DIABETES Flashcards
cutoff points for diabetes
Fasting PG: >7.0mmol/L
2 h PG >11.1mmol/L
A1c >6.5%
what are teh 5 types of diabetes
• Type 1 (beta cell destruction)- 1 A – autoimmune 1 B – idiopathic • Type 2 (insulin resistance/insulin secretory defect) • Secondary diabetes (specified) • Other genetic syndromes • Gestational diabetes
What are the risk factors for T1 DM?
Autoimmune beta cell destruction of the pancreas
RISK FACTORS
include genetic susceptibility;
immune factors (other autoimmune diseases) & antigen specific antibodies;
environmental triggers - viruses (enteroviruses, coxsackie, congenital rubella; food (eg. Early exposure to cows milk, proteins, cereals, gluten);
vitamin D deficiency; nitrosamines (cured meat); chemicals; microbiome; ?birthweight/pancreatic size
what are some features of the pancreas in Type 1A DM?
in Type 1A diabetes.
- Insulinitis of islet cells (mixed mononuclear infiltrate)
- loss of beta cells
- hypoexpression of class 1MHC
- Beta cell necrosis and apoptosis
Pancreas atrophy in dorsal region
glucagon staining islets in type 1A
Waht is the pathogenesis of T1DM?
T cell mediated autoimmune whereby the insulin producing beta cells of the pancreas are destroyed.
Hyperglycemia accomponied by classic symptoms will only occur when 70-90% of the pancreas has been destroyed.
What is insulinitis?
Insulinitis: infiltration of the islets with mononuclear cells containing activated macrophages, helper cytotoxic and suppressor T lymphocytes, natural killer cells and B lymphocytes.
What is a “fertile field”?
A fertile field occurs after exposure to one or more environmental triggers in susceptible individuals.
leads to aberrant
T-cell activation, insulitis,
beta cell destruction and a humoral (B cell) response with the production of antibodies to beta cell antigens – insulin, glutamic acid decarboxylase (GAD), insulinoma-associated protein 2 (IA-2) and tyrosine phosphatase or zinc transporter (ZnT8)
What are the genetics of Type 1A DM?
HLA (human leucocyte antigen ) region within the major histocompatibility complex of chromosome6pm21 ;
this locus is designated as IDDM1.
Susceptibility genes encode antigen presenting molecules. With the highest risk HLA halotypes DRB10401-DQB10302 and DRB10301-DQB10201. 1:20 children with both halotypes develop type 1 diabetes by the age of 15. (55% risk if sibling has diabetes and same halotypes). Non-HLA loci (INS, CTLA4, PTPN22 etc) exert effects on antigen driven T cell activation and cytokine signaling, proliferation and maturation and exert modest individual effects on risk (OR <1.3)
What is diabetes accelerated by?
Diabetes is accelerated by germ free conditions and a modified diet.
Research has suggested that there is a unified basis to this disease
environment & genes -> activation of inflammatory pathways ->
1) promotion of insulin resistance - T2DM
2) Promotion of adaptive immunity (T1DM)
Management for T1DM?
o Early, aggressive intervention to normalize BGL’s
o Intensive insulin therapy (MDII/CSII – “insulin pump”)
Pathogenesis of T2DM?
Insulin resistance -> pancreatic inflammation?
Risk factors for Type 2 DM are also CVD risk factors and together are grouped as “metabolic syndrome”
impaired glucose tolerance (insulin resistance), central obesity, HTN, and dyslipidemia
How does weight influence T2DM?
The primary cause of insulin resistance remains unclear.
Intra-abdominal ‘central’ adipose tissue is metabolically active, and releases large quantities of FFAs which may induce insulin resistance because they compete with glucose as a fuel for oxidation in peripheral tissues such as muscle.
In addition, adipose tissue releases a number of hormones(including adipokines) which act on specific receptors to influence sensitivity to insulin in other tissues. Because visceral adipose tissue drains into the portal vein, central obesity may have a particularly potent influence on insulin sensitivity in the liver, and thereby adversely affect gluconeogenesis and hepatic lipid metabolism.
With increasing weight gain, you get bodily changes->
Adipocytokines release: Adiponectin, Leptin , Resistin
Macrophage derived factors: Resistin, Il-1beta
Proinflammatory cytokines and chemokines release: TNF, IL-6, CCL2
All of which lead to atherogenesis; hepatic steatosis; insulin resistance + beta cell dysfunction = diabetes
