6- Diabetes Flashcards
Why is fat necessary?
vides insulation and supports and protects vital organs
It is a source of hormones, and is a regulator of reproduction. It is especially important in sexual
signalling
It also has a role in the immune system and aids wounds healing
Not having enough fat is a bad thing, and leads to infertility, miscarriage, and death from
infections etc.
How is obesity defined?
BMI of over 30 and morbid obesity is over 40
What is syndromic obesity?
There are around 30 known syndromic forms of obesity, i.e. those that are usually accompanied by mental retardation, and particular dysmorphic or clinical features
o Prader Willisyndromeisthemostcommon–imprintingdefect
What is monogenic obesity and give examples
affect appetite regulation
are dominant or recessive single gene disorders
Leptin – the first obese gene. This is a blood borne factor that controls appetite and stops people eating. The levels of this protein in the blood are an indicator of how much fat there is in the body.
body
Leptin causes a reduced food intake, reduced insulinaemia and reduced blood sugar
Other genes in the same pathway also cause single gene obesity
o PC1–recessiveobesity
o MC4R–mostcommonsingle geneformofobesity
What causes type 2 diabetes?
Resistance to insulin action → Increase in insulin production → Ultimately ‘pancreatic exhaustion’ and reduced secretion
What is Permanent neonatal diabetes?
Diabetes in first 6 months of life
What is MODY?
Collection of autosomal dominant monogenic disorders affecting genes involved in beta-cell glucose sensing and insulin secretion.
2-4% of all diabetes
What is common obesity and how do genes affect it?
Tested for with genome wide association studies (GWAS), which is hypothesis free, “common disease, common variant”
Looked at single nucleotide polymorphisms throughout the genome of people with common obesity and the GWAS identified SNPs only explain a small proportion of common obesity risk
It has only identified associations that are statistically strong and reliable, but the genetic component contribution is low, <5%
How does polygenic diabetes develop?
there has to be a second hit to develop diabetes
–environmental
–lifestyle
What is glucokinase MODY?
Mutations result in a higher set-point at which insulin secretion is triggered
Non-progressive mild life-long hyperglycaemia
•Not associated with long-term complications
•Seldom needs treatment
•Diagnosis means treatment can be stopped
What is HNF-1 alpha MODY?
Transcription factor normally stimulating insulin production
–Accounts for most MODY cases in the UK
•Usually best-managed with sulphonylureas
•Often stop insulin in patients who have been incorrectly diagnosed as T1DM
•At risk of future microvascular and macrovascular complications
•May eventually end up requiring insulin therapy
What is mitochondrial diabetes?
Maternally inherited
E.g.
Maternally inherited diabetes and deafness (MIDD) A3243G
•Myopathy, encephalopathy, lactic acidosis, stroke like episodes (MELAS)
