Article

Developmental origins of type 2 diabetes: a perspective from China

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Abstract

There has been a marked increase in the prevalence of diabetes in Asia, including China, over the last few decades. While the increased prevalence of diabetes has often been attributed to the nutritional transition associated with recent economic development, emerging data suggest that early-life exposures also play a major role in shaping developmental trajectories, and contributes to alter an individual's susceptibility to diabetes and other non-communicable diseases (NCDs). Early-life exposures such as in utero exposure to undernutrition has been consistently linked with later risk of diabetes and obesity. Furthermore, in utero exposure to maternal hyperglycemia, maternal obesity and excess gestational weight gain are all linked with increased childhood obesity and later risk of diabetes. Emerging data have also highlighted the potential link between early-feeding practices, the role of one-carbon metabolism in metabolic programming and endocrine disrupting chemicals (EDCs) with later risk of diabetes. These different developmental exposures may all be highly relevant to the current epidemic of diabetes in China. For example, the prevalence of gestational diabetes has increased markedly over the last two decades, and may contribute to the diabetes epidemic by driving macrosomia, childhood obesity and later risk of diabetes. In order to address the current burden of diabetes, a lifecourse perspective, incorporating multisectoral efforts from public health policy down to the individuals, will be needed. Several major initiatives have been launched in China as part of its national plans for NCD prevention and treatment, and the experience from these efforts would be invaluable.European Journal of Clinical Nutrition advance online publication, 5 April 2017; doi:10.1038/ejcn.2017.48.

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... Another emerging issue is the importance of developmental origins of diabetes and early life exposures [20]. Different studies have highlighted the increased risk of diabetes among offspring who were exposed to undernutrition in utero but exposed to overnutrition later in life. ...
... There is also growing recognition of the increased risk of obesity and glucose intolerance among offspring of mothers with pre-existing diabetes, gestational diabetes mellitus (GDM) or maternal obesity, highlighting the intergenerational effects of maternal hyperglycaemia [20,22]. For example, maternal GDM (diagnosed according to International Association Diabetes prevalence (%) Fig. 1 Prevalence of diabetes in China over recent decades. ...
... Given the adverse long-term prognosis of individuals with young-onset diabetes [26][27][28], this trend of suboptimal control among those with early-onset disease is particularly alarming. Furthermore, the increasing prevalence of young-onset diabetes results in an increasing proportion of men and women at reproductive age being affected by hyperglycaemia, with potential intergenerational effects [20,22]. ...
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The People’s Republic of China (herein referred to as China) has witnessed one of the most dramatic rises in diabetes prevalence anywhere in the world. The latest epidemiological study suggests that approximately 11% of the population has diabetes, with a significant proportion remaining undiagnosed. Risk factors for diabetes in the Chinese population are similar to those in other populations, though gestational diabetes and young-onset diabetes is becoming increasingly common. Data on the prevalence of diabetic complications remain limited, though cardio–renal complications account for significant morbidity and mortality. Other diabetes-related comorbidities are becoming increasingly common, with cancer emerging as a major cause of mortality among individuals with diabetes. There are many challenges and obstacles that impede effective diabetes prevention and the delivery of care, though much progress has occurred over recent years. Lessons learnt from how China has responded to the challenges posed by the diabetes epidemic will be invaluable for other countries facing the many threats of diabetes and its complications.
... Clearly, China has gone through rapid changes since 1980 when the low diabetes prevalence was reported in Shanghai (8). This dramatic, epidemic increase in diabetes may have a number of interrelated and interacting causes, many associated with industrialization and globalization with the consequential changes in lifestyle (1,12,13). But there is one other potential factor, the subject of increasing interest in epidemiology and public health, the impact of deleterious effect of the intrauterine environment and the resulting epigenetic changes that may also convey increased risk of type 2 diabetes and other chronic diseases in adult life (1,(13)(14)(15). ...
... This dramatic, epidemic increase in diabetes may have a number of interrelated and interacting causes, many associated with industrialization and globalization with the consequential changes in lifestyle (1,12,13). But there is one other potential factor, the subject of increasing interest in epidemiology and public health, the impact of deleterious effect of the intrauterine environment and the resulting epigenetic changes that may also convey increased risk of type 2 diabetes and other chronic diseases in adult life (1,(13)(14)(15). These epigenetic changes can be transmitted to future generations (16) and therefore become intergenerational. ...
... Because national estimates of the diabetes burden have important implications for future public health planning, it is essential that they provide reliable data to understand and address the drivers of the epidemic (3). In particular, those relating to developmental origins of type 2 diabetes and its comorbidities should be included (13,14). This would provide a more comprehensive and far-sighted approach for prevention strategies to address this rising public health "tsunami." ...
... Previous reviews have discussed in detail the putative risk factors that might have contributed to the T2DM epidemic in China 31,32 . As suggested, and as discussed here, a potential candidate and contributor to the major increase in T2DM has been the impact of early development risk factor exposures in utero during the 1959-1961 Chinese Famine 31 . ...
... The regional prevalence of T2DM ranged from 8.3% in the northeast to 12.7% in the north. Personal characteristics (for example, overweight or obesity, unhealthy lifestyle and health literacy) did not fully account for geographic variation, but it has been suggested that differences in ethnicity, lifestyle and pollution might contribute to the disparity 31 . ...
Article
The gene–environment interactions resulting from famine and the subsequent increased intergenerational risk of type 2 diabetes mellitus (T2DM) have contributed to the current epidemic of T2DM in China, which poses major social, health and economic challenges. The epidemic of T2DM could threaten national development in China through premature morbidity and mortality from T2DM and associated non-communicable diseases. The Chinese Famine (1959–1961), as a contributor to the nation’s current national T2DM epidemic, provides an important and urgent public health warning. The effects of the famine give a strong message that research and actions that address the prevention of T2DM cannot be confined to lifestyle measures, as used in the landmark Da Qing study and the lifestyle prevention programmes and pharmaceutical interventions used in Western nations. To stem the T2DM epidemic, a new paradigm for prevention of T2DM must be developed. This paradigm should include a very strong emphasis on pregnancy planning and maternal and child health during and after the pregnancy. Without action, intergenerational cycles initiated by epigenetic modifications resulting from adverse environmental stimuli during the critical window of early development in utero might continue to fuel the T2DM epidemic in future generations.
... Previous reviews have discussed in detail the putative risk factors that might have contributed to the T2DM epidemic in China 31,32 . As suggested, and as discussed here, a potential candidate and contributor to the major increase in T2DM has been the impact of early development risk factor exposures in utero during the 1959-1961 Chinese Famine 31 . ...
... The regional prevalence of T2DM ranged from 8.3% in the northeast to 12.7% in the north. Personal characteristics (for example, overweight or obesity, unhealthy lifestyle and health literacy) did not fully account for geographic variation, but it has been suggested that differences in ethnicity, lifestyle and pollution might contribute to the disparity 31 . ...
Article
In the version of this article published online and in print, there was a mistake in the legend of Fig. 2 regarding the descriptions of the red and blue colours in the Figure. The text should have read ‘The blue and red colours represent regions (provinces) with wheat and rice as the staple food, respectively.’ This has now been corrected in the HTML and PDF version of the article.
... High pre-pregnancy BMI or normal upper range of FPG was associated with insulin sensitivity defect, condition which could be involved in the onset of GDM [5,19]. In China, it is traditional for women to increase their calorie consumption and sedentary habit from the onset of pregnancy though this is clearly responsible for increasing diabetogenic burden in high risk women [20]. It should be emphasized that our study was conducted at a time when early identification and targeted interventions are available for those women . ...
Article
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Background: This study sought to develop and validate a nomogram for prediction of gestational diabetes mellitus (GDM) in an urban, Chinese, antenatal population. Methods: Age, pre-pregnancy body mass index (BMI), fasting plasma glucose (FPG) in the first trimester and diabetes in first degree relatives were incorporated as validated risk factors. A prediction model (nomogram) for GDM was developed using multiple logistic regression analysis, from a retrospective study conducted on 3956 women who underwent their first antenatal visit during 2015 in Shanghai. Performance of the nomogram was assessed through discrimination and calibration. We refined the predicting model with t-distributed stochastic neighbor embedding (t-SNE) to distinguish GDM from non-GDM. The results were validated using bootstrap resampling and a prospective cohort of 6572 women during 2016 at the same institution. Results: Advanced age, pre-pregnancy BMI, high first-trimester, fasting, plasma glucose, and, a family history of diabetes were positively correlated with the development of GDM. This model had an area under the receiver operating characteristic (ROC) curve of 0.69 [95% CI:0.67-0.72, p < 0.0001]. The calibration curve for probability of GDM showed good consistency between nomogram prediction and actual observation. In the validation cohort, the ROC curve was 0.70 [95% CI: 0.68-0.72, p < 0.0001] and the calibration plot was well calibrated. In exploratory and validation cohorts, the distinct regions of GDM and non-GDM were distinctly separated in the t-SNE, generating transitional boundaries in the image by color difference. Decision curve analysis showed that the model had a positive net benefit at threshold between 0.05 and 0.78. Conclusions: This study demonstrates the ability of our model to predict the development of GDM in women, during early stage of pregnancy.
... GDM, an abnormal glucose tolerance first recognized in pregnancy, has been found to be 2-3 fold higher in AMA group compared with those aged 20-30 years in China [5,6]. Furthermore, there is an increasing recognition of the increased risk of obesity, glucose intolerance, and cardiovascular disorders among maternal and offspring of GDM with advanced maternal age [7,8]. ...
Article
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Background Gestational diabetes mellitus (GDM) is defined as impaired glucose tolerance in pregnancy and without a history of diabetes mellitus. While there are limited metabolomic studies involving advanced maternal age in China, we aim to investigate the metabolomic profiling of plasma and urine in pregnancies complicated with GDM aged at 35–40 years at early and late gestation. Methods Twenty normal and 20 GDM pregnant participants (≥ 35 years old) were enlisted from the Complex Lipids in Mothers and Babies (CLIMB) study. Maternal plasma and urine collected at the first and third trimester were detected using gas chromatography-mass spectrometry (GC-MS). Results One hundred sixty-five metabolites and 192 metabolites were found in plasma and urine respectively. Urine metabolomic profiles were incapable to distinguish GDM from controls, in comparison, there were 14 and 39 significantly different plasma metabolites between the two groups in first and third trimester respectively. Especially, by integrating seven metabolites including cysteine, malonic acid, alanine, 11,14-eicosadienoic acid, stearic acid, arachidic acid, and 2-methyloctadecanoic acid using multivariant receiver operating characteristic models, we were capable of discriminating GDM from normal pregnancies with an area under curve of 0.928 at first trimester. Conclusion This study explores metabolomic profiles between GDM and normal pregnancies at the age of 35–40 years longitudinally. Several compounds have the potential to be biomarkers to predict GDM with advanced maternal age. Moreover, the discordant metabolome profiles between the two groups could be useful to understand the etiology of GDM with advanced maternal age.
... However, these women are not classified as having type 2 diabetes, as there is not enough research on whether their blood glucose levels normalize or not after the pregnancy. Many older guidelines and studies have classified both DIP and GDM groups as GDM, although DIP may in some cases, imply that the foetus is likely to be exposed to hyperglycaemia for a longer period compared to GDM and consequently, untreated hyperglycaemia for a longer period until screening and treatment [9]. This is because a proportion of women with DIP may consist of women who may have had undiagnosed diabetes until GDM screening during the second trimester pregnancy [10]. ...
