Objective： This review examines the evidence that： Diabetes is a state of DNA damage; pathophysiological factors in diabetes can cause DNA damage： DNA damage can cause mutations： and DNA mutation is ...linked to carcinogenesis. Data Sources： We retrieved information from the PubMed database up to January, 2014, using various search terms and their combinations including DNA damage, diabetes, cancer, high glucose, hyperglycemia, free fatty acids, palmitic acid, advanced glycation end products, mutation and carcinogenesis. Study Selection： We included data from peer-reviewed journals and a textbook printed in English on relationships between DNA damage and diabetes as well as pathophysiological factors in diabetes. Publications on relationships among DNA damage, mutagenesis, and carcinogenesis, were also reviewed. We organized this information into a conceptual framework to explain the possible causal relationship between DNA damage and carcinogenesis in diabetes. Results： There are a large amount of data supporting the view that DNA mutation is a typical feature in carcinogenesis. Patients with type 2 diabetes have increased production of reactive oxygen species, reduced levels of antioxidant capacity, and increased levels of DNA damage. The pathophysiological factors and metabolic milieu in diabetes can cause DNA damage such as DNA strand break and base modification （i.e., oxidation）. Emerging experimental data suggest that signal pathways （i.e., Akt/tuberin） link diabetes to DNA damage. This collective evidence indicates that diabetes is a pathophysiological state of oxidative stress and DNA damage which can lead to various types of mutation to cause aberration in cells and thereby increased cancer risk. Conclusions： This review highlights the interrelationships amongst diabetes, DNA damage, DNA mutation and carcinogenesis, which suggests that DNA damage can be a biological link between diabetes and cancer.
Psychosocial status and patient reported outcomes (PRO) depression and health-related quality-of-life (HRQoL) are major health determinants. We investigated the association between depression and ...clinical outcomes in Chinese patients with type 2 diabetes (T2D), adjusted for PRO.
Using prospective data from Hong Kong Diabetes Register (2013-2019), we estimated the hazard-ratio (HR, 95%CI) of depression (validated Patient Health Questionnaire 9 (PHQ-9) score≥7) with incident cardiovascular disease (CVD), ischemic heart disease (IHD), chronic kidney disease (CKD: eGFR<60 ml/min/1.73m
) and all-cause mortality in 4525 Chinese patients with T2D adjusted for patient characteristics, renal function, medications, self-care and HRQoL domains (mobility, self-care, usual activities, pain/discomfort, anxiety/depression measured by EQ-5D-3L) in linear-regression models.
In this cohort without prior events mean ± SD age:55.7 ± 10.6, 43.7% women, median (IQR) disease duration of 7.0 (2.0-13.0) years, HbA1c, 7.2% (6.6%-8.20%), 26.4% insulin-treated, 537(11.9%) patients had depressive symptoms and 1923 (42.5%) patients had some problems with HRQoL at baseline. After 5.6(IQR: 4.4-6.2) years, 141 patients (3.1%) died, 533(11.8%) developed CKD and 164(3.6%) developed CVD. In a fully-adjusted model (model 4) including self-care and HRQoL, the aHR of depression was 1.99 (95% confidence interval CI):1.25-3.18) for CVD, 2.29 (1.25-4.21) for IHD. Depression was associated with all-cause mortality in models 1-3 adjusted for demographics, clinical characteristics and self-care, but was attenuated after adjusting for HRQoL (model 4- 1.54; 95%CI: 0.91-2.60), though HR still indicated same direction with important magnitude. Patients who reported having regular exercise (3-4 times per week) had reduced aHR of CKD 0.61 (0.41-0.89). Item 4 of PHQ-9 (feeling tired, little energy) was independently associated with all-cause mortality with aHR of 1.66 (1.30-2.12).
Depression exhibits significant association with CVD, IHD, and all-cause mortality in patients with diabetes, adjusting for their HRQoL and health behaviors. Despite the association between depression and all-cause mortality attenuated after adjusting for HRQoL, the effect size remains substantial. The feeling of tiredness or having little energy, as assessed by item Q4 of the PHQ-9 questionnaire, was found to be significantly associated with an increased risk of all-cause mortality after covariate adjustments. Our findings emphasize the importance of incorporating psychiatric evaluations into holistic diabetes management.
ABSTRACT
Aims/Introduction
To determine the population health burden attributable to the development of diabetes among women with a history of gestational diabetes mellitus (GDM).
Materials and ...Methods
We conducted a retrospective analysis of women with a history of GDM attending the Hong Kong Hospital Authority between 2000 and 2019. The time‐varying population attributable fraction was calculated.
