Glucose excursions between states of glycemia with progression to type 1 diabetes in the Diabetes Prevention Trial-Type 1 (DPT-1)

Jay M Sosenko, Jay S Skyler, Jeffrey P. Krischer, Carla J. Greenbaum, Jeffrey Mahon, Lisa Rafkin, David Cuthbertson, Catherine Cowie, Kevan Herold, George Eisenbarth, Jerry P. Palmer

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

OBJECTIVE - We characterized fluctuations between states of glycemia in progressors to type 1 diabetes and studied whether those fluctuations are related to the early C-peptide response to oral glucose. RESEARCH DESIGN AND METHODS - Oral glucose tolerance tests (OGTTs) from differing states of glycemia were compared within individuals for glucose and C-peptide. Dysglycemic OGTTs (DYSOGTTs) were compared with normal OGTTs (NLOGTT), while transient diabetic OGTTs (TDOGTTs) were compared with subsequent nondiabetic OGTTs and with OGTTs performed at diagnosis. RESULTS - Of 135 progressors with four or more OGTTs, 30 (22%) went from NLOGTTs to DYSOGTTs at least twice. Area under the curve (AUC) glucose values from the second NLOGTT were higher (P < 0.001) than values from the first NLOGTT. Among 98 progressors whose DYSOGTTs and NLOGTTs were synchronized for the time before diagnosis, despite higher glucose levels (P < 0.01 at all time points) in the DYSOGTTs, 30-to 0-min C-peptide difference values changed little. Likewise, 30-to 0-min C-peptide difference values did not differ between TDOGTTs and subsequent (within 3 months) nondiabetic OGTTs in 55 progressors. In contrast, as glucose levels increased overall from the first to last OGTTs before diagnosis (P < 0.001 at every time point, n = 207), 30- to 0-min C-peptide difference values decreased (P < 0.001). CONCLUSIONS - Glucose levels fluctuate widely as they gradually increase overall with progression to type 1 diabetes. As glucose levels increase, the early C-peptide response declines. In contrast, glucose fluctuations are not related to the early Cpeptide response. This suggests that changes in insulin sensitivity underlie the glucose fluctuations.

Original languageEnglish
Pages (from-to)2386-2389
Number of pages4
JournalDiabetes
Volume59
Issue number10
DOIs
StatePublished - Oct 1 2010

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Glucose Tolerance Test
Type 1 Diabetes Mellitus
Glucose
C-Peptide
Reference Values
Area Under Curve
Insulin Resistance
Research Design

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Glucose excursions between states of glycemia with progression to type 1 diabetes in the Diabetes Prevention Trial-Type 1 (DPT-1). / Sosenko, Jay M; Skyler, Jay S; Krischer, Jeffrey P.; Greenbaum, Carla J.; Mahon, Jeffrey; Rafkin, Lisa; Cuthbertson, David; Cowie, Catherine; Herold, Kevan; Eisenbarth, George; Palmer, Jerry P.

In: Diabetes, Vol. 59, No. 10, 01.10.2010, p. 2386-2389.

Research output: Contribution to journalArticle

Sosenko, JM, Skyler, JS, Krischer, JP, Greenbaum, CJ, Mahon, J, Rafkin, L, Cuthbertson, D, Cowie, C, Herold, K, Eisenbarth, G & Palmer, JP 2010, 'Glucose excursions between states of glycemia with progression to type 1 diabetes in the Diabetes Prevention Trial-Type 1 (DPT-1)', Diabetes, vol. 59, no. 10, pp. 2386-2389. https://doi.org/10.2337/db10-0534
Sosenko, Jay M ; Skyler, Jay S ; Krischer, Jeffrey P. ; Greenbaum, Carla J. ; Mahon, Jeffrey ; Rafkin, Lisa ; Cuthbertson, David ; Cowie, Catherine ; Herold, Kevan ; Eisenbarth, George ; Palmer, Jerry P. / Glucose excursions between states of glycemia with progression to type 1 diabetes in the Diabetes Prevention Trial-Type 1 (DPT-1). In: Diabetes. 2010 ; Vol. 59, No. 10. pp. 2386-2389.
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abstract = "OBJECTIVE - We characterized fluctuations between states of glycemia in progressors to type 1 diabetes and studied whether those fluctuations are related to the early C-peptide response to oral glucose. RESEARCH DESIGN AND METHODS - Oral glucose tolerance tests (OGTTs) from differing states of glycemia were compared within individuals for glucose and C-peptide. Dysglycemic OGTTs (DYSOGTTs) were compared with normal OGTTs (NLOGTT), while transient diabetic OGTTs (TDOGTTs) were compared with subsequent nondiabetic OGTTs and with OGTTs performed at diagnosis. RESULTS - Of 135 progressors with four or more OGTTs, 30 (22{\%}) went from NLOGTTs to DYSOGTTs at least twice. Area under the curve (AUC) glucose values from the second NLOGTT were higher (P < 0.001) than values from the first NLOGTT. Among 98 progressors whose DYSOGTTs and NLOGTTs were synchronized for the time before diagnosis, despite higher glucose levels (P < 0.01 at all time points) in the DYSOGTTs, 30-to 0-min C-peptide difference values changed little. Likewise, 30-to 0-min C-peptide difference values did not differ between TDOGTTs and subsequent (within 3 months) nondiabetic OGTTs in 55 progressors. In contrast, as glucose levels increased overall from the first to last OGTTs before diagnosis (P < 0.001 at every time point, n = 207), 30- to 0-min C-peptide difference values decreased (P < 0.001). CONCLUSIONS - Glucose levels fluctuate widely as they gradually increase overall with progression to type 1 diabetes. As glucose levels increase, the early C-peptide response declines. In contrast, glucose fluctuations are not related to the early Cpeptide response. This suggests that changes in insulin sensitivity underlie the glucose fluctuations.",
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T1 - Glucose excursions between states of glycemia with progression to type 1 diabetes in the Diabetes Prevention Trial-Type 1 (DPT-1)