Article
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Introduction Little is known about the influence of hyperglycemia first detected in pregnancy (HFDP) on weight outcomes in exposed offspring in Africa. We investigated the influence of maternal blood glucose concentrations during pregnancy on offspring weight outcomes at birth and preschool age, in offspring exposed to HFDP, in South Africa. Research design and methods Women diagnosed with HFDP had data routinely collected during the pregnancy and at delivery, at a referral hospital, and the offspring followed up at preschool age. Maternal fasting, oral glucose tolerance test 1 and 2-hour blood glucose were measured at diagnosis of HFDP and 2-hour postprandial blood glucose during the third trimester. Offspring were classified as either those exposed to diabetes first recognized in pregnancy (DIP) or gestational diabetes (GDM). At birth, neonates were classified into macrosomia, low birth weight (LBW), large for gestational age (LGA), appropriate (AGA) and small for gestational age (SGA)groups. At preschool age, offspring had height and weight measured and Z-scores for weight, height and BMI calculated. Results Four hundred and forty-three neonates were included in the study at birth, with 165 exposed to DIP and 278 exposed to GDM. At birth, the prevalence of LGA, macrosomia and LBW were 29.6%, 12.2% and 7.5%, respectively, with a higher prevalence of LGA and macrosomia in neonates exposed to DIP. At pre-school age, the combined prevalence of overweight and obesity was 26.5%. Maternal third trimester 2-hour postprandial blood glucose was significantly associated with z-scores for weight at birth and preschool age, and both SGA and LGA at birth. Conclusion In offspring exposed to HFDP, there is a high prevalence of LGA and macrosomia at birth, and overweight and obesity at preschool age, with higher prevalence in those exposed to DIP, compared to GDM. Maternal blood glucose control during the pregnancy influences offspring weight at birth and preschool age.
... They show the importance of linking early-life environment shock to increased risk of diabetes for their prevention and management, and illustrate the possibility of using the famine as a model to examine the causal effect of prenatal under nutrition on human aging. Their findings have been interpreted as evidence that the prenatal famine exposure drives the T2DM epidemic among Chinese population [5][6][7][8][9][10]. However, such interpretations can be misleading because most Chinese famine studies have major methodologic problems, including poor famine exposure definitions and inappropriate unexposed control selections [2,3,11]. ...
Article
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Famines in human history have been widely used as natural experiments to study how early-life environments may influence adult health outcomes, including overweight/obesity, diabetes and schizophrenia.
... GDM, an abnormal glucose tolerance rst recognized in pregnancy has been found to be 2-3 fold higher in AMA group compared with pregnant women aged 20-30 years in China (6,7). In addition, there is a growing recognition of the increased risk of obesity, glucose intolerance, and cardiovascular disorders among maternal and offspring of GDM with AMA (8,9). ...
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Background: Gestational diabetes mellitus (GDM) is characterized by impaired glucose tolerance in pregnancy and without a history of diabetes mellitus. It can lead to adverse maternal and neonatal outcomes. The incidence of GDM is closely related to maternal age, but there are only a few pregnancy-related metabolomic studies involving advanced maternal age (AMA) in China. Methods: 20 GDM and 20 normal pregnant participants(≥35 years old) were recruited from the Complex Lipids in Mothers and Babies (CLIMB) study. Maternal plasma and urine metabolomes collected at the first and third trimester were analyzed using gas chromatography-mass spectrometry (GC-MS). Results: Of the metabolites identified using GC–MS, 165 metabolites and 192 metabolites were found in plasma and urine respectively. However, urine metabolomic profiles were unable to distinguish GDM from controls, while there were 14 and 39 significantly different metabolites in plasma of the two groups in first and third trimester. Especially, by combining seven metabolites including cysteine, malonic acid, stearic acid, alanine, 11,14-eicosadienoic acid, 2-methyloctadecanoic acid, and arachidic acid using multivariant receiver operating characteristic(ROC) models, we were capable of discriminating GDM from healthy pregnancies with an area under curve (AUC) of 0.928 at early gestation. Conclusion: This study explores metabolomic profiles between GDM and normal pregnancies longitudinally. Several metabolites have the potential to be biomarkers to predict GDM with AMA. Besides, the discordant metabolome profiles between the two groups could be helpful to understand the etiology of elderly GDM.
... 1,2 Furthermore, a large body of evidence supports the importance of maternal nutrition on long-term noncommunicable disease risk for mothers as well as for future generations. 1,[3][4][5] The nutritional status of women in Hong Kong has not been studied in detail, with only a few dietary and nutritional surveys conducted in the past. These studies highlighted inadequate intake of various nutrients, including iodine, 6,7 vitamin D, 8 fiber, calcium, and iron 9 among local women of childbearing age. ...
Article
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Objective: To evaluate the reliability and utility of the FIGO Nutrition Checklist to identify dietary and nutritional inadequacy in early pregnancy by comparing it against nutritional indicators and dietary quality indices (Dietary Approaches to Stop Hypertension [DASH] score, Mediterranean Diet Score [MDS], and Dietary Quality Index-International [DQI-I]), derived by a locally validated food frequency questionnaire (FFQ). Methods: A prospective cohort study of healthy Chinese pregnant women randomly recruited between September 2017 and April 2018 at their first antenatal appointment. Women completed the FIGO Nutrition Checklist (translated into Chinese) and the FFQ. Spearman correlation was performed to examine association between the Checklist and dietary quality indices or food and nutrient intakes, calculated based on dietary data from the FFQ. Results: Of 160 participants, 156 (97.5%) completed both the FIGO Nutrition Checklist and FFQ and were included. There were 148 (95%) women who reported at least one suboptimal dietary behavior using the Checklist. Checklist score was significantly associated with dietary quality indices (DASH ρ=0.344, P<0.001; DQI-I ρ=0.304, P<0.001; MDS ρ=0.164, P=0.041). The Checklist question on fruit/vegetables was significantly associated with fiber, vitamin C, and fruit and vegetable intake as calculated from the FFQ (0.325 ≤ ρ ≤0.441, P<0.001). The question on dairy intake was significantly associated with intake of calcium, milk and dairy products captured via FFQ (0.576 ≤ ρ ≤0.655, P<0.001). Conclusion: This study supports the use of the FIGO Nutrition Checklist to identify women with suboptimal dietary quality in early pregnancy.
... 1,2 In less than 20 years, the number of diabetes in China has increased rapidly from a low prevalence country (< 3% ) to a moderate prevalence country (3%-10% ), and the total cost for this disease is about 2.086 billion Chinese yuan. [3][4][5] There are two types of diabetes, type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM), and the T2DM accounts for more than 90% of all diabetic patients. T2DM is a chronic metabolic disorder caused by abnormal insulin secretion or defect in insulin action, and is a heterogeneous and progressive disease comprehensively caused by several genetic and environmental factors, as well as personal habits. ...
Article
Diabetes mellitus is a chronic endocrine/metabolism disease characterized by hyperglycemia arising from defects in insulin action, insulin secretion, or both. Diabetes mellitus is often complicated by visceral lesions, which can lead to serious complications and death. A variety of new agents are in development for the treatment of the disease. Astragalus polysaccharides are monomer components extracted from the Traditional Chinese Medicine, Huangqi (Radix Astragali Mongolici), which have been studied widely for treating diabetes mellitus with promising effects in recent years. This paper reviews recent advances in experimental studies on the effects of Astragalus polysaccharides in treating diabetes mellitus. The effects of Astragalus polysaccharides on the etiology and complication of diabetes mellitus including insulin resistance and secretion, diabetic neuropathy, diabetic retinopathy, diabetic cardiomyopathy, diabetic foot, and infection complicated by diabetes mellitus are discussed.
... According to the latest statistics, there were about 110 million adults suffering from diabetes in China, and it had rapidly become one of the countries with the medium prevalence (3%-10%) from the previous one with low prevalence (<3%) in less than 20 years [3,4]. At present, the total cost of medical treatment due to diabetes and its complications in China was 20.86 billion yuan per year, accounting for 4.38% of the total national medical expenses, resulting in tremendous personal, family, and socioeconomic burdens [5,6]. ...
Article
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Objective To investigate the effects of Tai chi in type 2 diabetes mellitus (type-2 DM) patients using systematic review and meta-analysis. Methods Seven electronic resource databases were searched, and randomized controlled trials on the role of Tai chi in type-2 DM patients were retrieved. The meta-analysis was performed with RevMan 5.3, and research quality evaluation was conducted with the modified Jadad scale. Results Fourteen studies, with 798 individuals related to the intervention of Tai chi on diabetes, were included. The results showed that, compared with nonexercise, Tai chi had the effect of lowering fasting blood glucose [MD = −1.39, 95% CI (−1.95, −0.84), P < 0.0001] and the subgroup effect size decreased with the increase of total exercise amount, there is no significant difference between Tai chi and other aerobic exercises [MD = −0.50, 95% CI (−1.02, 0.02), P = 0.06]; compared with nonexercise, Tai chi could reduce HbA1c [MD = −0.21, 95% CI (−0.61, 0.19), P = 0.31], and the group effect size decreased with the increase of total exercise amount. The reducing HbA1c effect of Tai chi was better than that of other aerobic exercises, but the difference was at the margin of statistical significance [MD = −0.19, 95% CI (−0.37, 0.00), P = 0.05]; compared with nonexercise, Tai chi had the effect of reducing 2 h postprandial blood glucose [MD = −2.07, 95% CI (−2.89, −1.26), P = 0.0002], there is no significant difference between Tai chi and other aerobic exercises in reducing 2 h postprandial blood glucose [MD = −0.44, 95% CI (−1.42, 0.54), P = 0.38]. Conclusion Tai chi can effectively affect the management of blood glucose and HbA1c in type-2 DM patients. Long-term adherence to Tai chi has a better role in reducing blood glucose and HbA1c levels in type 2 DM patients.
... According to the global burden of disease report, DM caused 1.37 million deaths in 2017 and has become the third largest noncommunicable disease threatening human health throughout the world, which is second only to cancer and cardiovascular diseases [3][4][5]. At present, in terms of the cost of diabetes treatment, the economic cost is high, with an amount reaching 20.86 billion, which accounts for 4.38% of the total medical cost; this situation has caused a considerable economic burden on individuals, families, and society [6,7]. Increasing evidence has indicated that abnormalities in pancreatic islets, especially pancreatic β-cells, may be the central link in the onset of T2DM [8]. ...
Article
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Objective: Type 2 diabetes mellitus (T2DM) is a chronic disease characterized by chronic hyperglycemia, which is also accompanied by changes in blood lipids and protein. According to research reports, Ginseng-plus-Bai-Hu-Tang (GBHT) has significant antihyperglycemic activity. Nevertheless, the evidence of effectiveness is not enough. In order to verify the effectiveness and safety of GBHT combined with conventional Western medicine (CWM) in the treatment of T2DM, we carried out this meta-analysis. Method: We collected 7 electronic databases from the inception to September 1, 2021; then, 12 studies were selected. The data analysis and methodological evaluation were conducted by the software RevMan 5.3.3 and Stata 12.0. Results: The meta-analysis revealed that when GBHT was adopted in combination with CWM, the effective rate (OR = 2.98, 95% CI = [2.01, 4.43], P < 0.00001), the FBG (MD = -0.86, 95% CI = [-1.06, -0.65], P < 0.00001), 2hBG (MD = -0.80, 95% CI = [-1.05, -0.55], P < 0.00001), and HbA1c (MD = -0.64, 95% CI = [-0.98, -0.30], P = 0.0002) of T2DM patients improved significantly compared with the control group. After GBHT combined with CWM treatment, HOME-RI (MD = -0.75, 95% CI = [-1.38, -0.12] P = 0.02) of T2DM patients was superior to CWM alone. In comparison, the benefit from FINS (MD = -1.42, 95% CI = [-4.46, -1.62], P = 0.36) was not apparent. In addition, none of the adverse events mentioned occurred, indicating that it is safe enough. Conclusion: GBHT combined with CWM is an effective and safe as adjunctive treatment for patients with T2DM. Nevertheless, due to the limitation of the quality of the included studies, additional high-quality researches are required to further confirm these results.
