best predictive power for T1DM is the presence of “ antibodies to multiple pancreatic antigens at the same time... • suggests that some damage has been done to the pancreas by the time this antibody ‘cocktail’ is detected” ( Chervonsky 2012:311).
type 1 and type 2 diabetes • “Type 1 and type 2 diabetes have long been viewed as two diseases , the first auto-immune with a large genetic component , the second metabolic , linked to obesity and a sedentary lifestyle … • [research is now showing that] each type has more in common with the other than once believed: • both involve a faulty immune system and share some mechanisms that ultimately kill the insulin-producing beta cells in the pancreatic islets. • Yet in neither type 1 diabetes (T1D) nor type 2 diabetes (T2D) does genetics or behaviour fully explain why some people get the disease and others don’t… • scientists have implicated epigenetic and environmental influence in each type of diabetes.” ( Jonietz 2012:s10)
Pathogenesis of IDDM (type 1) • ~2/3 of beta-cells in the pancreas hare have been destroyed by an autoimmune response before the disease manifests itself (DeWeerdt 2012) • genetic disposition to the disease • “ runs in families…About 60% of the genetic risk comes from a few specific variants in the human leukocyte antigen (HLA) genes . .. • encode the proteins that present antigens to immune cells and are involved in the misguided immune response in T1D… • Normally, cytotoxic T cells destroy only infected cells • T cells that react to [self] …are eliminated before they mature…In type 1 diabetes… T cells primed to recognize beta cells enter circulation … • A number of factors appear to be involved, including variations in the gene encoding insulin, diet , and the presence or absence of certain bacteria in the gut flora “ ( Jonietz 2012:s10) • environmental event (monozygotic twins) initiates the process (e.g., viral infection )
Pathogenesis of NIDDM (type 2) • beta cell defects ( mass intact ) and insulin resistance in target cells • “The statistical connection between T2D and a high-calorie diet and sedentary lifestyle is well established…[causality not established]… • The data from genome-wide association studies (GWAS)…have identified more than 40 genes associated with T2D , most of them having to do with beta-cell function . • But…account for only about 10% of the apparent genetic causes . • Some genes implicated by GWAS are expressed only in adipocytes (fat cells )… Adipose tissue stores excess lipids , which are otherwise toxic to the body. • When fat cells malfunction and aren’t able to store away the extra lipids generated by overeating, lipids begin to accumulate in muscle tissue and in the liver…. aberrant build-up triggers insulin resistance[?] • Another consequence of abnormal adipose growth is inflammation… • Insulitis plays a role in type 2 diabetes [how?] ‘ ( Jonietz 2012:s11)
type 2 Diabetes: Thrifty Genotype • Socio-cultural changes – Nomadic
- Summer '19