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Mutations in HNF4α, which encodes hepatocyte nuclear factor-4α, can lead to adult-onset diabetes (MODY) in young adults
.
HNF4A-MODY is also related to congenital hyperinsulinemia (CHI) and neonatal hypoglycemia
Mutations in HNF4α, which encodes hepatocyte nuclear factor-4α, can lead to the onset of adult diabetes mellitus (MODY) in young adults
The level of fetal insulin secretion in humans is the main determinant of birth weight
We first tried to assess the impact of maternal diabetes history and HNF4A mutations on newborn weight
.
The birth weight of individuals with mutations was higher than that of family members without mutations (4.
The birth weight of individuals with mutations is higher than that of non-mutated family members.
Per kilogram of weight gain and diabetes diagnosis diagnostic rate has dropped 22% related
To assess whether birth weight is independently related to penetrance, we performed a multivariate COX proportional hazard survival analysis and adjusted for other factors that affect penetrance
.
To determine the factors associated with HNF4A-MODY penetrance, we compared the characteristics of diabetic and non-diabetic patients at age 20 (median age at diagnosis of diabetes in the cohort)
Every kilogram of body weight gains a 30% reduction in diabetes diagnosis
We found that in individuals with high-penetrability HNF4 mutations, higher birth weight is associated with decreased diabetes penetrance
.
We speculate that this reflects the correlation between individual fetal and adult insulin secretion capacity, that is , individuals with HNF4A mutations and higher birth weight have less decline in adult β-cell function
In individuals having a high permeability HNF4 mutations, dominant higher birth weight reduction of the outer diabetes less HNF4A carrying mutations and higher birth weight adult individuals decreased β-cell function
Mutations in the HNF4 gene are associated with an increase in birth weight that does not depend on glucose, while a higher birth weight is related to the relative protection of diabetes
.
(A) The sex and pregnancy-adjusted birth weight of individuals with HNF4 gene mutations (divided by whether they have diabetes during pregnancy) and the p-values of non-carrier relatives are calculated by Mann-WhitneyUtest
Mutations in the HNF4 gene are associated with an increase in birth weight that does not depend on glucose, while a higher birth weight is related to the relative protection of diabetes
Table 1 Cox proportional hazard survival regression analysis was used to determine the hazard ratio of HNF4a-MODY penetrance-related factors
Table 1 Cox proportional hazard survival regression analysis was used to determine the hazard ratio of HNF4a-MODY penetrance-related factorsIn short, this is one of the first and largest studies to study the factors affecting the penetrance of HNF4α-MODY, and it has determined the importance of birth weight as a potential prognostic and treatment-related indicator
.
.
Original source:
Locke JM, Dusatkova P, Colclough K, et al.
Locke JM, Dusatkova P, Colclough K, et al.
Association of birthweight and penetrance of diabetes in individuals with HNF4A-MODY: a cohort study.
Association of birthweight and penetrance of diabetes in individuals with HNF4A-MODY: a cohort study.
Diabetologia in This message