨细胞分化.     

The burden of asthma among South Asian and Chinese populations residing in Ontario

BACKGROUND:The South Asian and Chinese populations represent a significant portion of the population of Ontario; however, little is known about the burden of respiratory diseases in these populations.OBJECTIVE:To investigate the prevalence of asthma and the associated health care burden among South Asian and Chinese populations living in Ontario.METHODS:Using administrative health data for Ontario, the authors identified individuals of South Asian and Chinese descent using a validated surname algorithm and compared the prevalence of asthma in these groups with the general population using an established asthma case definition for the period 2002 to 2010. Also compared were the rates of asthma-specific emergency department visits and hospitalizations among the ethnic groups.RESULTS:In 2010, the prevalence of asthma in South Asians residing in Ontario was similar to that of the general population (12.1% versus 12.4%), and was increasing at a faster rate than in the general population (0.51%/year versus 0.34%/year). Compared with the general population, the South Asian population had fewer emergency department visits for asthma, whereas the asthma-related hospitalization rate was greatest among the South Asian population (0.45 per 100 person-years). The Chinese population had the lowest asthma prevalence and associated health care use.CONCLUSION:The burden of asthma among South Asians in Ontario is increasing and warrants further investigation to determine the reasons for this rise.     

Cardiovascular Complications and Mortality After Diabetes Diagnosis for South Asian and Chinese Patients: A population-based cohort study

OBJECTIVE

Many non-European ethnic groups have an increased risk for diabetes; however, the published literature demonstrates considerable uncertainty about the rates of diabetes complications among minority populations. The objective of this study was to determine the risks of cardiovascular complications and of mortality after diabetes diagnosis for South Asian and Chinese patients, compared with European patients.

RESEARCH DESIGN AND METHODS

A population-based cohort study identified all 491,243 adults with newly diagnosed diabetes in Ontario, Canada, between April 2002 and March 2009. Subjects were followed until March 2011 for the first occurrence of any cardiovascular complication of diabetes (coronary artery disease, stroke, or lower-extremity amputation) and for all-cause mortality. Median follow-up was 4.7 years.

RESULTS

The crude incidence of cardiovascular complications after diabetes diagnosis was 17.9 per 1,000 patient-years among European patients, 12.0 among South Asian patients, and 7.7 among Chinese patients. After adjusting for baseline characteristics, the cause-specific hazard ratios (HRs) for cardiovascular complications relative to European patients were 0.95 (95% CI 0.90–1.00; P = 0.056) and 0.50 (0.46–0.53; P < 0.001) for South Asian and Chinese patients, respectively. Mortality was lower for both minority groups (adjusted HR for South Asian patients 0.56 [95% CI 0.52–0.60]; P < 0.001; for Chinese patients 0.58 [0.55–0.62]; P < 0.001).

CONCLUSIONS

Chinese patients were at substantially lower risk than European patients for cardiovascular complications after diabetes diagnosis, whereas South Asian patients were at comparable risk. Mortality after diabetes diagnosis was markedly lower for both minority populations.Many non-European ethnic groups have an increased prevalence (1,2) and incidence (3,4) of diabetes mellitus; however, the published literature demonstrates considerable uncertainty about the rates of diabetes complications among minority populations. Studies in the U.S. have shown African American and Hispanic populations to have rates of cardiovascular complications similar to or lower than those of Europeans (5,6). Mortality rates are decreased for Hispanic populations with diabetes and increased for African Americans (7,8). Data are limited in other ethnic groups, however, and also from other countries where universal health care systems may mitigate some barriers to care for minority patients.The two largest minority ethnic groups in Canada are South Asians (ancestry from the Indian subcontinent) and Chinese (ancestry from China, Hong Kong, or Taiwan) (9). Our previous research has shown that people with diabetes from these two groups have equitable utilization and quality of care (10,11). The objective of this study was to examine whether outcomes of care were also equitable. We sought to determine the risk of cardiovascular complications and of mortality after diagnosis with diabetes, comparing South Asian and Chinese patients with those of European ancestry.     

Surgical repair of double-chambered right ventricle in adulthood

The aim of this study was to investigate a rare subset of adult patients with double-chambered right ventricle, pertaining to clinical presentation, rhythm disturbances, surgical approach, and results of surgical repair. A retrospective review of our records revealed that 14 adults had undergone surgical repair of double-chambered right ventricle from 1990 to 2010. Their median age was 25.5 years, and their median weight was 50 kg. Patients presented with various symptoms, the most common being dyspnea on exertion. The mean systolic pressure gradient across the obstruction was 69.8 ± 23.1mm Hg. The most common associated anomaly was ventricular septal defect. Significant rhythm disturbances were present in 4 patients. Transatrial repair was undertaken in 5 patients, a combined transatrial and transpulmonary approach was used in 4, and a right ventriculotomy in 5. There was no mortality at a median follow-up of 5.1 years. A mild right ventricular outflow tract gradient was noted in 2 patients. Medical management was required for rhythm disturbances in 2 patients. Double-chambered right ventricle can present in adulthood, often with vague symptoms. The midterm results of surgical correction are satisfactory. Long-term follow-up is necessary to detect late arrhythmias.     