... Despite the absence of data from African countries, it is expected that lower fasting glucose concentration cut-offs for HFDP diagnosis, in addition to increased awareness and improved screening as well as increasing calls for universal screening for HFDP, may result in a higher prevalence of HFDP worldwide, especially in transitioning populations, such as South Africa. In China, for example, a 4-fold increase in GDM prevalence was noted when universal screening was introduced [13]. ...
Article
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Background: Global data indicate that women with a history of hyperglycemia first detected in pregnancy (HFDP) are at up to 7 times risk of progressing to type 2 diabetes mellitus (T2DM) compared with their counterparts who have pregnancies that are not complicated by hyperglycemia. However, there are no data from the sub-Saharan African region, which has the highest projected rise in diabetes prevalence globally. The aim of this study was to determine the proportion of women who progress to T2DM and associated risk factors 5 to 6 years after HFDP in Cape Town, South Africa. Methods and findings: All women with HFDP, at a major referral hospital in Cape Town, were followed up 5 to 6 years later using a cross-sectional study. Each participant had a 75 g oral glucose tolerance test; anthropometric measurements and a survey were administered. A total of 220 participants were followed up. At this time, their mean age was 37.2 years (SD 6.0). Forty-eight percent (95% CI 41.2-54.4) progressed to T2DM, 5.5% (95% CI 3.1-9.4) had impaired fasting glucose, and 10.5% (95% CI 7.0-15.3) had impaired glucose tolerance. Of the participants who progressed to T2DM, 47% were unaware of their diabetes status. When HFDP was categorized post hoc according to WHO 2013 guidelines, progression in the diabetes in pregnancy (DIP) group was 81% (95% CI 70.2-89.0) and 31.3% (95% CI 24.4-39.3) in the gestational diabetes mellitus (GDM) category. Factors associated with risk of progression to T2DM were; at follow-up: waist circumference (odds ratios [OR] 1.1, 95% CI 1.0-1.1, p = 0.007), hip circumference (OR 0.9, 95% CI 0.8-1.0, p = 0.001), and BMI (OR 1.1, 95% CI 1.0-1.3, p = 0.001), and at baseline: insulin (OR 25.8, 95% CI 3.9-171.4, p = 0.001) and oral hypoglycaemic treatment during HFDP (OR 4.1, 95% CI 1.3-12.9, p = 0.018), fasting (OR 2.7, 95% CI 1.5-4.8, p = 0.001), and oral glucose tolerance test 2-hour glucose concentration at HFDP diagnosis (OR 4.3, 95% CI 2.4-7.7, p < 0.001). Our findings have limitations in that we did not include a control group of women without a history of HFDP. Conclusions: The progression to T2DM in women with previous HFDP found in this study highlights the need for interventions to delay or prevent progression to T2DM after HFDP. In addition, interventions to prevent HFDP may also contribute to reducing the risk of T2DM.
... In China, there also be a rapid increase in the prevalence of DM associated with recent economic development, and the current diabetic subjects were ∼113.9 million, and a further 493.4 million persons with prediabetes (Xu et al., 2013;Chan et al., 2014). And the type 2 DM that closely related to obesity is the main contributor to the increase of DM prevalence (Ma et al., 2017). ...
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Background: Diabetic cardiomyopathy (DCM) is considered to be a distinct clinical entity independent of concomitant macro- and microvascular disorders, which is initiated partly by disturbances in energy substrates. This study was to observe the dynamic modulations of berberine in DCM rats and explore the changes of lipidomic profiles of myocardial tissue. Methods: Sprague-Dawley (SD) rats were fed high-sucrose and high-fat diet (HSHFD) for totally 22 weeks and intraperitoneally (i.p.) injected with 30 mg/kg of streptozotocin (STZ) at the fifth week to induce DCM. Seventy-two hours after STZ injection, the rats were orally given with berberine at 10, 30 mg/kg and metformin at 200 mg/kg, respectively. Dynamic changes of cardiac function, heart mass ratios and blood lipids were observed at f 4, 10, 16, and 22, respectively. Furthermore, lipid metabolites in myocardial tissue at week 16 were profiled by the ultra-high-performance liquid chromatography coupled to a quadruple time of flight mass spectrometer (UPLC/Q-TOF/MS) approach. Results: Berberine could protect against cardiac diastolic and systolic dysfunctions, as well as cardiac hypertrophy, and the most effective duration is with 16-week of administration. Meanwhile, 17 potential biomarkers of phosphatidylcholines (PCs), phosphatidylethanolamines (PEs) and sphingolipids (SMs) of DCM induced by HSFD/STZ were identified. The perturbations of lipidomic profiles could be partly reversed with berberine intervention, i.e., PC (16:0/20:4), PC (18:2/0:0), PC (18:0/18:2), PC (18:0/22:5), PC (20:4/0:0), PC (20:4/18:0), PC (20:4/18:1), PC (20:4/20:2), PE (18:2/0:0), and SM (d18:0/16:0). Conclusions: These results indicated a close relationship between PCs, PEs and SMs and cardiac damage mechanisms during development of DCM. The therapeutic effects of berberine on DCM are partly caused by interferences with PCs, PEs, and SMs metabolisms.
Article
Early identification of individuals at high risk of diabetes is crucial for implementing early intervention strategies. However, algorithms specific to elderly Chinese adults are lacking. The aim of this study is to build effective prediction models based on machine learning (ML) for the risk of type 2 diabetes mellitus (T2DM) in Chinese elderly. A retrospective cohort study was conducted using the health screening data of adults older than 65 years in Wuhan, China from 2018 to 2020. With a strict data filtration, 127,031 records from the eligible participants were utilized. Overall, 8298 participants were diagnosed with incident T2DM during the 2-year follow-up (2019–2020). The dataset was randomly split into training set (n = 101,625) and test set (n = 25,406). We developed prediction models based on four ML algorithms: logistic regression (LR), decision tree (DT), random forest (RF), and extreme gradient boosting (XGBoost). Using LASSO regression, 21 prediction features were selected. The Random under-sampling (RUS) was applied to address the class imbalance, and the Shapley Additive Explanations (SHAP) was used to calculate and visualize feature importance. Model performance was evaluated by the area under the receiver operating characteristic curve (AUC), sensitivity, specificity, and accuracy. The XGBoost model achieved the best performance (AUC = 0.7805, sensitivity = 0.6452, specificity = 0.7577, accuracy = 0.7503). Fasting plasma glucose (FPG), education, exercise, gender, and waist circumference (WC) were the top five important predictors. This study showed that XGBoost model can be applied to screen individuals at high risk of T2DM in the early phrase, which has the strong potential for intelligent prevention and control of diabetes. The key features could also be useful for developing targeted diabetes prevention interventions.
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The design of one-dimensional semiconductor metal oxides (SMOs) with porous structure has attracted tremendous attention owing to their larger specific surface area and a greater number of surface-active sites. Herein, [email protected]3-SnO2 nanofibers were fabricated through post-synthetic hydrothermal treatment which employed self-assembly A-stage phenolic resin as a sacrificial template. The nanopores observed in the [email protected]3-SnO2 nanofibers had diameters of about 3.5 nm. The nanoporous WO3-SnO2 nanofibers with well-dispersed tungsten species, exhibit excellent sensing performance, even at parts per billion level concentrations of gases. In a comparison with [email protected]2 sample, the [email protected]3-SnO2 nanofibers exhibited a five times higher response (S = 79.6) to 0.5 ppm acetone at 150 °C and a good acetone selectivity. Furthermore, the [email protected]3-SnO2 nanofibers-based sensor also possessed good long-term stability. The extraordinary sensing performance can be attributed to the porous structure, highly one-dimensional interconnection, larger specific surface area, and WO3/SnO2 heterostructure. The approach proposed for functionalized WO3-SnO2 nanofibers in this work may contribute to the potential application in human health breath analysis by non-invasive detection.
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Breastfeeding promotion is facing many challenges around the world. Unfortunately, in many countries of the Eastern Mediterranean region (EMR), exclusive breastfeeding (EBF) and continued breastfeeding rates are low and continue to decline. These rates are challenged by the complex emergency situations many countries in the region are facing
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The consumption of alcohol during pregnancy is frequent despite clear guidelines that indicate that abstinence is the safest option to prevent adverse offspring outcomes. These outcomes range from overt craniofacial abnormalities through to outcomes such as mental illness, hyperactivity and social difficulties. Human and animal studies have demonstrated that these neurological outcomes may be due to impaired function of the hypothalamic-pituitary-adrenal axis (HPA) in offspring, resulting in altered basal glucocorticoid tone and disrupted responsiveness to stress. However, little is known of the impact of alcohol consumption around the time of conception, known as the periconceptional period, on offspring HPA function. Therefore, this study aimed to use a well-established rat model of ethanol consumption during the periconceptional period (PC:EtOH) to investigate offspring HPA activity, including behaviours, stress responsiveness and underlying molecular pathways. As alcohol consumption directly alters HPA function, this study also aimed to examine if PC:EtOH exposure impairs maternal HPA activity and related physiological pathways, including renal and metabolic function. Female Sprague-Dawley rats were treated with PC:EtOH (12.5% v/v EtOH liquid diet) or a control diet from 4 days before conception, until embryonic day (E) 4. Behavioural tests were performed on offspring at three months of age to assess mental illness-like phenotypes (utilising the Forced Swim Test [FST] and Social Interaction [SI] paradigm), and at five months of age, HPA reactivity tests (combined dexamethasone suppression test [DST] and corticotropin-releasing hormone stimulation test [CST] and restraint stress) were performed. In a separate study, basal corticosterone concentrations were measured at 6 months, and adrenal glands were collected for analysis of steroidogenic gene expression. Aged cohorts (12-14 months) were utilised to measure basal plasma corticosterone, followed by the collection of adrenal glands, pituitary glands, hypothalamus and hippocampal tissue for analysis of various steroidogenesis and glucocorticoid signalling genes and pathology. In a separate cohort of aged rats, telemetry was used to asses blood pressure, heart rate and plasma corticosterone concentrations during 30-minute restraint stress. Maternal hormones (corticosterone, aldosterone), renal function and plasma glucose and lipids were assessed at various stages in gestation. Adrenal glands were collected from dams at E5, E15 and E20 for analysis of steroidogenic gene expression. Placental samples were collected at E20 and genes expression of the glucocorticoid (Nr3c1) and corticotrophin hormone receptor (Crh-r1) measured. 3 | P a g e This study revealed that PC:EtOH exposure resulted in altered offspring behavioural outcomes, including increased depressive-like behaviour in the forced swim test and altered social interaction with a novel rat. Adult offspring also demonstrated HPA hyperactivity, with elevated responses to the DST/CST challenge. Although there was no difference observed in adult offspring, aged PC:EtOH female offspring demonstrated an altered response to restraint, with reduced stress-induced plasma corticosterone and pressor response. Interestingly, PC:EtOH exposure also resulted in reduced basal plasma corticosterone concentrations in adult and aged female but not male offspring. Furthermore, female offspring showed pituitary gland abnormalities and increased mRNA for Nr3c1 and heat shock protein 90 (Hsp901a) in the hippocampus, suggesting altered HPA signalling and regulatory pathways. Adrenal and hypothalamic mRNA expression of genes regulating glucocorticoid production were not overtly altered by PC:EtOH in aged offspring. PC:EtOH significantly increased plasma corticosterone in the dam prior to mating (E-2). During pregnancy, PC:EtOH resulted in lower concentrations at E5, no differences at E15, and an increase at E20. Only minor changes in the expression of genes which regulate adrenal steroidogenesis were observed in PC:EtOH dams at E5 and E15, with the latter likely to have contributed to the observed increase in plasma corticosterone at E20. PC:EtOH had no impact on metabolic parameters (high and low-density lipoproteins and triglycerides) or renal function (food, water, urinary flow and renal electrolytes) in late gestation. However, placental markers of glucocorticoid exposure were elevated in response to exposure. This study supports the hypothesis that periconceptional ethanol exposure alters the HPA of the mother and programs sex-specific alterations in offspring in a rat model. Maternal HPA and related physiological changes as a consequence of PC:EtOH is likely to contribute to the HPA hyperresponsiveness, and underlie behavioural outcomes observed in this study. Furthermore, these changes to the HPA may be independent of the adrenal gland, with central regulatory pathways involving the hippocampus altered by PC:EtOH. This thesis has provided novel and important evidence that alcohol exposure around the time of conception impairs offspring mental-health like outcomes and induces HPA dysregulation. This work reinforces the concept that the maternal stress axis is highly sensitive to perturbations during early pregnancy. As this system is critical in many major physiological pathways, this can have significant long-term disease implications for both the mother and the child, supporting the critical need for education of appropriate health and wellbeing in preparation for pregnancy.
