Endogenous incretin hormone augmentation of acute insulin secretion in normoglycemic relatives of type 2 diabetic subjects

a 10-year retrospective pathophysiological study

Frank P Alford, Christian Rantzau, Jan-Erik Henriksen, Mette Brogaard Egede, Tina Trier Durck, Klaus Levin, Henning Beck-Nielsen

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

AIMS/HYPOTHESIS: The pathophysiological role of gut incretin hormone argumentation on acute insulin release in the genesis of type 2 diabetes (TDM2) is uncertain. We examined retrospectively at 0 year and 10 years the endogenous incretin hormone action (IHA) on acute insulin release and glucose tolerance in normoglycemic relatives (REL) of TDM2 and control (CON) subjects.

METHODS: At 0 year and 10 years, glucose tolerance, paired oral glucose tolerance test (OGTT)- and i.v. glucose tolerance test (IVGTT)-induced acute (0-30 min) insulin release (insulinogenic index IGIOGTT and IGIIVGTT), and IHA were calculated in 19 REL and 18 CON subjects by cross-correlation linear regression slope analyses of the OGTT (0-30 min) matched insulin/glucose profiles vs the early (0-5 min) and delayed (10-30 min) IVGTT profiles.

RESULTS: At 0 year, REL and CON IGIOGTT and IGIIVGTT were similar, but the REL 2- to 5-min IVGTT-induced insulin responses were reduced (P < .03). By 10 years, glucose tolerance deteriorated in nine dysglycemic REL (RELDGT), with raised fasting glucose and 2-hour OGTT glucose. Retrospective analyses of RELDGT at 0 year demonstrated raised proinsulin/insulin molar ratios and fasting glucose and a reduced IVGTT insulin/glucose slope, but the RELDGT IHA was similar to normoglycemic REL (RELNGT) and CON. By 10 years, RELDGT OGTT insulin/glucose slopes were reduced (P = .03-.01), but more so for the early (P < .01-.003) and delayed (P < .005-.002) IVGTT slopes, compared to the normoglycaemic REL and CON subjects.

CONCLUSIONS: IHA on acute insulin release is maintained in normoglycemic REL and CON subjects over 10 years. The apparent deterioration in IHA in RELDGT is consistent with a progressive failure of acute β-cell function over 10 years.

OriginalsprogEngelsk
TidsskriftJournal of Clinical Endocrinology and Metabolism
Vol/bind99
Udgave nummer10
Sider (fra-til)E1943-50
ISSN0021-972X
DOI
StatusUdgivet - 2014

Fingeraftryk

Glucose Tolerance Test
Retrospective Studies
Hormones
Insulin
Fasting
Proinsulin
Type 2 Diabetes Mellitus
Linear Models
Regression Analysis

Citer dette

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title = "Endogenous incretin hormone augmentation of acute insulin secretion in normoglycemic relatives of type 2 diabetic subjects: a 10-year retrospective pathophysiological study",
abstract = "AIMS/HYPOTHESIS: The pathophysiological role of gut incretin hormone argumentation on acute insulin release in the genesis of type 2 diabetes (TDM2) is uncertain. We examined retrospectively at 0 year and 10 years the endogenous incretin hormone action (IHA) on acute insulin release and glucose tolerance in normoglycemic relatives (REL) of TDM2 and control (CON) subjects.METHODS: At 0 year and 10 years, glucose tolerance, paired oral glucose tolerance test (OGTT)- and i.v. glucose tolerance test (IVGTT)-induced acute (0-30 min) insulin release (insulinogenic index IGIOGTT and IGIIVGTT), and IHA were calculated in 19 REL and 18 CON subjects by cross-correlation linear regression slope analyses of the OGTT (0-30 min) matched insulin/glucose profiles vs the early (0-5 min) and delayed (10-30 min) IVGTT profiles.RESULTS: At 0 year, REL and CON IGIOGTT and IGIIVGTT were similar, but the REL 2- to 5-min IVGTT-induced insulin responses were reduced (P < .03). By 10 years, glucose tolerance deteriorated in nine dysglycemic REL (RELDGT), with raised fasting glucose and 2-hour OGTT glucose. Retrospective analyses of RELDGT at 0 year demonstrated raised proinsulin/insulin molar ratios and fasting glucose and a reduced IVGTT insulin/glucose slope, but the RELDGT IHA was similar to normoglycemic REL (RELNGT) and CON. By 10 years, RELDGT OGTT insulin/glucose slopes were reduced (P = .03-.01), but more so for the early (P < .01-.003) and delayed (P < .005-.002) IVGTT slopes, compared to the normoglycaemic REL and CON subjects.CONCLUSIONS: IHA on acute insulin release is maintained in normoglycemic REL and CON subjects over 10 years. The apparent deterioration in IHA in RELDGT is consistent with a progressive failure of acute β-cell function over 10 years.",
author = "Alford, {Frank P} and Christian Rantzau and Jan-Erik Henriksen and Egede, {Mette Brogaard} and Durck, {Tina Trier} and Klaus Levin and Henning Beck-Nielsen",
year = "2014",
doi = "10.1210/jc.2014-1644",
language = "English",
volume = "99",
pages = "E1943--50",
journal = "Journal of Clinical Endocrinology and Metabolism",
issn = "0021-972X",
publisher = "Heinemann",
number = "10",

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Endogenous incretin hormone augmentation of acute insulin secretion in normoglycemic relatives of type 2 diabetic subjects : a 10-year retrospective pathophysiological study. / Alford, Frank P; Rantzau, Christian; Henriksen, Jan-Erik; Egede, Mette Brogaard; Durck, Tina Trier; Levin, Klaus; Beck-Nielsen, Henning.

