1. Endocrine Society Annual Meeting
Impaired Glucose Tolerance Is Associated with Impaired Rise in Basal Insulin Secretion during Sustained Hyperglycemia
Endocrine Society Annual Meeting
Ron T. Varghese, MBBS1, Nana Esi Nkuma Kittah, MB.ChB1, James C. Andrews, MD1, Chiara Dalla Man, PhD2, Robert A Rizza1, Claudio Cobelli, PhD2, Aleksey Matveyenko1 and Adrian Vella, MD1.
1Mayo Clinic, Rochester, MN, USA, 2University of Padova, Padova, Italy

2. What is prediabetes ? Transitory state to Diabetes
86 million people (1 in 3 adults) in USA
Higher risk of developing diabetes
Higher risk for developing macrovascular complications
Edelstein SL et al. Diabetes 46: , Meigs et al. Diabetes Care. 2002;25:1845–1850
Ford et al. J Am Coll Cardiol 55: , DECODE. Arch Intern Med. 2001;161:397–405

3. Potential Role of Insulin Pulsatility
Partial pancreatectomy (50 %) in dogs caused a approximately 40% decrease in insulin-stimulated glucose disposal
Physiological insulin pulses delivered into the portal vein enhance insulin action in dogs.
Does insulin pulsatility change in prediabetes?
Matveyenko et al. Diabetes Aug;55(8):
Matveyenko et al. Diabetes 2012 Sep; 61(9):

4. Specific Aim
To determine if insulin pulse amplitude and frequency differ in humans with Impaired Glucose Tolerance (IGT) or Normal Glucose Tolerance (NGT).

5. Hypothesis
1º Hypothesis: Insulin pulse amplitude is decreased in people with IGT compared to those with NGT
2º Hypothesis: Insulin pulse interval is increased in people with IGT compared to those with NGT

6. Study Design - Recruitment
Mayo Clinic Biobank
n = ~ 50,000
Genotyping of a random sample at rs CC TT
NGT
IGT

7. Study Design – Hepatic Vein Sampling
Glucose Infusion*
*Glucose infusion (to maintain glucose at ~ 8.3 mmol/l)
Placement of hepatic vein catheter
Sampling Interval 1
Sampling Interval 2
Indocyanine Green

8. Demographic Characteristics

9. Pulse Measurements

10. Pulse Characteristics

11. Glucose concentrations
Fasting
Hyperglycemia

12. Pulse amplitude

13. Pulse interval

14. Pulse mass

15. Pulsatile secretion

16. Non – Pulsatile secretion

17. Total secretion

18. Response to Hyperglycemia (sym % change)

19. Summary
Insulin pulse amplitude and interval do not differ in IGT and NGT.
Insulin pulse mass does not differ between the two groups.
IGT is associated with impaired basal insulin secretion in response to hyperglycemia.
Net insulin secretion is unchanged because of a compensatory increase in mean pulse mass.

20. Conclusions
Insulin pulse interval or amplitude is not altered by glucose tolerance status in non-diabetic subjects.
The net contribution of basal (non-pulsatile) secretion to total insulin secretion in response to hyperglycemia is impaired in these subjects with IGT.

21. Acknowledgements Research Volunteers CTSA/CRU staff Mayo Clinic
Dr. Adrian Vella
Dr. Robert Rizza
Dr. Michael Jensen
Dr. James Andrews
Dr. Aleksey Matveyenko
Dr. Meera Shah
Dr. Anu Sharma
Dr. Nana Esi Kittah
Paula Giesler
Jeanette Laugen
Gail DeFoster
CTSA/CRU staff
University of Padova, Italy
Dr. Claudio Cobelli
Dr. Chiara Dallaman
Marcello Laurenti
Funding - NIH
Dr. Vella – DK
Training Grant —
2 T32 DK