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South Asians are at increased risk for developing type 2 diabetes and cardiovascular disease at lower BMI compared to other ancestral groups. Many factors contribute to this increased risk, including genetics, maternal‐fetal factors, diet, fitness, body composition, and unique pathophysiology. Increased cardiometabolic risk is also seen at younger ages in South Asian individuals as compared to their White counterparts. This risk persists in migrant communities outside of South Asia. With the growing prevalence of obesity, diabetes, and cardiovascular disease in the South Asian population, it is imperative that we better understand the mechanisms underlying this increased risk and implement strategies to address this growing public health problem during childhood and adolescence. This article is protected by copyright. All rights reserved.
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Ronald Ma and co-authors discuss Emma Norrman and colleagues' accompanying research study on the health of children born with assisted reproductive technology.
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There is a global burden of type 2 diabetes (T2DM), and the predicted escalation in its prevalence will be acutely felt by India and China. It was timely to seek the opinions of the key researchers in these countries and from around the world, so we may benefit from their understanding of the developmental, environmental and lifestyle factors that are pertinent to the disease.
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Context Obesity and diabetes are epidemic in the European Union (EU). Exposure to endocrine-disrupting chemicals (EDCs) is increasingly recognized as a contributor, independent of diet and physical activity. Objective The objective was to estimate obesity, diabetes, and associated costs that can be reasonably attributed to EDC exposures in the EU. Design An expert panel evaluated evidence for probability of causation using weight-of-evidence characterization adapted from that applied by the Intergovernmental Panel on Climate Change. Exposure-response relationships and reference levels were evaluated for relevant EDCs, and biomarker data were organized from peer-reviewed studies to represent European exposure and burden of disease. Cost estimation as of 2010 utilized published cost estimates for childhood obesity, adult obesity, and adult diabetes. Setting, Patients and Participants, and Intervention Cost estimation was performed from the societal perspective. Results The panel identified a 40% to 69% probability of dichlorodiphenyldichloroethylene causing 1555 cases of overweight at age 10 (sensitivity analysis: 1555–5463) in 2010 with associated costs of €24.6 million (sensitivity analysis: €24.6–86.4 million). A 20% to 39% probability was identified for dichlorodiphenyldichloroethylene causing 28 200 cases of adult diabetes (sensitivity analysis: 28 200–56 400) with associated costs of €835 million (sensitivity analysis: €835 million–16.6 billion). The panel also identified a 40% to 69% probability of phthalate exposure causing 53 900 cases of obesity in older women and €15.6 billion in associated costs. Phthalate exposure was also found to have a 40% to 69% probability of causing 20 500 new-onset cases of diabetes in older women with €607 million in associated costs. Prenatal bisphenol A exposure was identified to have a 20% to 69% probability of causing 42 400 cases of childhood obesity, with associated lifetime costs of €1.54 billion. Conclusions EDC exposures in the EU contribute substantially to obesity and diabetes, with a moderate probability of >€18 billion costs per year. This is a conservative estimate; the results emphasize the need to control EDC exposures.
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Purpose: The association between famine exposure (defined as lengthy and continuous deprivation of food) during early life and type 2 diabetes (T2DM) in adulthood remains controversial. A meta-analysis was performed to better clarify the relation of famine exposure to later T2DM risk. Methods: A systematic literature search was performed in PubMed, Web of Science, Embase and China National Knowledge Infrastructure for relevant available articles. The articles were limited to those in English or Chinese from January 1990 to June 2016. Observational studies evaluating the association between famine exposure and T2DM were included. The pooled relative risk (RR) with 95% confidence interval (CI) was used to estimate the effect of famine exposure on T2DM. The I (2) was used to assess heterogeneity, and the random effects model (REM) was adopted as the pooling method. Results: We included 11 published articles with 12391 T2DM cases for this meta-analysis. A significant association of early life famine exposure with increased risk of T2DM was observed (RR = 1.38, 95% CI 1.17-1.63; I (2) = 63.4%; P heterogeneity = 0.002). Compared with the unexposed, the RRs of T2DM were 1.36 (95% CI 1.12-1.65) for fetal-infant exposed and 1.40 (95% CI 0.98-1.99) for childhood exposed. After excluding one article that had a strong effect on heterogeneity, the pooled RR was 1.46 (95% CI 1.27-1.69). Conclusion: The meta-analysis indicates that famine exposure during early life especially fetal-infant exposure may increase the risk of T2DM in adulthood. Measures should be taken to prevent malnutrition during important stages of growth and development to reduce the prevalence of T2DM.
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Background: There has been increased recognition that prenatal or perinatal nutrition has an effect on the development of type 2 diabetes (T2D) in adulthood, although studies that have directly examined whether the effect could be transmitted to the next generation remain sparse. Objective: We investigated the role of prenatal exposure to the Chinese famine in affecting future T2D risk in adulthood in 2 consecutive generations. Design: A total of 1034 families, including 2068 parents [parental generation (F1)] and 1183 offspring [offspring generation (F2)], were recruited from the Suihua rural area that was affected by the Chinese Famine of 1959-1961. Participants born between 1 October 1959 and 30 September 1961 were defined as famine exposed, and those born between 1 October 1962 and 30 September 1964 were defined as nonexposed. The F2 were classified as having 1) no parent exposed to famine, 2) only a mother exposed to famine, 3) only a father exposed to famine, or 4) both parents exposed to famine. Classical risk factors for T2D as well as fasting-glucose- and oral-glucose-tolerance tests were measured in both the F1 and F2. Results: Prenatal exposure to famine was associated with elevated risks of hyperglycemia (multivariable-adjusted OR: 1.93; 95% CI: 1.51, 2.48) and T2D (OR: 1.75; 95% CI: 1.20, 2.54) in adulthood in F1. Furthermore, compared with the offspring of nonexposed parents, the F2 with exposed parents- especially both exposed parents-had increased hyperglycemia risk (OR: 2.02; 95% CI: 1.12, 3.66) in adulthood. Conclusion: Prenatal exposure to famine remarkably increases hyperglycemia risk in 2 consecutive generations of Chinese adults independent of known T2D risk factors, which supports the notion that prenatal nutrition plays an important role in the development of T2D across consecutive generations of Chinese adults. This trial was registered at www.chictr.org.cn as ChiCTR-ECH-13003644.
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Background: Consistent evidence of an influence of maternal dietary intake during pregnancy on infant body size and composition in human populations is lacking, despite robust evidence in animal models. Objective: We sought to evaluate the influence of maternal macronutrient intake and balance during pregnancy on neonatal body size and composition, including fat mass and fat-free mass. Study design: The analysis was conducted among 1040 mother-offspring pairs enrolled in the prospective prebirth observational cohort: the Healthy Start Study. Diet during pregnancy was collected using repeated 24-hour dietary recalls (up to 8). Direct measures of body composition were obtained using air displacement plethysmography. The National Cancer Institute measurement error model was used to estimate usual dietary intake during pregnancy. Multivariable partition (nonisocaloric) and nutrient density (isocaloric) linear regression models were used to test the associations between maternal dietary intake and neonatal body composition. Results: The median macronutrient composition during pregnancy was 32.2% from fat, 15.0% from protein, and 47.8% from carbohydrates. In the partition multivariate regression model, individual macronutrient intake values were not associated with birthweight or fat-free mass, but were associated with fat mass. Respectively, 418 kJ increases in total fat, saturated fat, unsaturated fat, and total carbohydrates were associated with 4.2-g (P = .03), 11.1-g (P = .003), 5.9-g (P = .04), and 2.9-g (P = .02) increases in neonatal fat mass, independent of prepregnancy body mass index. In the nutrient density multivariate regression model, macronutrient balance was not associated with fat mass, fat-free mass, or birthweight after adjustment for prepregnancy body mass index. Conclusion: Neonatal adiposity, but not birthweight, is independently associated with increased maternal intake of total fat, saturated fat, unsaturated fat, and total carbohydrates, but not protein, suggesting that most forms of increased caloric intake contribute to fetal fat accretion.
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Background and objective: Poor maternal diet in pregnancy can influence fetal growth and development. We tested the hypothesis that poor maternal diet quality during pregnancy would increase neonatal adiposity (percent fat mass, %FM) at birth by increasing the fat mass (FM) component of neonatal body composition. Methods: Our analysis was conducted using a pre-birth observational cohort of 1079 mother-offspring pairs. Pregnancy diet was assessed via repeated Automated Self-Administered 24-hour dietary recalls, from which Healthy Eating Index-2010 (HEI-2010) scores were calculated for each mother. HEI-2010 was dichotomized into scores ⩽57 and scores >57, with low scores representing poorer diet quality. Neonatal %FM was assessed within 72 h after birth with air displacement plethysmography. Using univariate and multivariate linear models, we analyzed the relationship between maternal diet quality and neonatal %FM, FM, and fat-free mass (FFM) while adjusting for pre-pregnancy body mass index (BMI), physical activity, maternal age, smoking, daily energy intake, preeclampsia, hypertension, infant sex, and gestational age. Results: Total HEI-2010 score ranged between 18.2 and 89.5 (mean: 54.2, s.d.: 13.6). An HEI-2010 score ⩽57 was significantly associated with higher neonatal %FM (β=0.58, 95% CI 0.07, 1.1, P<0.05) and FM (β=20.74; 95% CI 1.49, 40.0; P<0.05) but no difference in FFM. Conclusions: Poor diet quality during pregnancy increases neonatal adiposity independent of maternal pre-pregnancy BMI and total caloric intake. This further implicates maternal diet as a potentially important exposure for fetal adiposity.International Journal of Obesity accepted article preview online, 02 May 2016. doi:10.1038/ijo.2016.79.
