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The cilium 1 microscopic structure. NSCT. The Cilium 2 intracellular trafficking. NSCT. photoreceptor. Glucose transport. Smooth muscle. cilium. cochlea. Organ fibrosis in Alström syndrome. NSCT. Improvements with surgery. https://weightloss.clevelandclinic.org/images/Reduction3.gif. - PowerPoint PPT Presentation
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The cilium 1 microscopic structure
NSCT
The Cilium 2 intracellular trafficking
NSCT
Glut 4 n
cochlea
photoreceptorGlucose transport
cochlea
Smooth muscle
cilium
Organ fibrosis in Alström syndrome
NSCT
Improvements with surgeryhttps://weightloss.clevelandclinic.org/images/Reduction3.gif
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 TRANSFERASE TRIGLYCERIDE
OXIDATIVEPHOSPHORYLATION30ATP
INSULIN SENSITIVELIPOPROTEIN LIPASE
FA +GLYCEROL
TG
ADIPOCYTE
VLDL
MITOCHONDRION
INSULINSENSITIVE
రర
VLDL
LDL
HDL
Exercise and insulin sensitivity
NSCT
Effect of BMI on diabetes rate in Alström syndrome
BMI 28 BMI32 BMI360
102030405060708090
100
column 2column 3
%
NSCT
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
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
Alström Non DMN=18
Alström DMN=40
Type 2 DMN=30
P valueType2 vs
Alstrom DMAge 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
Organ fibrosis in Alström syndrome
transplant
?prevention, TIPS, partial transplant
Transplant,Valve dysfunction
NSCT
DiabetesRenal dysfunctionHigh lipidshypertension
Carotid atheroma
PVD
Duplex-PVDCoronary artery disease
NSCT
What diet? What Exercise?
Reduced carbohydrate Bespoke
• Weight training• Horse riding• Walking• Swimming• Cycling• Dancing
NSCT
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