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Genetics of GDM
Dr. Mashfiqul HasanPhase B Resident
Department of Endocrinology BSMMU
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Overview of presentation
• What is GDM• Pathogenesis of GDM• Importance of GDM• Genetics of GDM• Scope of Genetic study in BSMMU• Principles of genetic study
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1. WHAT IS GDM?
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Definition
• Any degree of glucose intolerance with onset or first recognition during pregnancy
• Whether or not the condition persisted after pregnancy
• Not excluding the possibility that unrecognized glucose intolerance may have antedated or begun concomitantly with the pregnancy
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Limitations ?
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To overcome the limitation
• Screen women with risk factors for type 2 diabetes for diabetes at their initial prenatal visit, using standard diagnostic criteria
• Women with diabetes found at this visit should receive a diagnosis of overt, not gestational, diabetes
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Diagnostic criteria
• Still much controversies• ADA 2013• When any of the following plasma glucose
values are exceeded –– Fasting ≥ 5.1 mmol/L– 1h ≥ 10.0 mmol/L– 2h ≥ 8.5 mmol/L
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2. PATHOGENESIS OF GDM
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Hormone & fuel balance in pregnancy
• Early pregnancy
– Prepare the mother
– Accentuation of fat deposition
– Expansion of β cell mass
– α cells remain unchanged
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Hormone & fuel balance in pregnancy
• As the pregnancy progresses
– Increasing insulin resistance (50%)
– Increased insulin production from the previously
expanded cells (threefold)
– Increased lipolysis in adipose tissue leads to a shift
toward fatty acid utilization by maternal tissues
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Hormone & fuel balance in pregnancy
• Increased insulin resistance
– Facilitated Anabolism
• Increased lipolysis in mother
– Accelerated starvation
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It is said that a large proportion of GDM women are experiencing
Future T2DM in advance
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3. IMPORTANCE OF GDM
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Prevalence
• Reflects prevalence of type 2 DM in population
• GDM affects 3% to 15% of pregnancies • In Bangladesh, a pilot study done in a tertiary
care hospital showed that the prevalence of GDM was 7.8%
• >30% in GDM study, BSMMU
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Complications of GDM
• Fetal risk
• Maternal risk
• Future risk of DM
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4. GENETICS OF GDM
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Heritability of GDM
• Positive family history (45.1% in GDM study, BSMMU)
• Both GDM women and their offspring are at increased risk of future development of T2DM
• It can be hypothesized that GDM and type 2 diabetes share a common genetic background
• It is not known whether there are genetic risk loci specific to GDM
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Genetic factors in T2DM
• Differences between ethnic groups• Concordance in Monozygotic twins • Clustering in family
• Polygenic inheritence
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Approaches for genetic study
1. Candidate gene study
2. Genome wide association study
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5. SCOPE OF GENETIC STUDIES
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Scope of GDM study, BSMMU
• To investigate whether the candidate genes
that confer susceptibility to T2DM are also
correlated with GDM in pregnant Bangladeshi
women.
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6. PRINCIPLES OF GENETIC STUDY
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Building blocks of DNA
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Acknowledgement
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Thank You