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Study question What has been the effect on purchases of beverages from stores in Mexico one year after implementation of the excise tax on sugar sweetened beverages? Methods In this observational study the authors used data on the purchase of beverages in Mexico from January 2012 to December 2014 from an unbalanced panel of 6253 households providing 205 112 observations in 53 cities with more than 50 000 inhabitants. To test whether the post-tax trend in purchases was significantly different from the pretax trend, the authors used a difference in difference fixed effects model, which adjusts for both macroeconomic variables that can affect the purchase of beverages over time, and pre-existing trends. The variables used in the analysis included demographic information on household composition (age and sex of household members) and socioeconomic status (low, middle, and high). The authors compared the predicted volumes (mL/capita/day) of taxed and untaxed beverages purchased in 2014—the observed post-tax period—with the estimated volumes that would have been purchased if the tax had not been implemented (counterfactual) based on pretax trends. Study answer and limitations Relative to the counterfactual in 2014, purchases of taxed beverages decreased by an average of 6% (−12 mL/capita/day), and decreased at an increasing rate up to a 12% decline by December 2014. All three socioeconomic groups reduced purchases of taxed beverages, but reductions were higher among the households of low socioeconomic status, averaging a 9% decline during 2014, and up to a 17% decrease by December 2014 compared with pretax trends. Purchases of untaxed beverages were 4% (36 mL/capita/day) higher than the counterfactual, mainly driven by an increase in purchases of bottled plain water. What this study adds The tax on sugar sweetened beverages was associated with reductions in purchases of taxed beverages and increases in purchases of untaxed beverages. Continued monitoring is needed to understand purchases longer term, potential substitutions, and health implications. Funding, competing interests, data sharing This work was supported by grants from Bloomberg Philanthropies and the Robert Wood Johnson Foundation and by the Instituto Nacional de Salud Pública and the Carolina Population Center. The authors have no competing interests. No additional data are available.
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Objectives: To assess if the maternal pre-pregnancy weight status (MPWS) alters the association of early infant feeding pattern (at one and third months) with infant body mass index (BMI) in the first two years of life. Methods: A cohort of 2,220 neonates were recruited in a community-based study conducted in China. Body weight and length were measured at birth, at age one and two, with BMI calculated accordingly. The BMI z-scores (BMI-Z) were computed according to the World Health Organization Growth Standard (2006). Feeding patterns were classified as exclusive breastfeeding (EBF), mixed feeding (MF), and formula feeding (FF). General linear models (GLM) were employed to estimate main and interaction effects of EBF and MPWS on children's BMI-Z. Results: No main effect of MPWS was found on child BMI-Z at ages one and two, nor the feeding patterns. An interaction between MPWS and feeding patterns was detected (p<0.05). For children who were formula fed during the first month, those who were born to overweight/obesity (OW/OB) mothers had a significantly greater BMI-Z at ages one and two, compared with those with underweight/normal weight (UW/NW) mothers. FF children had greater BMI-Z at ages one and two compared with their EBF and MF counterparts, when they were born to OW/OB mothers. Conclusions: Maternal pre-pregnancy weight control and early initiation of EBF for children are essential for healthy development in children's BMI, hence the prevention of early life obesity.
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Evidence suggests that excessive intake of added sugars has adverse effects on cardiometabolic health, which is consistent with many reviews and consensus reports from WHO and other unbiased sources. 74% of products in the US food supply contain caloric or low-calorie sweeteners, or both. Of all packaged foods and beverages purchased by a nationally representative sample of US households in 2013, 68% (by proportion of calories) contain caloric sweeteners and 2% contain low-calorie sweeteners. We believe that in the absence of intervention, the rest of the world will move towards this pervasiveness of added sugars in the food supply. Our analysis of trends in sales of sugar-sweetened beverages around the world, in terms of calories sold per person per day and volume sold per person per day, shows that the four regions with the highest consumption are North America, Latin America, Australasia, and western Europe. The fastest absolute growth in sales of sugar-sweetened beverages by country in 2009-14 was seen in Chile. We believe that action is needed to tackle the high levels and continuing growth in sales of such beverages worldwide. Many governments have initiated actions to reduce consumption of sugar-sweetened beverages in the past few years, including taxation (eg, in Mexico); reduction of their availability in schools; restrictions on marketing of sugary foods to children; public awareness campaigns; and positive and negative front-of-pack labelling. In our opinion, evidence of the effectiveness of these actions shows that they are moving in the right direction, but governments should view them as a learning process and improve their design over time. A key challenge for policy makers and researchers is the absence of a consensus on the relation of beverages containing low-calorie sweeteners and fruit juices with cardiometabolic outcomes, since decisions about whether these are healthy substitutes for sugar-sweetened beverages are an integral part of policy design.
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Background: Lactation improves glucose metabolism, but its role in preventing type 2 diabetes mellitus (DM) after gestational diabetes mellitus (GDM) remains uncertain. Objective: To evaluate lactation and the 2-year incidence of DM after GDM pregnancy. Design: Prospective, observational cohort of women with recent GDM. (ClinicalTrials.gov: NCT01967030). Setting: Integrated health care system. Participants: 1035 women diagnosed with GDM who delivered singletons at 35 weeks' gestation or later and enrolled in the Study of Women, Infant Feeding and Type 2 Diabetes After GDM Pregnancy from 2008 to 2011. Measurements: Three in-person research examinations from 6 to 9 weeks after delivery (baseline) and annual follow-up for 2 years that included 2-hour, 75-g oral glucose tolerance testing; anthropometry; and interviews. Multivariable Weibull regression models evaluated independent associations of lactation measures with incident DM adjusted for potential confounders. Results: Of 1010 women without diabetes at baseline, 959 (95%) were evaluated up to 2 years later; 113 (11.8%) developed incident DM. There were graded inverse associations for lactation intensity at baseline with incident DM and adjusted hazard ratios of 0.64, 0.54, and 0.46 for mostly formula or mixed/inconsistent, mostly lactation, and exclusive lactation versus exclusive formula feeding, respectively (P trend = 0.016). Time-dependent lactation duration showed graded inverse associations with incident DM and adjusted hazard ratios of 0.55, 0.50, and 0.43 for greater than 2 to 5 months, greater than 5 to 10 months, and greater than 10 months, respectively, versus 0 to 2 months (P trend = 0.007). Weight change slightly attenuated hazard ratios. Limitation: Randomized design is not feasible or desirable for clinical studies of lactation. Conclusion: Higher lactation intensity and longer duration were independently associated with lower 2-year incidences of DM after GDM pregnancy. Lactation may prevent DM after GDM delivery. Primary funding source: National Institute of Child Health and Human Development.
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Obesity during pregnancy is associated with an increased risk of short- and long-term metabolic dysfunction in the mother and her offspring. Both higher maternal pregravid body mass index (kg m(-)(2)) and excessive gestational weight gain (GWG) have been associated with adverse pregnancy outcomes such as gestational diabetes, preeclampsia and fetal adiposity. Multiple lifestyle intervention trials consisting of weight management using various diets, increased physical activity and behavioral modification techniques have been employed to avoid excessive GWG and improve perinatal outcomes. These randomized controlled trials (RCTs) have achieved modest success in decreasing excessive GWG, although the decrease in GWG was often not within the current Institute of Medicine guidelines. RCTs have generally not had any success with decreasing the risk of maternal gestational diabetes (GDM), preeclampsia or excessive fetal growth often referred to as macrosomia. Although the lack of success for these trials has been attributed to lack of statistical power and poor compliance with study protocols, our own research suggests that maternal pregravid and early pregnancy metabolic condition programs early placenta function and gene expression. These alterations in maternal/placental function occur in the first trimester of pregnancy prior to when most intervention trials are initiated. For example, maternal accrural of adipose tissue relies on prior activation of genes controlling lipogenesis and low-grade inflammation in early pregnancy. These metabolic alterations occur prior to any changes in maternal phenotype. Therefore, trials of lifestyle interventions before pregnancy are needed to demonstrate the safety and efficacy for both the mother and her offspring.International Journal of Obesity advance online publication, 17 March 2015; doi:10.1038/ijo.2015.15.
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Context: Obesity and diabetes are epidemic in the European Union (EU). Exposure to endocrine-disrupting chemicals (EDCs) is increasingly recognized as a contributor, independent of diet and physical activity. Objective: The objective was to estimate obesity, diabetes, and associated costs that can be reasonably attributed to EDC exposures in the EU. Design: An expert panel evaluated evidence for probability of causation using weight-of-evidence characterization adapted from that applied by the Intergovernmental Panel on Climate Change. Exposure-response relationships and reference levels were evaluated for relevant EDCs, and biomarker data were organized from peer-reviewed studies to represent European exposure and burden of disease. Cost estimation as of 2010 utilized published cost estimates for childhood obesity, adult obesity, and adult diabetes. Setting, Patients and Participants, and Intervention: Cost estimation was performed from the societal perspective. Results: The panel identified a 40% to 69% probability of dichlorodiphenyldichloroethylene causing 1555 cases of overweight at age 10 (sensitivity analysis: 1555-5463) in 2010 with associated costs of €24.6 million (sensitivity analysis: €24.6-86.4 million). A 20% to 39% probability was identified for dichlorodiphenyldichloroethylene causing 28 200 cases of adult diabetes (sensitivity analysis: 28 200-56 400) with associated costs of €835 million (sensitivity analysis: €835 million-16.6 billion). The panel also identified a 40% to 69% probability of phthalate exposure causing 53 900 cases of obesity in older women and €15.6 billion in associated costs. Phthalate exposure was also found to have a 40% to 69% probability of causing 20 500 new-onset cases of diabetes in older women with €607 million in associated costs. Prenatal bisphenol A exposure was identified to have a 20% to 69% probability of causing 42 400 cases of childhood obesity, with associated lifetime costs of €1.54 billion. Conclusions: EDC exposures in the EU contribute substantially to obesity and diabetes, with a moderate probability of >€18 billion costs per year. This is a conservative estimate; the results emphasize the need to control EDC exposures.
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The increase in childhood obesity is a serious public health concern. Several studies have indicated that breastfed children have a lower risk of childhood obesity than those who were not breastfed, while other studies have provided conflicting evidence. The objective of this meta-analysis was to investigate the association between breastfeeding and the risk of childhood obesity. The PubMed, EMBASE and CINAHL Plus with Full Text databases were systematically searched from start date to 1st August 2014. Based on the meta-analysis, pooled adjusted odds ratio (AOR) and 95% confidence interval (CI) were calculated. I2 statistic was used to evaluate the between-study heterogeneity. Funnel plots and Fail-safe N were used to assess publication bias and reliability of results, and results from both Egger test and Begg test were reported. Twenty-five studies with a total of 226,508 participants were included in this meta-analysis. The studies' publication dates ranged from 1997 to 2014, and they examined the population of 12 countries. Results showed that breastfeeding was associated with a significantly reduced risk of obesity in children (AOR = 0.78; 95% CI: 0.74, 0.81). Categorical analysis of 17 studies revealed a dose-response effect between breastfeeding duration and reduced risk of childhood obesity. Results of our meta-analysis suggest that breastfeeding is a significant protective factor against obesity in children.
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Non-caloric artificial sweeteners (NAS) are among the most widely used food additives worldwide, regularly consumed by lean and obese individuals alike. NAS consumption is considered safe and beneficial owing to their low caloric content, yet supporting scientific data remain sparse and controversial. Here we demonstrate that consumption of commonly used NAS formulations drives the development of glucose intolerance through induction of compositional and functional alterations to the intestinal microbiota. These NAS-mediated deleterious metabolic effects are abrogated by antibiotic treatment, and are fully transferrable to germ-free mice upon faecal transplantation of microbiota configurations from NAS-consuming mice, or of microbiota anaerobically incubated in the presence of NAS. We identify NAS-altered microbial metabolic pathways that are linked to host susceptibility to metabolic disease, and demonstrate similar NAS-induced dysbiosis and glucose intolerance in healthy human subjects. Collectively, our results link NAS consumption, dysbiosis and metabolic abnormalities, thereby calling for a reassessment of massive NAS usage.