Results
A total of 76,181 women with a history of gestational diabetes mellitus were included, 6,606 of them developed diabetes during a median follow‐up of 8.6 years. The respective hazard ratios (95% confidence interval) among women with GDM who developed diabetes vs those with GDM only were 2.8 (2.2, 3.7) for cardiovascular disease (CVD), 4.8 (3.0, 7.7) for end‐stage kidney disease (ESKD), 2.2 (1.9, 2.6) for infection‐related hospitalization, and 1.8 (1.3, 2.4) for all‐cause mortality. The development of diabetes was associated with 1.3 (0.8, 1.7), 0.6 (0.3, 0.8), 3.2 (2.4, 4.0), and 0.5 (0.2, 0.9) additional incident cases per 1,000 person‐years, accounting for 24.0% (13.2%, 35.9%), 42.0% (22.5%, 58.8%), 10.8% (7.1%, 14.9%), and 6.0% (−3.1%, 16.1%) of absolute number of CVD, ESKD, infection‐related hospitalization, and all‐cause mortality over 20 years after GDM, respectively.
Conclusions
Diabetes is a significant contributor to the population health burden of some clinical outcomes in women with a history of gestational diabetes mellitus, but other risk factors need to be considered.
In this population‐based cohort of Chinese women with a history of gestational diabetes mellitus, we found that the subsequent development of diabetes in women with GDM increased the hazards of cardiovascular and kidney diseases by 3‐ to 5‐fold, infection‐related hospitalization and all‐cause mortality by 2‐fold, and cancer by 20%. By 20 years post‐GDM, diabetes accounted for close to one half of the new cases of end‐stage kidney disease and one quarter of cardiovascular disease. Our results indicate that diabetes is an important contributor to selected clinical events in women with a history of gestational diabetes mellitus although other risk factors need to be considered.
Familial hypercholesterolemia (FH) is an autosomal-dominant genetic disease characterized by elevated plasma levels of low-density lipoprotein cholesterol (LDL-C) and increased risk of premature ...atherosclerotic coronary heart disease (CHD). Patients with FH in Hong Kong were found by the identification of potential probands with primary hypercholesterolemia manifesting total cholesterol levels greater than 7.5 mmol/L or LDL-C levels greater than 4.9 mmol/L and undertaking cascade screening of available relatives in the Department of Medicine & Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong since the early 1990s. Our previous study in a group of 252 subjects from 87 pedigrees clinically diagnosed as having heterozygous FH reported the mean plasma LDL-C level as 7.2±1.5 mmol/L. Xanthomata were present in 40.6% of males and 54.8% of females. The prevalence of known CHD was relatively low at 9.9% in males and 8.5% in females. All FH patients were offered treatment with statins and many of them reached the LDL-C goal with a moderate or high dose of potent statin alone. Ezetimibe is usually added for patients who have not achieved target LDL-C levels on statin alone, particularly in patients with established CHD. Some FH patients who have not achieved the LDL-C targets with this combination have entered into clinical trials with new cholesterol-modifying agents such as the monoclonal antibodies to proprotein convertase subtilisin-kexin type 9. Increased awareness, early identification, and optimal treatment are essential to reduce the risk of CHD, increase life expectancy, and improve the quality of life of patients with FH.
Aims/Introduction
Women with gestational diabetes mellitus are at increased risk for type 2 diabetes. We characterized the association between maternal glycemia during pregnancy with long‐term ...outcomes.
Methods and Methods
In this prospective nested case–cohort study, participants were recalled for follow up with detailed evaluation including oral glucose tolerance test at 8, 15 and 22 years. Logistic regression was used to estimate the risk of developing impaired glucose tolerance/type 2 diabetes and metabolic syndrome at follow up. The association between maternal glycemia at pregnancy and follow up was evaluated by linear regression. We also charted trajectory of β‐cell function during follow up.
Results
The analysis included 121 women with a mean follow‐up period of 22.5 years, and a mean age of 50.3 years. Gestational diabetes was associated with an adjusted odds ratio of 2.48 (95% confidence interval 1.03–5.99) for combined diabetes/impaired glucose tolerance at follow up (P = 0.04). Women with a pre‐pregnancy body mass index ≥23 had an odds ratio of 5.43 (95% confidence interval 1.87–15.72) for metabolic syndrome at follow up, compared with those with body mass index <23 (P = 0.002). Both fasting and 2‐h glucose during pregnancy were strongly associated with glycemic indices at follow up (P‐value <0.001–0.016). Gestational diabetes was associated with impaired β‐cell function that remained relatively stable after the index pregnancy.
Conclusions
Chinese women with a history of gestational diabetes have a high prevalence of impaired glucose tolerance/type 2 diabetes at 22‐year follow up. Glucose levels during mid‐pregnancy are strongly associated with those of middle age.
In this long‐term follow‐up of women with GDM, we found that 2‐hour glucose during OGTT at pregnancy predicted β‐cell function (as measured by ODI) 22 years post‐partum. Results of 2‐hour glucose during OGTT at pregnancy is a more useful indicator of long‐term metabolic risk. Most of the cases which later converted to type 2 diabetes occurred within the first 15 years postpartum.
Aims/Introduction
β‐Cell dysfunction is a hallmark of type 2 diabetes. In a previous pilot study, we identified an association between genetic variants within the human DACH1 gene and young‐onset ...type 2 diabetes. Here, we characterized the function of dachb, the only dach homologue to be expressed in the pancreas, in developing zebrafish embryos.
