The cilium 1 microscopic structure NSCT. The Cilium 2 intracellular trafficking NSCT

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 TRANSFERASETRIGLYCERIDE

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

10

20

30

40

50

60

70

80

90

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 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

Organ fibrosis in Alström syndrome

transplant

?prevention, TIPS, partial transplant

Transplant,Valve dysfunction

NSCT

DiabetesRenal dysfunctionHigh lipidshypertension

Carotid atheroma

PVD

Duplex-PVD

Coronary artery disease

NSCT

What diet? What Exercise?

Reduced carbohydrate Bespoke

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

NSCT