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While outdoor physical activity has been shown to promote health and well-being,1 ,2 exercising in environments with high levels of air pollution can increase the risk of health problems ranging from asthma attacks to heart or lung pathologies.3 ,4 The interaction of these two phenomena is of specific significance in China, where outdoor physical activity has been a traditional practice but where rapid industrialisation has led to major degradation of the environment. This situation raises the spectre of an emergent major public health crisis in the most populous country in the world. There is clear and compelling evidence that regular physical activity produces substantial physical and mental health benefits, including improved health-related quality of life and decreased risk of premature morbidity and mortality.1 ,5 ,6 However, it is important to note that in contrast to the commodification of exercise in many western industrialised nations, where exercise for health is often carried out in indoor facilities such as fitness centres, the physical and mental health benefits of physical activity can be achieved outdoors in settings such as community green spaces, parks and trails.1 ,2 Therefore, public health policies designed to encourage participation in physical activity should focus on outdoor settings for promoting public health and improving overall quality of life,5–8 because outdoors settings can accommodate a much larger scale population involvement at substantially lower costs than can physical activity in indoor facilities. In China, cultural norms, history and public policy have presaged this logistical reality, with a significant portion of the population, especially in the older demographic, exercising daily in outdoor settings such as parks, village squares and along streets, through leisure walking, jogging, dancing, bicycling or Tai Ji Quan.9–11 Studies in China have shown a positive association between traditional …
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Noncommunicable chronic diseases have become the leading causes of mortality and disease burden worldwide. To investigate the prevalence of diabetes and glycemic control in the Chinese adult population. Using a complex, multistage, probability sampling design, we conducted a cross-sectional survey in a nationally representative sample of 98,658 Chinese adults in 2010. Plasma glucose and hemoglobin A1c levels were measured after at least a 10-hour overnight fast among all study participants, and a 2-hour oral glucose tolerance test was conducted among participants without a self-reported history of diagnosed diabetes. Diabetes and prediabetes were defined according to the 2010 American Diabetes Association criteria; whereas, a hemoglobin A1c level of <7.0% was considered adequate glycemic control. The overall prevalence of diabetes was estimated to be 11.6% (95% CI, 11.3%-11.8%) in the Chinese adult population. The prevalence among men was 12.1% (95% CI, 11.7%-12.5%) and among women was 11.0% (95% CI, 10.7%-11.4%). The prevalence of previously diagnosed diabetes was estimated to be 3.5% (95% CI, 3.4%-3.6%) in the Chinese population: 3.6% (95% CI, 3.4%-3.8%) in men and 3.4% (95% CI, 3.2%-3.5%) in women. The prevalence of undiagnosed diabetes was 8.1% (95% CI, 7.9%-8.3%) in the Chinese population: 8.5% (95% CI, 8.2%-8.8%) in men and 7.7% (95% CI, 7.4%-8.0%) in women. In addition, the prevalence of prediabetes was estimated to be 50.1% (95% CI, 49.7%-50.6%) in Chinese adults: 52.1% (95% CI, 51.5%-52.7%) in men and 48.1% (95% CI, 47.6%-48.7%) in women. The prevalence of diabetes was higher in older age groups, in urban residents, and in persons living in economically developed regions. Among patients with diabetes, only 25.8% (95% CI, 24.9%-26.8%) received treatment for diabetes, and only 39.7% (95% CI, 37.6%-41.8%) of those treated had adequate glycemic control. The estimated prevalence of diabetes among a representative sample of Chinese adults was 11.6% and the prevalence of prediabetes was 50.1%. Projections based on sample weighting suggest this may represent up to 113.9 million Chinese adults with diabetes and 493.4 million with prediabetes. These findings indicate the importance of diabetes as a public health problem in China.
Article
Objective: The objective of this study was to evaluate the effect of maternal hyperglycemia during pregnancy on cardiometabolic risk in offspring during early childhood. Research design and methods: A total of 970 mothers who had joined the Hyperglycemia and Adverse Pregnancy Outcome study were reevaluated, together with their child born during the study period, 7 years after delivery. Results: Offspring born to mothers diagnosed with gestational diabetes mellitus (GDM), as defined by World Health Organization 2013, had higher rates of abnormal glucose tolerance (4.7% vs 1.7%; P = 0.04), overweight or obesity, greater BMI, higher blood pressure (BP), lower oral disposition index, and a trend toward reduced β-cell function, than those born to mothers without GDM. For each SD increase in maternal fasting, 1-h, and 2-h glucose levels on oral glucose tolerance tests (OGTTs) between 24 and 32 weeks of the index pregnancy, the risk of abnormal glucose tolerance in the offspring showed a corresponding increase (adjusted odds ratio [OR] 1.85-2.00). The associations were independent of BMI before pregnancy, childhood obesity, or being born large for gestational age. The area under the curve for glucose levels during the five-point OGTT increased to a similar extent in boys and girls with each SD increase in maternal 1-h and 2-h plasma glucose on OGTTs during pregnancy. All three maternal glucose levels were also associated with increased adjusted odds ratios for childhood overweight or obesity, and adiposity among girls, but not boys. Conclusions: Maternal hyperglycemia in pregnancy is independently associated with offsprings' risk of abnormal glucose tolerance, obesity, and higher BP at 7 years of age. Its effect on childhood adiposity was apparent only in girls, not boys.
Article
Recent evidence demonstrates important maternal effects on an offspring's risk of developing metabolic disease. These effects extend across the full range of maternal environments and partly involve epigenetic mechanisms. The maternal effects can be explained in evolutionary terms, and there is some evidence for their transmission into succeeding generations. Unbalanced maternal diet or body composition, ranging from poor to rich environments, adversely influences the offspring's response to later challenges such as an obesogenic diet or physical inactivity, increasing the risk of disease. Adopting a life course approach that takes into account intergenerational effects has important implications for prevention of non-communicable diseases, particularly in populations undergoing rapid economic transition
Article
Context: In China, data on the prevalence of metabolic syndrome have been rare recently. Objective: The objective of the study was to evaluate the prevalence of metabolic syndrome and its components in 2010. Design, setting and participants: The study covered all 31 provinces of mainland China and consisted of a nationally representative population sample of 98,658 Chinese adults aged ≥ 18 years. Of these, 97,098 participants were eligible for the data analysis reported here. Main outcome measures: Estimates of the prevalence of metabolic syndrome and its components were calculated. To further explore whether metabolic syndrome is associated with the 10-year coronary heart disease risk, sex-stratified logistic regression models were used. Results: The prevalence of the metabolic syndrome was 33.9% (31.0% in men and 36.8% in women), which indicates that metabolic syndrome affects approximately 454 million adults in China. More than half of total adult population were suffering from low HDL-C and nearly half of participants have high blood pressure. Abdominal obesity and low HDL-C were more prevalent in women than in men, whereas high blood pressure, high blood glucose, and high triglycerides were more common in men. Metabolic syndrome was associated with a higher 10-year coronary heart disease risk after adjustment for potential risk factors and each component of metabolic syndrome as continuous variables. Conclusion: Our results showed a high prevalence of metabolic syndrome and its components in the general adult population in mainland China. Metabolic syndrome was independently associated with a higher 10-year risk of developing coronary heart disease.
Article
Background Breastfeeding is the gold standard for infant and young child feeding. Increased rates of breastfeeding could reduce morbidity and mortality for both children and mothers. In addition, breastfed children could have better cognitive development, persisting through later life. However, quantitative data are scarce on the effect of improved breastfeeding rates in China. The objectives of this study were to assess current breastfeeding rates and to analyse the potential effect of improved breastfeeding rates in China. Methods A national representative survey (Chinese Nutrition and Health Surveillance) of children ages 6 years was done in 2013. Stratified multistage cluster sampling was used to select study patricipants. WHO infant and young feeding indicators were used to assess breastfeeding practice. Lives Saved Tool (version 5·441) was used to estimate death prevented with improved breastfeeding practice. The survey was approved by the National Institute for Nutrition and Health, Chinese Center for Disease Control and Prevention Medical Ethnical Committee. All caregivers signed the consent form. Findings 14 539 children aged 2 years and younger (0–730 days) were studied from 55 counties in 30 provinces in China. The weighted prevalence for ever breastfed was 79·6%; 20·8% were exclusively breastfed at 6 months, 11·5% were breastfed at 1 year of age, and 6·9% were breastfed at 2 years of age. The median duration of breastfeeding was 8·63 months. Assuming an increase to 50% exclusively breastfed infants at 6 months, the Lives Saved Tool predicted 19 323 (11 266–22 530) fewer deaths and a reduction in mortality of 5% (from 10·7 per 1000 to 10·17 per 1000) among children under 5 years of age. Interpretation The rates of breastfeeding in China are low. Improved breastfeeding rates could be substantially reduce mortality in children aged 5 years and younger in China. Funding Chinese Central Government
Article
Prevention of obesity in women of reproductive age is widely recognised to be important both for their health and for that of their offspring. Weight-control interventions, including drug treatment, in pregnant women who are obese or overweight have not had sufficient impact on pregnancy and birth outcomes, which suggests that the focus for intervention should include preconception or post-partum periods. Further research is needed into the long-term effects of nutritional and lifestyle interventions before conception. To improve preconception health, an integrated approach, including pregnancy prevention, planning, and preparation is needed, involving more than the primary health-care sector and adopting an ecological approach to risk reduction that addresses personal, societal, and cultural influences. Raising awareness of the importance of good health in the period before pregnancy will require a new social movement: combining bottom-up mobilisation of individuals and communities with a top-down approach from policy initiatives. Interventions to reduce or prevent obesity before conception and during pregnancy could contribute substantially to achievement of the global Sustainable Development Goals, in terms of health, wellbeing, productivity, and equity in current and future generations.
Article
This study aimed to examine the effect of lifestyle intervention on the risk of gestational diabetes mellitus (GDM). We searched PubMed, Springer and other databases to retrieve articles published in English and Chinese up to 30 September 2015. The inclusion criteria were randomized controlled trials evaluating the effects of lifestyle intervention on risk of GDM. Exclusion criteria were studies with prepregnancy diabetes mellitus or interventions with nutrient supplements. Random-effect and fixed-effect model analyses were used to obtain pooled relative risks and 95% confidence intervals (CIs) of diet and physical activity on the risk of GDM. Subgroup analyses were performed to check the consistency of effect sizes across groups where appropriate. We identified 29 randomized controlled trials with 11,487 pregnant women, addressing the effect of lifestyle intervention on the risk of GDM. In the pooled analysis, either diet or physical activity resulted in an 18% (95%CI 5–30%) reduction in the risk of GDM (P = 0.0091). Subgroup analysis showed that such intervention was effective among women with intervention before the 15th gestational week (relative risk: 0.80, 95%CI 0.66–0.97), but not among women receiving the intervention afterwards. We conclude that lifestyle modification during pregnancy, especially before the 15th gestational week, can reduce the risk of GDM. © 2016 World Obesity
Article
Objective: The associations of maternal caffeine intake during pregnancy with offspring growth patterns and body fat and insulin levels at school age were examined. Methods: In a population-based birth cohort among 7,857 mothers and their children, maternal caffeine intake during pregnancy was assessed by questionnaires. Growth characteristics were measured from birth onward. At 6 years, body fat and insulin levels were measured. Results: Compared to children whose mothers consumed <2 units of caffeine per day during pregnancy (1 unit of caffeine is equivalent to 1 cup of coffee (90 mg caffeine)), those whose mothers consumed ≥6 units of caffeine per day tended to have a lower weight at birth, higher weight gain from birth to 6 years, and higher body mass index from 6 months to 6 years. Both children whose mothers consumed 4-5.9 and ≥6 units of caffeine per day during pregnancy tended to have a higher childhood body mass index and total body fat mass. Only children whose mothers consumed ≥6 units of caffeine per day had a higher android/gynoid fat mass ratio. Conclusions: These results suggest that high levels of maternal caffeine intake during pregnancy are associated with adverse offspring growth patterns and childhood body fat distribution.
