the cilium 1 microscopic structure nsct. the cilium 2 intracellular trafficking nsct
TRANSCRIPT
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The cilium 1 microscopic structure
NSCT
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The Cilium 2 intracellular trafficking
NSCT
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Glut 4 n
cochlea
photoreceptorGlucose transport
cochlea
Smooth muscle
cilium
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Organ fibrosis in Alström syndrome
NSCT
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Improvements with surgeryhttps://weightloss.clevelandclinic.org/images/Reduction3.gif
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INSULIN EFFECTS ON INTERMEDIARY METABOLISM
PLASMA PLASMAHEPATOCYTE
GLUCOSE
GLUTRECEPTOR
GLYCOGEN
GLUCOKINASE
PHOSPHORYLASE GLYCOGEN SYNTH
FRUCTOSE 6 PHOS GLYCOLYSIS
LACTATE
PYRUVATE
GLUCONEOGENESIS
CHOLESTEROL
MEVALONIC ACID
HMG CoA
PYRUVATE
ACETYL CoA
KETONEBODIES
TCACYCLE
REDUCTASE
MELONYL FATTY ACIDSCoA
CARNITINEACYL TRANSFERASETRIGLYCERIDE
OXIDATIVEPHOSPHORYLATION30ATP
INSULIN SENSITIVELIPOPROTEIN LIPASE
FA +GLYCEROL
TG
ADIPOCYTE
VLDL
MITOCHONDRION
INSULINSENSITIVE
రర
VLDL
LDL
HDL
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Exercise and insulin sensitivity
NSCT
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Effect of BMI on diabetes rate in Alström syndrome
BMI 28 BMI32 BMI360
10
20
30
40
50
60
70
80
90
100
column 2column 3
%
NSCT
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Within family diabetes trend progression
Jan 2011 Jan 2012
Weight Kg 69 74
HbA1c % 5.5 7.5
Trigsmmol/l 2.1 4.5
Blood pressure 120/75 142/90
ELF 8.1 9.4
remission
Jan 2011 Jan 2012
Weight Kg 76 70
HbA1c % 7.3 5.3
Trigsmmol/l 3.2 1.8
Blood Pressure 138/80 110/72
ELF 9.1 8.3
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new treatments in type2 diabetes
Incretins and glycaemic control7,8
Adapted from 7. Drucker DJ. Cell Metab. 2006;3:153–165. 8. Miller S, St Onge EL. Ann Pharmacother 2006;40:1336-1343.
Active GLP-1 and
GIP
Release of incretin gut hormones
Pancreas
Bloodglucose control
GI tract
Glucagon from alpha cells
(GLP-1)Glucose
dependent
Alpha cells
Increased insulin and decreasedglucagon reduce hepatic glucose output
Glucose dependent Insulin
from beta cells(GLP-1 and GIP)
Beta cells
Insulinincreases peripheral glucose uptake
Ingestion of food
DPP-4enzyme rapidly
degrades
incretins NSCT
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Alström Non DMN=18
Alström DMN=40
Type 2 DMN=30
P valueType2 vs
Alstrom DM
Age yrs 19.4 22 24.1 BMI Kg/m2 33.1 32.4(4.6 36.5(8 0.13Height m 160 160.2 165 0.07
Duration ofdiabetes
Na 8.7 4.6
HbA1c % 5.2 9.7 8.6 0.14Neuropathicsymptoms
0 0 30.1
% perception all 2g monofilament
80 95 36 0.001
%perceptionall10g monofilament
100 100 38 0.001
% perceived 128MHz vibration
100 97 72 0.001
neuropathy 0 0 34.6
Foot ulceration 0 0 16
Absence of neuropathy in Alström type 2 diabetes
NSCT
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Organ fibrosis in Alström syndrome
transplant
?prevention, TIPS, partial transplant
Transplant,Valve dysfunction
NSCT
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DiabetesRenal dysfunctionHigh lipidshypertension
Carotid atheroma
PVD
Duplex-PVD
Coronary artery disease
NSCT
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What diet? What Exercise?
Reduced carbohydrate Bespoke
• Weight training• Horse riding• Walking• Swimming• Cycling• Dancing
NSCT