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AU - Skyler, Jay S

AU - Krischer, Jeffrey P.

AU - Greenbaum, Carla J.

AU - Mahon, Jeffrey

AU - Rafkin, Lisa

AU - Cuthbertson, David

AU - Cowie, Catherine

AU - Herold, Kevan

AU - Eisenbarth, George

AU - Palmer, Jerry P.

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N2 - OBJECTIVE - We characterized fluctuations between states of glycemia in progressors to type 1 diabetes and studied whether those fluctuations are related to the early C-peptide response to oral glucose. RESEARCH DESIGN AND METHODS - Oral glucose tolerance tests (OGTTs) from differing states of glycemia were compared within individuals for glucose and C-peptide. Dysglycemic OGTTs (DYSOGTTs) were compared with normal OGTTs (NLOGTT), while transient diabetic OGTTs (TDOGTTs) were compared with subsequent nondiabetic OGTTs and with OGTTs performed at diagnosis. RESULTS - Of 135 progressors with four or more OGTTs, 30 (22%) went from NLOGTTs to DYSOGTTs at least twice. Area under the curve (AUC) glucose values from the second NLOGTT were higher (P < 0.001) than values from the first NLOGTT. Among 98 progressors whose DYSOGTTs and NLOGTTs were synchronized for the time before diagnosis, despite higher glucose levels (P < 0.01 at all time points) in the DYSOGTTs, 30-to 0-min C-peptide difference values changed little. Likewise, 30-to 0-min C-peptide difference values did not differ between TDOGTTs and subsequent (within 3 months) nondiabetic OGTTs in 55 progressors. In contrast, as glucose levels increased overall from the first to last OGTTs before diagnosis (P < 0.001 at every time point, n = 207), 30- to 0-min C-peptide difference values decreased (P < 0.001). CONCLUSIONS - Glucose levels fluctuate widely as they gradually increase overall with progression to type 1 diabetes. As glucose levels increase, the early C-peptide response declines. In contrast, glucose fluctuations are not related to the early Cpeptide response. This suggests that changes in insulin sensitivity underlie the glucose fluctuations.

AB - OBJECTIVE - We characterized fluctuations between states of glycemia in progressors to type 1 diabetes and studied whether those fluctuations are related to the early C-peptide response to oral glucose. RESEARCH DESIGN AND METHODS - Oral glucose tolerance tests (OGTTs) from differing states of glycemia were compared within individuals for glucose and C-peptide. Dysglycemic OGTTs (DYSOGTTs) were compared with normal OGTTs (NLOGTT), while transient diabetic OGTTs (TDOGTTs) were compared with subsequent nondiabetic OGTTs and with OGTTs performed at diagnosis. RESULTS - Of 135 progressors with four or more OGTTs, 30 (22%) went from NLOGTTs to DYSOGTTs at least twice. Area under the curve (AUC) glucose values from the second NLOGTT were higher (P < 0.001) than values from the first NLOGTT. Among 98 progressors whose DYSOGTTs and NLOGTTs were synchronized for the time before diagnosis, despite higher glucose levels (P < 0.01 at all time points) in the DYSOGTTs, 30-to 0-min C-peptide difference values changed little. Likewise, 30-to 0-min C-peptide difference values did not differ between TDOGTTs and subsequent (within 3 months) nondiabetic OGTTs in 55 progressors. In contrast, as glucose levels increased overall from the first to last OGTTs before diagnosis (P < 0.001 at every time point, n = 207), 30- to 0-min C-peptide difference values decreased (P < 0.001). CONCLUSIONS - Glucose levels fluctuate widely as they gradually increase overall with progression to type 1 diabetes. As glucose levels increase, the early C-peptide response declines. In contrast, glucose fluctuations are not related to the early Cpeptide response. This suggests that changes in insulin sensitivity underlie the glucose fluctuations.

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