Article
The last three decades have witnessed an epidemic rise in the number of peoplewith diabetes, especially type 2 diabetes, and particularly in developing countries, where more than 80% of the people with diabetes live. The rise of type 2 diabetes in South Asia is estimated to be more than 150% between 2000 and 2035. Although aging, urbanization, and associated lifestyle changes are the major determinants for the rapid increase, an adverse intrauterine environment and the resulting epigenetic changes could also contribute in many developing countries. The International Diabetes Federation estimated that there were 382 million people with diabetes in 2013, a number surpassing its earlier predictions.More than 60% of the people with diabetes live in Asia,with almost one-half in China and India combined. The Western Pacific, the world's most populous region, has more than 138.2 million people with diabetes, and the numbermay rise to 201.8 million by 2035. The scenario poses huge social and economic problems to most nations in the region and could impede national and, indeed, global development. More action is required to understand the drivers of the epidemic to provide a rationale for prevention strategies to address the rising global public health "tsunami." Unless drastic steps are taken through national prevention programs to curb the escalating trends in all of the countries, the social, economic, and health care challenges are likely to be insurmountable.
Article
Background The age of onset of type 2 diabetes is decreasing. Because non-Chinese patients with early-onset type 2 diabetes (defined here as diagnosis at <40 years) have increased risk of vascular complications, we investigated effects of early-onset versus late-onset type 2 diabetes on risk of non-fatal cardiovascular diseases in China. Methods We did a cross-sectional survey using data from the China National HbA1c Surveillance System (CNHSS), including 222 773 Chinese patients with type 2 diabetes in 630 hospitals from 106 cities in 30 provinces of China in 2012. We documented demographic information and clinical profiles. Non-fatal cardiovascular disease was defined as non-fatal coronary heart disease or non-fatal stroke. Prevalence of non-fatal cardiovascular diseases was standardised to the Chinese population in 2011. We did logistic regression analysis to obtain odds ratios (ORs) for the risk of cardiovascular disease in patients with early-onset versus late-onset type 2 diabetes. Because the CNHSS did not contain patients on diet or lifestyle treatment alone, and did not capture information on smoking or lipid or antihypertensive treatment, we validated our findings in another dataset from a cross-sectional, multicentre observational study (the 3B study) of outpatients with type 2 diabetes to confirm that exclusion of patients with diet treatment only and non-adjustment for lipid-lowering and antihypertensive drugs did not introduce major biases in the main analysis. Findings Of 222 773 patients recruited from April 1, 2012, to June 30, 2012, 24 316 (11%) had non-fatal cardiovascular disease. Patients with early-onset diabetes had a higher age-adjusted prevalence of non-fatal cardiovascular disease than did patients with late-onset diabetes (11•1% vs 4•9%; p<0•0001). After adjustment for age and sex, patients with early-onset type 2 diabetes had higher risk of non-fatal cardiovascular disease than did those with late-onset type 2 diabetes (OR 1•91, 95% CI 1•81–2•02). Adjustment for duration of diabetes greatly attenuated the effect size for risk of non-fatal cardiovascular disease (1•13, 1•06–1•20). Results of the validation study showed that exclusion of patients with diet only and non-adjustment for lipid-lowering and antihypertensive drugs resulted in marginal changes in ORs for risk of non-fatal cardiovascular disease in patients with early-onset versus late-onset type 2 diabetes. Early-onset type 2 diabetes remained associated with increased risk of cardiovascular disease, attributable to longer duration of diabetes. Interpretation Chinese patients with early-onset type 2 diabetes are at increased risk of non-fatal cardiovascular disease, mostly attributable to longer duration of diabetes. Funding Novo Nordisk China (for the China National HbA1c Surveillance System [CNHSS]) and Merck Sharp & Dohme China (for the 3B study).
Article
Obesity is a heritable disorder, with children of obese fathers at higher risk of developing obesity. Environmental factors epigenetically influence somatic tissues, but the contribution of these factors to the establishment of epigenetic patterns in human gametes is unknown. Here, we hypothesized that weight loss remodels the epigenetic signature of spermatozoa in human obesity. Comprehensive profiling of the epigenome of sperm from lean and obese men showed similar histone positioning, but small non-coding RNA expression and DNA methylation patterns were markedly different. In a separate cohort of morbidly obese men, surgery-induced weight loss was associated with a dramatic remodeling of sperm DNA methylation, notably at genetic locations implicated in the central control of appetite. Our data provide evidence that the epigenome of human spermatozoa dynamically changes under environmental pressure and offers insight into how obesity may propagate metabolic dysfunction to the next generation.
Article
PFOS is a chemical of nearly ubiquitous exposure in humans. Recent studies have associated PFOS exposure to adipose tissue-related effects. The present study was to determine whether PFOS alters the process of adipogenesis and regulates insulin-stimulated glucose uptake in mouse and human preadipocytes. In murine-derived 3T3-L1 preadipocytes, PFOS enhanced hormone-induced differentiation to adipocytes and adipogenic gene expression, increased insulin-stimulated glucose uptake at concentrations ranging from 10 to 100μM, and enhanced Glucose transporter type 4 and Insulin receptor substrate-1 expression. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2), NAD(P)H dehydrogenase, quinone 1 and Glutamate-cysteine ligase, catalytic subunit were significantly induced in 3T3-L1 cells treated with PFOS, along with a robust induction of Antioxidant Response Element (ARE) reporter in mouse embryonic fibroblasts isolated from ARE-hPAP transgenic mice by PFOS treatment. Chromatin immunoprecipitation assays further illustrated that PFOS increased Nrf2 binding to ARE sites in mouse Nqo1 promoter, suggesting that PFOS activated Nrf2 signaling in murine-derived preadipocytes. Additionally, PFOS administration in mice (100μg/kg/day) induced adipogenic gene expression and activated Nrf2 signaling in epididymal white adipose tissue. Moreover, the treatment on human visceral preadipocytes illustrated that PFOS (5 and 50μM) promoted adipogenesis and increased cellular lipid accumulation. It was observed that PFOS increased Nrf2 binding to ARE sites in association with Nrf2 signaling activation, induction of Peroxisome proliferator-activated receptor γ and CCAAT/enhancer-binding protein α expression, and increased adipogenesis. This study points to a potential role of PFOS in dysregulation of adipose tissue expandability, and warrants further investigations on the adverse effects of persistent pollutants on human health.
Article
Context: The Chinese were afflicted by great famine between 1959 and 1962. These people then experienced rapid economic development where the GDP per capita increased from $28 in 1978 to $6807 in 2013. We hypothesize that these two events are associated with the booming rate of diabetes in China. Objective: We aimed to explore whether exposure to famine in early life and high economic status in adulthood was associated with diabetes in later life. Design and setting: Our data of 6897 adults were from a cross-sectional SPECT-China study in 2014. Among them, 3844 adults experienced famine during different life stages, and then lived in areas with different economic statuses in adulthood. Main outcome measure: Diabetes was considered as fasting plasma glucose ≥7.0mmol/L, HbA1c ≥6.5% and/or a previous diagnosis by health care professionals. Results: Compared with non-exposed subjects, famine exposure during the fetal period (OR 1.53, 95% CI 1.09, 2.14) and childhood (OR 1.82, 95% CI 1.21, 2.73) was associated with diabetes after adjusting for age and gender. Further adjustments for adiposity, height, the lipid profile and blood pressure did not significantly attenuate this association. Subjects living in areas with high economic status had a greater diabetes risk in adulthood (OR 1.46, 95% CI, 1.20, 1.78). In gender-specific analyses, fetal-exposed men (OR 1.64, 95% CI, 1.04, 2.59) and childhood-exposed women (OR 2.81, 95% CI, 1.59, 4.97) had significantly greater risk of diabetes. Conclusions: The rapid increase in the prevalence of diabetes in middle-aged and elderly people in China is associated with the combination of exposure to famine during the fetal stage and childhood and high economic status in adulthood. Our findings may partly explain the booming diabetes phenomenon in China.
Article
Elevated blood or urinary concentrations of endocrine-disrupting chemicals (EDCs) may be related to increased type 2 diabetes (T2D) risk. The objective of this study was to assess the role of EDCs in affecting risk of T2D and related metabolic traits. Search of MEDLINE for cross-sectional and prospective studies published before March 8, 2014 for the association between EDCs [dioxin, polychlorinated biphenyl (PCB), chlorinated pesticide, bisphenol A (BPA), phthalates] and T2D and related metabolic traits. Three investigators independently extracted information on study design, participant characteristics, EDC types and concentrations, and association measures. We included 41 cross-sectional and 8 prospective studies from ethnically diverse populations. Serum concentrations of dioxins, PCBs, and chlorinated pesticides were significantly associated with T2D risk; comparing the highest to the lowest concentration category, the pooled relative risks were 1.91 (95% CI, 1.44 to 2.54) for dioxins, 2.39 (95% CI, 1.86 to 3.08) for total PCBs, and 2.30 (95% CI, 1.81 to 2.93) for chlorinated pesticides. Urinary concentrations of BPA and phthalates were also associated with T2D risk; comparing the highest to the lowest concentration categories, the pooled relative risks were 1.45 (95% CI, 1.13 to 1.87) for BPA and 1.48 (95% CI, 0.98 to 2.25) for phthalates. Further, EDC concentrations were associated with indicators of impaired fasting glucose and insulin resistance. Persistent and non-persistent EDCs may affect the risk of T2D. There is an urgent need for further investigation of EDCs, especially non-persistent ones, and T2D risk in large prospective studies. This article is protected by copyright. All rights reserved.
Article
There has been a substantial body of evidence, which has shown that genetic variation is an important determinant of disease risk. However, there is now increasing evidence that alterations in epigenetic processes also play a role in determining susceptibility to disease. Epigenetic processes, which include DNA methylation, histone modifications and non-coding RNAs play a central role in regulating gene expression, determining when and where a gene is expressed as well as the level of gene expression. The epigenome is highly sensitive to a variety of environmental factors, especially in early life. One factor that has been shown consistently to alter the epigenome is maternal diet. This review will focus on how maternal diet can modify the epigenome of the offspring, producing different phenotypes and altered disease susceptibilities.
Article
There is a global epidemic of obesity and diabetes, and current efforts to curb the diabetes epidemic have had limited success. Epidemiological studies have highlighted increased risk of obesity, diabetes and cardiovascular complications in offspring exposed to maternal diabetes, and gestational diabetes increases the risk of diabetes in subsequent generations, thereby setting up a vicious cycle of "diabetes begetting diabetes". This relationship between maternal hyperglycaemia and long-term health in the offspring is likely to become even more important with an increasing proportion of young woman being affected by diabetes, and the number of pregnancies complicated by hyperglycaemia continuing to rise. Animal models of gestational diabetes or maternal hyperglycaemia have highlighted long-term changes in the offspring with some instances of sex bias, including increased adiposity, insulin resistance, β-cell dysfunction, hypertension, as well as other structural and functional changes. Furthermore, several of these changes appear to be transmissible to later generations through the maternal line. Epigenetic changes play an important role in regulating gene expression, especially during early development. Recent studies have identified a number of epigenetic modifications in the offspring associated with maternal hyperglycaemia. In this review, we provide an overview of the epidemiological evidence linking maternal hyperglycaemia with adverse long-term outcome in the offspring, as well as of some of the studies that explore the underlying epigenetic mechanisms. A better understanding of the pathways involved may provide novel approaches for combating this global epidemic. Copyright © 2015. Published by Elsevier Ltd.