I: Journal of Clinical Endocrinology and Metabolism, Bind 99, Nr. 10, 2014, s. E1943-50.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Endogenous incretin hormone augmentation of acute insulin secretion in normoglycemic relatives of type 2 diabetic subjects

T2 - a 10-year retrospective pathophysiological study

AU - Alford, Frank P

AU - Rantzau, Christian

AU - Henriksen, Jan-Erik

AU - Egede, Mette Brogaard

AU - Durck, Tina Trier

AU - Levin, Klaus

AU - Beck-Nielsen, Henning

PY - 2014

Y1 - 2014

N2 - AIMS/HYPOTHESIS: The pathophysiological role of gut incretin hormone argumentation on acute insulin release in the genesis of type 2 diabetes (TDM2) is uncertain. We examined retrospectively at 0 year and 10 years the endogenous incretin hormone action (IHA) on acute insulin release and glucose tolerance in normoglycemic relatives (REL) of TDM2 and control (CON) subjects.METHODS: At 0 year and 10 years, glucose tolerance, paired oral glucose tolerance test (OGTT)- and i.v. glucose tolerance test (IVGTT)-induced acute (0-30 min) insulin release (insulinogenic index IGIOGTT and IGIIVGTT), and IHA were calculated in 19 REL and 18 CON subjects by cross-correlation linear regression slope analyses of the OGTT (0-30 min) matched insulin/glucose profiles vs the early (0-5 min) and delayed (10-30 min) IVGTT profiles.RESULTS: At 0 year, REL and CON IGIOGTT and IGIIVGTT were similar, but the REL 2- to 5-min IVGTT-induced insulin responses were reduced (P < .03). By 10 years, glucose tolerance deteriorated in nine dysglycemic REL (RELDGT), with raised fasting glucose and 2-hour OGTT glucose. Retrospective analyses of RELDGT at 0 year demonstrated raised proinsulin/insulin molar ratios and fasting glucose and a reduced IVGTT insulin/glucose slope, but the RELDGT IHA was similar to normoglycemic REL (RELNGT) and CON. By 10 years, RELDGT OGTT insulin/glucose slopes were reduced (P = .03-.01), but more so for the early (P < .01-.003) and delayed (P < .005-.002) IVGTT slopes, compared to the normoglycaemic REL and CON subjects.CONCLUSIONS: IHA on acute insulin release is maintained in normoglycemic REL and CON subjects over 10 years. The apparent deterioration in IHA in RELDGT is consistent with a progressive failure of acute β-cell function over 10 years.

AB - AIMS/HYPOTHESIS: The pathophysiological role of gut incretin hormone argumentation on acute insulin release in the genesis of type 2 diabetes (TDM2) is uncertain. We examined retrospectively at 0 year and 10 years the endogenous incretin hormone action (IHA) on acute insulin release and glucose tolerance in normoglycemic relatives (REL) of TDM2 and control (CON) subjects.METHODS: At 0 year and 10 years, glucose tolerance, paired oral glucose tolerance test (OGTT)- and i.v. glucose tolerance test (IVGTT)-induced acute (0-30 min) insulin release (insulinogenic index IGIOGTT and IGIIVGTT), and IHA were calculated in 19 REL and 18 CON subjects by cross-correlation linear regression slope analyses of the OGTT (0-30 min) matched insulin/glucose profiles vs the early (0-5 min) and delayed (10-30 min) IVGTT profiles.RESULTS: At 0 year, REL and CON IGIOGTT and IGIIVGTT were similar, but the REL 2- to 5-min IVGTT-induced insulin responses were reduced (P < .03). By 10 years, glucose tolerance deteriorated in nine dysglycemic REL (RELDGT), with raised fasting glucose and 2-hour OGTT glucose. Retrospective analyses of RELDGT at 0 year demonstrated raised proinsulin/insulin molar ratios and fasting glucose and a reduced IVGTT insulin/glucose slope, but the RELDGT IHA was similar to normoglycemic REL (RELNGT) and CON. By 10 years, RELDGT OGTT insulin/glucose slopes were reduced (P = .03-.01), but more so for the early (P < .01-.003) and delayed (P < .005-.002) IVGTT slopes, compared to the normoglycaemic REL and CON subjects.CONCLUSIONS: IHA on acute insulin release is maintained in normoglycemic REL and CON subjects over 10 years. The apparent deterioration in IHA in RELDGT is consistent with a progressive failure of acute β-cell function over 10 years.

U2 - 10.1210/jc.2014-1644

DO - 10.1210/jc.2014-1644

M3 - Journal article

VL - 99

SP - E1943-50

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 10

ER -