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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