Materials and Methods
We injected one‐cell stage embryos with a dachb‐morpholino (MO) or with the dachb‐MO and dachb messenger ribonucleic acid, and determined the effect on the development of the pancreatic islet. We also carried out quantitative polymerase chain reaction and ribonucleic acid sequencing on the dachb‐MO group to determine the effect of dachb knockdown on gene expression.
Results
MO‐mediated dachb knockdown resulted in impaired islet cell development, with a significant decrease in both the β‐cell and islet cell numbers. This islet developmental defect was rescued when embryos were co‐injected with dachb‐MO and dachb messenger ribonucleic acid. Knockdown of dachb was associated with a significant downregulation of the β‐cell specific marker gene, insa, and the somatostatin cell marker, sst2, as well as regulators of pancreas development, ptf1a, neuroD, pax6a and nkx6.1, and the cell cycle gene, insm1a. Furthermore, ribonucleic sequencing analysis showed an upregulation of genes enriched in the forkhead box O and mitogen‐activated protein kinase signaling pathways in the dachb‐MO group, when compared with the control groups.
Conclusions
Together, our results suggest the possible role of dachb in islet development in zebrafish.
Morpholino (MO)‐mediated knock‐down of dachb resulted in impaired islet cell development, with a significant decrease in both the β‐cell and islet cell numbers in zebrafish. Embryos co‐injected with dachb mRNA and dachb‐MO expressed a similar phenotype as the uninjected control groups, indicating rescue of the islet developmental defect. The studies highlight the role of dachb in islet development in zebrafish.
There is an epidemic of diabetes in Asia. Type 2 diabetes develops in East Asian patients at a lower mean body mass index (BMI) compared with those of European descent. At any given BMI, East Asians ...have a greater amount of body fat and a tendency to visceral adiposity. In Asian patients, diabetes develops at a younger age and is characterized by early β cell dysfunction in the setting of insulin resistance, with many requiring early insulin treatment. The increasing proportion of young‐onset and childhood type 2 diabetes is posing a particular threat, with these patients being at increased risk of developing diabetic complications. East Asian patients with type 2 diabetes have a higher risk of developing renal complications than Europeans and, with regard to cardiovascular complications, a predisposition for developing strokes. In addition to cardiovascular–renal disease, cancer is emerging as the other main cause of mortality. While more research is needed to explain these interethnic differences, urgent and concerted actions are needed to raise awareness, facilitate early diagnosis, and encourage preventive strategies to combat these growing disease burdens.
Associations between single nucleotide polymorphisms (SNPs) and aspirin resistance (AR) have been studied with variable results. The associations of genetic variants with AR may be helpful to explain ...why some individuals demonstrate aspirin insensitivity with this anti-platelet therapy. The purpose of this research was to investigate the effect of different genotypes in candidate genes on aspirin response in patients taking long-term aspirin therapy by measuring the serum thromboxane B2 (TXB2) and platelet function using the Multiplate® analyser.
A total of 266 patients with stable coronary heart disease (CHD) taking low-dose aspirin for long periods of time and without any other anti-platelet drugs medications were enrolled into the study. They were required to take 80 mg of aspirin every morning for a week including the day before blood tests. Blood samples were collected 24 h after the last dose. The 80 mg dose of aspirin was taken orally and blood samples were collected again 1 h later. The serum TXB2 levels were measured in samples at 24 h post-dose and 1 h post-dose using the EIA kit and platelet activity was determined using the Multiplate® Impedance Platelet Aggregometry (ASPI) assay. Genotyping assays were performed by the TaqMan SNP genotyping technique.
Of the 266 patients, only 251 patients were enrolled in the present study. The PTGS1/COX1-1676 A > G (rs1330344) and the PTGS2/COX2-765 G > C (rs20417) SNPs showed significant associations with the ASPI measurements in samples taken at 24 h post-dose, but not with the values at 1 h post-dose or with the TXB2 levels (P < 0.05).
Our results suggest that polymorphisms in the PTGS1/COX1 and the PTGS2/COX2 genes may be associated with reduced anti-aggregatory effects and increased the risk of AR, but future larger-scale cohort studies are necessary for further validation.
The last three decades have witnessed an epidemic rise in the number of people with 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 number may 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.
In 2016, meetings of groups of physicians and paediatricians with a special interest in lipid disorders and familial hypercholesterolaemia were held to discuss several domains of management of ...familial hypercholesterolaemia in adults and children in Hong Kong. After reviewing the evidence and guidelines for the diagnosis, screening, and management of familial hypercholesterolaemia, consensus was reached on the following aspects: clinical features, diagnostic criteria, screening in adults, screening in children, management in relation to target plasma low-density lipoprotein cholesterol levels, detection of atherosclerosis, lifestyle and behaviour modification, and pharmacotherapy.
PDF
