Genetics of Gestational Diabetes Mellitus

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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