Deriving ethnic-specific BMI cutoff points for assessing diabetes risk

OBJECTIVE

The definition of obesity (BMI ≥30 kg/m²), a key risk factor of diabetes, is widely used in white populations; however, its appropriateness in nonwhite populations has been questioned. We compared the incidence rates of diabetes across white, South Asian, Chinese, and black populations and identified equivalent ethnic-specific BMI cutoff values for assessing diabetes risk.

RESEARCH DESIGN AND METHODS

We conducted a multiethnic cohort study of 59,824 nondiabetic adults aged ≥30 years living in Ontario, Canada. Subjects were identified from Statistics Canada’s population health surveys and followed for up to 12.8 years for diabetes incidence using record linkages to multiple health administrative databases.

RESULTS

The median duration of follow-up was 6 years. After adjusting for age, sex, sociodemographic characteristics, and BMI, the risk of diabetes was significantly higher among South Asian (hazard ratio 3.40, P < 0.001), black (1.99, P < 0.001), and Chinese (1.87, P = 0.002) subjects than among white subjects. The median age at diagnosis was lowest among South Asian (aged 49 years) subjects, followed by Chinese (aged 55 years), black (aged 57 years), and white (aged 58 years) subjects. For the equivalent incidence rate of diabetes at a BMI of 30 kg/m² in white subjects, the BMI cutoff value was 24 kg/m² in South Asian, 25 kg/m² in Chinese, and 26 kg/m² in black subjects.

CONCLUSIONS

South Asian, Chinese, and black subjects developed diabetes at a higher rate, at an earlier age, and at lower ranges of BMI than their white counterparts. Our findings highlight the need for designing ethnically tailored prevention strategies and for lowering current targets for ideal body weight for nonwhite populations.Type 2 diabetes is a growing epidemic. There currently are an estimated 285 million people with known type 2 diabetes (henceforth “diabetes”) worldwide; this number is projected to rise to ~438 million by 2030, with a disproportionate burden expected in developing countries, particularly India and China, and among ethnic minorities living in wealthier nations (1). Earlier cross-sectional studies (2–4) have reported ethnic differences in the prevalence of diabetes; however, to date there have been no longitudinal studies comparing the incidence rate and age at diagnosis of diabetes across the world’s four major ethnic groups (white, South Asian, Chinese, and black populations) and among individuals from these four groups living in the same social macroenvironment.Although the definition of obesity (BMI ≥30 kg/m²), a key risk factor of diabetes, has been validated in white populations (5), its appropriateness in Asian populations has been questioned (6). Recognizing this, a World Health Organization (WHO) expert panel was convened in 2002 to discuss the potential for developing Asian-specific BMI cutoff points for obesity (7). The consultation concluded that with the data available at the time, there was no clear BMI cutoff point that would be universally applicable to Asians and that the prespecified BMI ranges would be retained (i.e., underweight <18.5 kg/m², normal 18.5 to <25 kg/m², overweight 25 to <30 kg/m², and obese ≥30 kg/m²) for assessing the risk of obesity-related chronic diseases. Nevertheless, the WHO expert panel recommended potential BMI categories for public health action in people of Asian descent (i.e., underweight <18.5 kg/m², increasing but acceptable risk 18.5 to <23 kg/m², increased risk 23 to <27.5 kg/m², and high risk ≥27.5 kg/m²) (7). The WHO panel also emphasized the need for longitudinal studies using disease outcomes data to better understand the relationship between BMI and obesity-related diseases and to derive and validate ethnic-specific BMI cutoff points. Because of these recommendations, several studies have attempted to redefine obesity for Asians. A systematic review (8) of these studies found that, although most studies were in favor of lowering the BMI cutoff point for obesity in Asians, the majority of these studies used cross-sectional data and some did not report health outcomes.The two main objectives of this multiethnic cohort study were 1) to compare the incidence and age at diagnosis of diabetes across white, South Asian, Chinese, and black subjects living in Ontario, Canada, one of the world’s most ethnically diverse regions; and 2) to derive ethnically appropriate population-based BMI cutoff values for obesity in assessing diabetes risk using clinically ascertained diabetes. A cutoff point of a BMI of 30 kg/m² was chosen because it represents the current standard for obesity, a key risk factor of diabetes.