The cilium 1 microscopic structure

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The Cilium 2 intracellular trafficking

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Glut 4 n

cochlea

photoreceptorGlucose transport

cochlea

Smooth muscle

cilium

Organ fibrosis in Alström syndrome

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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

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Effect of BMI on diabetes rate in Alström syndrome

BMI 28 BMI32 BMI360

102030405060708090

100

column 2column 3

%

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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

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

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Organ fibrosis in Alström syndrome

transplant

?prevention, TIPS, partial transplant

Transplant,Valve dysfunction

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DiabetesRenal dysfunctionHigh lipidshypertension

Carotid atheroma

PVD

Duplex-PVDCoronary artery disease

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What diet? What Exercise?

Reduced carbohydrate Bespoke

• Weight training• Horse riding• Walking• Swimming• Cycling• Dancing

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