scholarly journals Identification of HNF4A Mutation p.T130I and HNF1A Mutations p.I27L and p.S487N in a Han Chinese Family with Early-Onset Maternally Inherited Type 2 Diabetes

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Ying Yang ◽  
Tai-Cheng Zhou ◽  
Yong-Ying Liu ◽  
Xiao Li ◽  
Wen-Xue Wang ◽  
...  

Maturity-onset diabetes of the young (MODY) is characterized by the onset of diabetes before the age of 25 years, positive family history, high genetic predisposition, monogenic mutations, and an autosomal dominant mode of inheritance. Here, we aimed to investigate the mutations and to characterize the phenotypes of a Han Chinese family with early-onset maternally inherited type 2 diabetes. Detailed clinical assessments and genetic screening for mutations in theHNF4α,GCK,HNF-1α,IPF-1,HNF1β, andNEUROD1genes were carried out in this family. One HNF4A mutation (p.T130I) and two HNF1A polymorphisms (p.I27L and p.S487N) were identified. Mutation p.T130I was associated with both early-onset and late-onset diabetes and caused downregulatedHNF4Aexpression, whereas HNF1A polymorphisms p.I27L and p.S487N were associated with the age of diagnosis of diabetes. We demonstrated that mutation p.T130I in HNF4A was pathogenic as were the predicted polymorphisms p.I27L and p.S487N in HNF1A by genetic and functional analysis. Our results show that mutations inHNF4AandHNF1Agenes might account for this early-onset inherited type 2 diabetes.

2021 ◽  
pp. 1-11
Author(s):  
Baizid Khoorshid Riaz ◽  
Shahjada Selim ◽  
Megan Neo ◽  
Md Nazmul Karim ◽  
M. Mostafa Zaman

<b><i>Methodology:</i></b> Biochemically confirmed type 2 diabetes mellitus (T2DM) patients (<i>n</i> = 1,114) were recruited from the outpatient department of 2 tertiary care hospitals in Dhaka, Bangladesh. Face-to-face interview was conducted using a semi-structured questionnaire containing sociodemographic parameters and relevant information about depression and diabetes. Biochemical test results and treatment-related information were taken from patients’ records. The Hospital Anxiety and Depression Scale (HADS) was used to screen all patients for psychiatric manifestation. Those diagnosed by HADS were subsequently reassessed using structured clinical interview for DSM-5 Disorders – Clinician Version. T2DM diagnosed at age &#x3c;40 years were considered as early onset T2DM. Association between age of onset category and depression was assessed using multivariable mixed-effect logistic regression adjusting for random variation of the area of residence and plausible confounders. <b><i>Results:</i></b> Around a third of the participants (32.5%) were diagnosed with T2DM before the age of 40 years. Early onset T2DM patients were found to have 57% increase in the risk of developing depression (OR 1.57; 95% CI 1.13–2.28; <i>p</i> = 0.011) in comparison to those with usual onset T2DM (≥40 years). Among other factors a positive family history for diabetes (OR 1.33; 95% CI 1.03–1.78; <i>p</i> = 0.038), poor glycemic control (OR 1.31; 95% CI 1.03–1.68; <i>p</i> = 0.028), presence of 1, or more diabetic complications (OR 1.37; 95% CI 1.03–1.78; <i>p</i> = 0.011) also showed increased risk of depression. <b><i>Conclusion:</i></b> Early onset T2DM patients are at greater risk of developing depression. The finding is likely to help in setting preventive strategies aiming to reduce the presence of concomitant depression symptoms among diabetes.


2015 ◽  
Vol 7 (6) ◽  
pp. 858-863 ◽  
Author(s):  
Manna Zhang ◽  
Jiao Jiao Zhou ◽  
Wenjie Cui ◽  
Yan Li ◽  
Peng Yang ◽  
...  

Author(s):  
K. Wang ◽  
H. Liu

BACKGROUND: This study aimed to assess the relation of early-onset type 2 diabetes (age<55years) versus later in life to the risk of dementia, Alzheimer Disease (AD) dementia and stroke. Methods: This study was based on the Framingham Heart Study Offspring cohort (FHS-OS) which is a community-based prospective cohort. Glycemic status was ascertained at serial examinations over six decades among participants who initially did not have diabetes. Surveillance for incident events including dementia and stroke has been continued for approximately 30 years. Results: At baseline, there were 142 (5%) subjects with onset of diabetes prior to age 55 years, 172 (6%) subjects with 55-64 years, 349 (11%) subjects over 65 years and 2389 (78%) subjects without diabetes. The risk of dementia, AD and stroke increased with decreasing age of diabetes onset (P<0.05, for trend). Compared with never developing diabetes, early-onset diabetes conferred a higher risk of all dementia, AD dementia and stroke [HR 2.86(1.16-5.51) for dementia; HR 2.42(1.63-4.33) for AD; HR 2.85(1.37-3.98) for stroke]. Whereas later-onset diabetes was only associated with greater risk for stroke, neither dementia nor AD. Conclusion: Early-onset diabetes was stronger associated with an increased risk of all dementia, AD dementia and stroke than later-onset.


2009 ◽  
Vol 70 (6) ◽  
pp. 847-853 ◽  
Author(s):  
Nattachet Plengvidhya ◽  
Watip Boonyasrisawat ◽  
Nalinee Chongjaroen ◽  
Prapaporn Jungtrakoon ◽  
Sutin Sriussadaporn ◽  
...  

JAMA Surgery ◽  
2016 ◽  
Vol 151 (9) ◽  
pp. 798 ◽  
Author(s):  
Lwin Aung ◽  
Wei-Jei Lee ◽  
Shu Chun Chen ◽  
Kong-Han Ser ◽  
Chun-Chi Wu ◽  
...  

Author(s):  
Jian-Jun Liu ◽  
Sylvia Liu ◽  
Jiexun Wang ◽  
Janus Lee ◽  
Justin I-Shing Tang ◽  
...  

Abstract Context Early-onset diabetes has been associated with unfavorable cardiovascular risk but data on heart failure (HF) in this subpopulation are scarce. Objective We aimed to study the risk of, and risk factors for, incident HF in individuals with early-onset type 2 diabetes. Methods We studied 606 individuals with type 2 diabetes diagnosed before 40 years of age (early-onset) and 1258 counterparts with diabetes diagnosed from 41 to 65 years of age (usual-onset) with no HF history, at a regional hospital, over a median follow-up period of 7.1 years. Incident HF by European Cardiology Society criteria was determined. Results A total of 62 and 108 HF events were identified in the early- and usual-onset groups (1.55 and 1.29 per 100 patient-years), respectively. Compared with usual-onset counterparts, individuals with early-onset diabetes had a 1.20-fold unadjusted (95% CI, 0.88-1.63; P = 0.26) and 1.91-fold age-adjusted (95% CI, 1.37-2.66; P &lt; 0.001) hazard ratio (HR) for incident HF. Adjustment for traditional cardiometabolic risk factors only moderately mitigated the hazards (adjusted HR 1.69; 95% CI, 1.19-2.40; P = 0.003). However, additional adjustment for estimated glomerular filtration rate and albuminuria markedly attenuated the association of early-onset age with incident HF (adjusted HR 1.24; 95% CI, 0.87-1.77; P = 0.24). Notably, a long diabetes duration was not significantly associated with HF risk after accounting for kidney measures. Conclusion Individuals with early-onset diabetes have at least the same absolute risk and a 2-fold age-adjusted relative risk for incident HF. Excess cardiorenal risk factors but not a long diabetes duration are main drivers for HF development in this diabetic population.


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