Assessment of pulsatile insulin secretion derived from peripheral plasma C-peptide concentrations by nonparametric stochastic deconvolution

Marcello C. Laurenti, Adrian Vella, Ron T. Varghese, James C. Andrews, Anu Sharma, Nana Esi Kittah, Robert A. Rizza, Aleksey V Matveyenko, Giuseppe De Nicolao, Claudio Cobelli, Chiara Dalla Man

Research output: Contribution to journalArticle

Abstract

The characteristics of pulsatile insulin secretion are important determinants of type 2 diabetes pathophysiology, but they are understudied due to the difficulties in measuring pulsatile insulin secretion noninvasively. Deconvolution of either peripheral C-peptide or insulin concentrations offers an appealing alternative to hepatic vein catheterization. However, to do so, there are a series of methodological challenges to overcome. C-peptide has a relatively long half-life and accumulates in the circulation. On the other hand, peripheral insulin concentrations reflect relatively fast clearance and hepatic extraction as it leaves the portal circulation to enter the systemic circulation. We propose a method based on nonparametric stochastic deconvolution of C-peptide concentrations, using individually determined C-peptide kinetics, to overcome these limitations. The use of C-peptide (instead of insulin) concentrations allows estimation of portal (and not post-hepatic) insulin pulses, whereas nonparametric stochastic deconvolution allows evaluation of pulsatile signals without any a priori assumptions of pulse shape and occurrence. The only assumption required is the degree of smoothness of the (unknown) secretion rate. We tested this method first on simulated data and then on 29 nondiabetic subjects studied during euglycemia and hyperglycemia and compared our estimates with the profiles obtained from hepatic vein insulin concentrations. This method produced satisfactory results both in the ability to fit the data and in providing reliable estimates of pulsatile secretion, in agreement with hepatic vein measurements. In conclusion, the proposed method enables reliable and noninvasive measurement of pulsatile insulin secretion. Future studies will be needed to validate this method in people with type 2 diabetes.

Original languageEnglish (US)
Pages (from-to)E687-E694
JournalAmerican journal of physiology. Endocrinology and metabolism
Volume316
Issue number5
DOIs
StatePublished - May 1 2019

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C-Peptide
Insulin
Hepatic Veins
Type 2 Diabetes Mellitus
Liver
Catheterization
Hyperglycemia
Half-Life
Pulse

Keywords

  • C-peptide kinetics
  • diabetes
  • hepatic extraction
  • insulin pulses

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

Cite this

Assessment of pulsatile insulin secretion derived from peripheral plasma C-peptide concentrations by nonparametric stochastic deconvolution. / Laurenti, Marcello C.; Vella, Adrian; Varghese, Ron T.; Andrews, James C.; Sharma, Anu; Kittah, Nana Esi; Rizza, Robert A.; Matveyenko, Aleksey V; De Nicolao, Giuseppe; Cobelli, Claudio; Dalla Man, Chiara.

In: American journal of physiology. Endocrinology and metabolism, Vol. 316, No. 5, 01.05.2019, p. E687-E694.

Research output: Contribution to journalArticle

Laurenti, Marcello C. ; Vella, Adrian ; Varghese, Ron T. ; Andrews, James C. ; Sharma, Anu ; Kittah, Nana Esi ; Rizza, Robert A. ; Matveyenko, Aleksey V ; De Nicolao, Giuseppe ; Cobelli, Claudio ; Dalla Man, Chiara. / Assessment of pulsatile insulin secretion derived from peripheral plasma C-peptide concentrations by nonparametric stochastic deconvolution. In: American journal of physiology. Endocrinology and metabolism. 2019 ; Vol. 316, No. 5. pp. E687-E694.
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AU - Andrews, James C.

AU - Sharma, Anu

AU - Kittah, Nana Esi

AU - Rizza, Robert A.

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AU - De Nicolao, Giuseppe

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AU - Dalla Man, Chiara

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AB - The characteristics of pulsatile insulin secretion are important determinants of type 2 diabetes pathophysiology, but they are understudied due to the difficulties in measuring pulsatile insulin secretion noninvasively. Deconvolution of either peripheral C-peptide or insulin concentrations offers an appealing alternative to hepatic vein catheterization. However, to do so, there are a series of methodological challenges to overcome. C-peptide has a relatively long half-life and accumulates in the circulation. On the other hand, peripheral insulin concentrations reflect relatively fast clearance and hepatic extraction as it leaves the portal circulation to enter the systemic circulation. We propose a method based on nonparametric stochastic deconvolution of C-peptide concentrations, using individually determined C-peptide kinetics, to overcome these limitations. The use of C-peptide (instead of insulin) concentrations allows estimation of portal (and not post-hepatic) insulin pulses, whereas nonparametric stochastic deconvolution allows evaluation of pulsatile signals without any a priori assumptions of pulse shape and occurrence. The only assumption required is the degree of smoothness of the (unknown) secretion rate. We tested this method first on simulated data and then on 29 nondiabetic subjects studied during euglycemia and hyperglycemia and compared our estimates with the profiles obtained from hepatic vein insulin concentrations. This method produced satisfactory results both in the ability to fit the data and in providing reliable estimates of pulsatile secretion, in agreement with hepatic vein measurements. In conclusion, the proposed method enables reliable and noninvasive measurement of pulsatile insulin secretion. Future studies will be needed to validate this method in people with type 2 diabetes.

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