The Pancreas Study Question: Is the decrease in triglyceride - - PowerPoint PPT Presentation

The Pancreas Study –

Question: Is the decrease in triglyceride content of the pancreas specifically related to type 2 diabetes and it reversal? Or is it merely a generalised effect of loss of fat from the body? Design: Compare pancreas triglyceride in matched groups of people with and without type 2 diabetes undergoing identical weight loss

Baseline subject characteristics

Type 2 DM n=18 NGT N=9 Age (yr) 49.1 ± 1.6 46.3 ± 2.1 Weight (kg) 121.0 ± 3.0 114 ± 5.0 BMI (kg/m2) 42.7 ± 0.7 41.3 ± 1.0 DM duration (yr) 6.9 ± 0.5 HbA1c (%) 7.6±0.4 Insulin treated 3 SU treated 9

Steven et al, Diabetes Care 39(1):158-65; 2016

T2DM NGT

30 40 50 60

Fat mass (kg)

Fat mass in type 2 diabetic and normal glucose tolerance groups – before and after weight loss

Decrease body weight 13.60.7% 12.8  0.8%

T2DM NGT

5 10 15

Plasma glucose (mmol/l)

Fasting plasma glucose in T2DM and NGT – Before and after weight loss

p<0.001 Steven et al, Diabetes Care 39(1):158-65; 2016

Hepatic insulin resistance in T2DM and NGT – before and after weight loss

p<0.002 p<0.001 T2DM NGT

1 2 3 4

Hepatic insulin resistance (mmol.min-1.kgffm

• 1 pmol.l-1)

Steven et al, Diabetes Care 39(1):158-65; 2016

Liver fat in T2DM and NGT – before and after weight loss

T2DM NGT

5 10 15

Liver fat (%)

p<0.05 p<0.02 Steven et al, Diabetes Care 39(1):158-65; 2016

• 20

20 40 60 80 0.2 0.4 0.6 0.8 1.0 1.2 1.4

Time (min) ISR (nmol/min/m2)

• 20

20 40 60 80 0.2 0.4 0.6 0.8 1.0 1.2 1.4

Time (min) ISR (nmol/min/m2)

NGT

• 20

20 40 60 80 0.2 0.4 0.6 0.8 1.0 1.2 1.4

Time (min) ISR (nmol/min/m2)

• 20

20 40 60 80 0.2 0.4 0.6 0.8 1.0 1.2 1.4

Time (min) ISR (nmol/min/m2)

T2DM

Insulin secretion before and after weight loss

Baseline 8 weeks

T2DM NGT

0.0 0.1 0.2 0.3 0.4 0.5

First phase insulin response (nmol min-1 m-2)

First phase insulin secretion in T2DM and NGT – before and after weight loss

p<0.005 p<0.02 Steven et al, Diabetes Care 39(1):158-65; 2016

T2DM NGT

4 5 6 7 8

Pancreatic triacylglycerol (%)

Pancreatic triglyceride in T2DM and NGT – before weight loss and after weight loss

p<0.01 p<0.005

Pancreatic triglyceride (%)

Steven et al, Diabetes Care 39(1):158-65; 2016

T2DM NGT

4 5 6 7 8

Pancreatic triacylglycerol (%)

Pancreatic triglyceride in T2DM and NGT – before weight loss and after weight loss

p<0.005

Decrease of 1.2% Mean pancreas volume ~50ml

This represents ~0.6 grams of fat

Pancreatic triglyceride (%)

Steven et al, Diabetes Care 39(1):158-65; 2016

Conclusions

Weight loss over 8 weeks brings about loss of pancreatic triglyceride specifically in type 2 diabetes It is likely that type 2 diabetes is caused by less than 1 gram of fat in the pancreas