note no cow’s milk or cow’s milk products (including but not limited to cheese and yoghurt)...
TRANSCRIPT
Note
No cow’s milk or cow’s milk products (including but not limited to cheese and yoghurt) under the age of one year
-casein (a protein in cow’s milk) is the putative issue with type 1 diabetes
Lecture 4a 28 January 2013 Diabetes
Type 1Type 2
Pathology-4aNutritional Intervention-4bFunctional Food/Nutraceutical Approaches-4c
Pathology Role of insulin
-produced in the beta cells of the pancreas
-initially synthesised as a single chain 86 amino acid polypeptide (pre-proinsulin)
-post-translational modification removes the amino terminal signal peptide
what is a signal peptide?
Role of insulin
-this give rise to proinsulin -insulin is created via the cleavage of an internal peptide (31mer) and the A (21mer) and B(30 mer) chains of insulin are then linked together by a disulphide linkage (enzyme responsible?)
Causes of Type 1-genetic-concordance is 30-70 % in identical twins
-polymorphisms in HLA complex appear to account for 40-50 % of Type 1
-HLA complex contains genes for the class II MHC molecules which present antigen to
helper T cells and are thus involved in initiating the immune response
-ability of class II MHC molecules to present antigen is dependent on the amino acid
composition of their antigen binding sites
Genetic
-amino acid substitutions may influence the specificity of the immune response by altering the binding affinity of
different antigens for the class II molecules
-10 % of genetic risk due to
polymorphisms in the promoter region of the insulin gene
Causes of Type 1-autoimmune- beta cells produced proteins that mediate draw lymphocytes into pancreas where they infiltrate islets (insulitis) and selectively attack beta cells- inflammation leads to atrophy of -cells -immunological markers-islet cell autoantibodies-these antibodies are directed at a series of -cell proteins -environmental-viruses-coxsackie and rubella
-bovine milk-nitrosamines
Causes of Type 2Key risk factors for type 2 diabetes:•Being 40 years of age or older•Genetics stronger factor than in type 1•Having a close relative (parent or sibling) who has type 2 diabetes-genetics•Being a member of a high-risk population, such as those of Aboriginal, Hispanic, Asian, South Asian or African descent-genetics•Having a history of impaired glucose tolerance or impaired fasting glucose•Having heart disease•Having a history of gestational diabetes-increased risk of type 2 diabetes in mum and offspring•Having high blood pressure•Having high cholesterol•Being overweight, especially around the abdomen-though overweight/obesity NOT THE WHOLE STORY
Type 2-no longer adult NIDDM - affects children and insulin can be used
-genetic factors
-concordance of 70-90 % in identical twins- question this
-40 % if both parents have it-question this as well
-polymorphisms or mutations in insulin receptor and enzymes involved in glucose homeostasis (candidates?)
-pathophysiology
-increased hepatic glucose synthesis because as insulin sensitivity drops the ability of
insulin to promote glycogen synthesis and suppress gluconeogenesis drops
-impaired insulin sensitivity
Pathophysiology continued
-impaired insulin production-reason is unknown-though glucose toxicity while undefined cripples beta cell-suggestions
-increased free fatty acids impair -cell function
Metabolic syndrome
-obesity-kick-off via increased free
fatty acids-measures
-BMI -percentage fat-skinfolds
underwater weighing
-height-weight tables
-free fatty acids regulate insulin sensitivity
Metabolic syndrome
-free fatty acids regulate insulin sensitivity
-free fatty acids decrease glucose utilisation and increase hepatic glucose production
-lipids-including decreased anti-oxidation capacity
-increased free fatty acids
-decreased HDLc, increased CETP, decreased LPL
-increased cholesterol, LDLc
-increased triglycerides
Metabolic syndrome
-blood pressure-elevated
-platelet aggregation- Trip- epidemiology slide
PLATELET HYPERREACTIVITY AND MYOCARDIAL INFARCTION*
SPA STATUS MORTALITY CARDIAC AND NUMBER EVENTSOF PATIENTS
TOTAL 149 18 33
SPA NEG. 94 6 (6.4 %) 14 (14.9 %)
SPA INT. 29 3 (10.3 %) 7 (24.1 %)
SPA POS. 26 9 (34.6 %) 12 (46.2 %)
12 MOS. DATA OF Trip et al. NEJM 322:1549 (1990)SPA = SPONTANEOUS PLATELET AGGREGATION
Metabolic syndrome
-insulin sensitivity-receptor binding efficiency
-right shift in insulin dose response curve and downward shift in maximal impact
-as insulin sensitivity goes down the lipids are further perturbed
-ultimately may get pancreatic failure with requirement for insulin injections