Article
Alcohol consumption throughout pregnancy can cause metabolic dysregulation, including glucose intolerance in progeny. This study determined if periconceptional (PC) alcohol (12% v/v in a liquid diet) (PC:EtOH) consumed exclusively around conception results in similar outcomes in Sprague-Dawley rats. Control (C) rats were given a liquid diet containing no alcohol but matched to ensure equal caloric intake. PC maternal alcohol intake (from 4 days before conception until day 4 of gestation), resulted in offspring with elevated fasting plasma glucose (∼10-25%, P < 0.05), impaired glucose tolerance (P < 0.05), and decreased insulin sensitivity (P < 0.01) at 6 months of age. This was associated with increased hepatic gluconeogenesis and sex-specific alterations in peripheral protein kinase B (AKT) signaling. These changes were accompanied by increased mRNA expression of DNA methyltransferases (DNMTs) 1, 3a, and 3b (1.5- to 1.9-fold, P < 0.05) in fetal liver in late gestation, suggesting PC:EtOH may cause epigenetic changes that predispose offspring to metabolic dysfunction. Exposure to a postnatal (PN) high-fat and cholesterol diet (HFD) from 3 months of age caused hyperinsulinemia (∼2-fold increase, P < 0.001) and exacerbated the metabolic dysfunction in male offspring exposed to PC:EtOH but had no additive effects in females. Given many women may drink alcohol while planning a pregnancy, it is crucial to increase public awareness regarding the effects of alcohol consumption around conception on offspring health.-Gårdebjer, E. M., Anderson, S. T., Pantaleon, M., Wlodek, M. E., Moritz, K. M. Maternal alcohol intake around the time of conception causes glucose intolerance and insulin insensitivity in rat offspring, which is exacerbated by a postnatal high-fat diet. © FASEB.
Article
Extensive experimental animal studies and epidemiological observations have shown that environmental influences during early development affect the risk of later pathophysiological processes associated with chronic, especially noncommunicable, disease (NCD). This field is recognized as the developmental origins of health and disease (DOHaD). We discuss the extent to which DOHaD represents the result of the physiological processes of developmental plasticity, which may have potential adverse consequences in terms of NCD risk later, or whether it is the manifestation of pathophysiological processes acting in early life but only becoming apparent as disease later. We argue that the evidence suggests the former, through the operation of conditioning processes induced across the normal range of developmental environments, and we summarize current knowledge of the physiological processes involved. The adaptive pathway to later risk accords with current concepts in evolutionary developmental biology, especially those concerning parental effects. Outside the normal range, effects on development can result in nonadaptive processes, and we review their underlying mechanisms and consequences. New concepts concerning the underlying epigenetic and other mechanisms involved in both disruptive and nondisruptive pathways to disease are reviewed, including the evidence for transgenerational passage of risk from both maternal and paternal lines. These concepts have wider implications for understanding the causes and possible prevention of NCDs such as type 2 diabetes and cardiovascular disease, for broader social policy and for the increasing attention paid in public health to the lifecourse approach to NCD prevention.
Article
Background The potential health risks of infant formula feeding are well established. This study investigated the opinions and perceptions of mothers and recommendations by hospital staff with respect to infant formula usage in China.MethodsA cross-sectional survey of 726 mothers within 6 months postpartum and 241 hospital staff, using structured questionnaires, was conducted in Hangzhou and Shenzhen, China.ResultsOverall, 474 of 726 (65.3%) infants aged within 6 months had consumed some infant formula. About 40.0 percent of mothers chose a hybrid brand of formula (manufactured in China but owned by a foreign company), over imported (< 32.0%) and domestic brands (< 28.0%), despite their higher level of confidence on the quality of imported brands. Perceived insufficient breastmilk production (86.2%) was the most common reason for giving infant formula, followed by return to work (24.6%). Of the 241 hospital staff, 97 (40.2%) gave no recommendation about infant formula brand for infants at any age. However, 47.2 percent of the remaining staff recommended a hybrid brand in combination with an imported and/or a domestic product.Conclusions Perceptions by mothers and recommendations from hospital staff appear to contribute to the widespread usage of infant formula in China. It is important to ensure breastmilk substitutes are prescribed to Chinese infants strictly for medical reasons. Maternal education programs incorporating information on food safety issues and establishment of breastfeeding-friendly workplaces could curtail the common practice of formula feeding in China.
Article
The prevalence of diabetes in China has increased substantially over recent decades, with more than 100 million people estimated to be affected by the disease presently. During this period there has been an increase in the rates of obesity and a reduction in physical activity. Many of the changes in lifestyle and diet are a result of increased economic development and urbanisation. In addition to an increasingly westernised diet, the traditional Chinese diet also plays a part, with the quantity and quality of rice intake linked to the risk of type 2 diabetes. Familial factors including inherited genetic variants are important, although differences in the genetic architecture suggest a different combination of genetic variants could be most relevant in Chinese when compared with Europeans. Recent advances have also emphasised the role of early life factors in the epidemic of diabetes and non-communicable diseases: maternal undernutrition, maternal obesity, and gestational diabetes are all linked to increased risk of diabetes in offspring. A mismatch between developmentally programmed biology and the modern environment is relevant for countries like China where there has been rapid economic transformation. Multisectoral efforts to address the risks will be needed at different stages throughout the lifecourse to reduce the burden of diabetes.
Article
China has a large burden of diabetes: in 2013, one in four people with diabetes worldwide were in China, where 11·6% of adults had diabetes and 50·1% had prediabetes. Many were undiagnosed, untreated, or uncontrolled. This epidemic is the result of rapid societal transition that has led to an obesogenic environment against a backdrop of traditional lifestyle and periods of famine, which together puts Chinese people at high risk of diabetes and multiple morbidities. Societal determinants including social disparity and psychosocial stress interact with factors such as low-grade infection, environmental pollution, care fragmentation, health illiteracy, suboptimal self-care, and insufficient community support to give rise to diverse subphenotypes and consequences, notably renal dysfunction and cancer. In the China National Plan for Non-Communicable Disease Prevention and Treatment (2012–15), the Chinese Government proposed use of public measures, multisectoral collaborations, and social mobilisation to create a health-enabling environment and to reform the health-care system. While awaiting results from these long-term strategies, we advocate the use of a targeted and proactive approach to identify people at high risk of diabetes for prevention, and of private–public–community partnerships that make integrated care more accessible and sustainable, focusing on registry, empowerment, and community support. The multifaceted nature of the societal and personal challenge of diabetes requires a multidimensional solution for prevention in order to reduce the growing disease burden.
Article
Background: The prevalence of diabetes is increasing in young adults in Asia, but little is known about metabolic control or the burden of associated complications in this population. We assessed the prevalence of young-onset versus late-onset type 2 diabetes, and associated risk factors and complication burdens, in the Joint Asia Diabetes Evaluation (JADE) cohort. Methods: JADE is an ongoing prospective cohort study. We enrolled adults with type 2 diabetes from 245 outpatient clinics in nine Asian countries or regions. We classified patients as having young-onset diabetes if they were diagnosed before the age of 40 years, and as having late-onset diabetes if they were diagnosed at 40 years or older. Data for participants' first JADE assessment was extracted for cross-sectional analysis. We compared clinical characteristics, metabolic risk factors, and the prevalence of complications between participants with young-onset diabetes and late-onset diabetes. Findings: Between Nov 1, 2007, and Dec 21, 2012, we enrolled 41,029 patients (15,341 from Hong Kong, 9107 from India, 7712 from Philippines, 5646 from China, 1751 from South Korea, 705 from Vietnam, 385 from Singapore, 275 from Thailand, 107 from Taiwan). 7481 patients (18%) had young-onset diabetes, with age at diagnosis of mean 32·9 years [SD 5·7] versus 53·9 years [9·0] with late-onset diabetes (n=33,548). Those with young-onset diabetes had longer disease duration (median 10 years [IQR 3-18]) than those with late-onset diabetes (5 years [2-11]). Fewer patients with young-onset diabetes achieved HbA1c concentrations lower than 7% compared to those with late-onset diabetes (27% vs 42%; p<0·0001) Patients with young-onset diabetes had higher mean concentrations of HbA1c (mean 8·32% [SD 2·03] vs 7·69% [1·82]; p<0·0001), LDL cholesterol (2·78 mmol/L [0·96] vs 2·74 [0·93]; p=0·009), and a higher prevalence of retinopathy (1363 [20%] vs 5714 (18%); p=0·011) than those with late-onset diabetes, but were less likely to receive statins (2347 [31%] vs 12,441 [37%]; p<0·0001) and renin-angiotensin-system inhibitors (1868 [25%] vs 9665 [29%]; p=0·006). Interpretation: In clinic-based settings across Asia, one in five adult patients had young-onset diabetes. Compared with patients with late-onset diabetes, metabolic control in those with young-onset diabetes was poor, and fewer received organ-protective drugs. Given the risk conferred by long-term suboptimum metabolic control, our findings suggest an impending epidemic of young-onset diabetic complications. Funding: The Asia Diabetes Foundation (ADF) and Merck.
Article
Objective: We evaluated the associations of both maternal and paternal smoking during pregnancy with the risk of type 2 diabetes in daughters and explored whether any association was explained by weight at birth or BMI throughout life. Research design and methods: We used data from 34,453 participants of the Nurses' Health Study II. We used Cox proportional hazards models to examine the associations of maternal and paternal smoking during pregnancy with incidence of type 2 diabetes in daughters between 1989 and 2009. Results: Maternal smoking during the first trimester only was associated with the risk of type 2 diabetes in the offspring, independent of confounders, birth weight, and later-life BMI (fully adjusted hazard ratio 1.34 [95% CI 1.01, 1.76]). In the age-adjusted models, both continued maternal smoking during pregnancy and paternal smoking tended to be associated with an increased risk of type 2 diabetes in daughters. Perinatal and adult life variables did not explain these associations, but additional adjustment for current BMI fully attenuated the effect estimates. Conclusions: The associations of maternal and paternal smoking during pregnancy with the risk of type 2 diabetes in daughters were largely explained by BMI throughout the life course. Further studies are needed to explore the role of first-trimester-only maternal smoking on insulin resistance in the offspring. Also, similar effect estimates for maternal and paternal smoking suggest that the associations reflect shared family-based or lifestyle-related factors.
Article
Background: Macrosomia, defined as a birthweight at least 4000 g, is a public health problem because of its adverse influences on maternal and neonatal outcomes. Studies show that there is an increasing prevalence of macrosomia births in developing countries. However, information on the epidemiology of macrosomia is limited in China. This study aimed to determine the prevalence and geographic variability of macrosomia in China and risk factors that can be targeted for intervention. Methods: A hospital-based, cross-sectional survey was conducted in 14 provinces in China, covering a wide range of geographic areas. The medical records of 101,723 singleton term infants born in 39 hospitals during 2011 were reviewed. Multiple logistic regression analysis was used to examine the associations between demographic characteristics and the risk of macrosomia. Results: The total prevalence of macrosomia was 7.3%. The prevalence varied between provinces, ranging from 4.1% to 13.4%. The prevalence of macrosomia in northern China (8.5%) was significantly higher than that in southern China (5.6%). Logistic regression analyses showed that risk of macrosomia was positively associated with maternal age, pre-pregnant body mass index (BMI), gravidity, parity, maternal height, gestational weight gain (GWG), gestational diabetes mellitus (GDM), and male fetal sex. Maternal BMI, gestational week, and GWG were the three risk factors most strongly associated with macrosomia. Conclusions: The prevalence of macrosomia varied dramatically between different areas of China. High pre-pregnancy BMI and GWG represent main modifiable risk factors for macrosomia and need more attention from health care providers.