Processes Underlying Glycemic Deterioration in Type 2 Diabetes: An IMI DIRECT Study

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Standard

Processes Underlying Glycemic Deterioration in Type 2 Diabetes : An IMI DIRECT Study. / Bizzotto, Roberto; Jennison, Christopher; Jones, Angus G.; Kurbasic, Azra; Tura, Andrea; Kennedy, Gwen; Bell, Jimmy D.; Thomas, E. Louise; Frost, Gary; Eriksen, Rebeca; Koivula, Robert W.; Brage, Soren; Kaye, Jane; Hattersley, Andrew T.; Heggie, Alison; McEvoy, Donna; 't Hart, Leen M.; Beulens, Joline W.; Elders, Petra; Musholt, Petra B.; Ridderstrale, Martin; Hansen, Tue H.; Allin, Kristine H.; Hansen, Torben; Vestergaard, Henrik; Lundgaard, Agnete T.; Thomsen, Henrik S.; De Masi, Federico; Tsirigos, Konstantinos D.; Brunak, Søren; Vinuela, Ana; Mahajan, Anubha; McDonald, Timothy J.; Kokkola, Tarja; Forgie, Ian M.; Giordano, Giuseppe N.; Pavo, Imre; Ruetten, Hartmut; Dermitzakis, Emmanouil; McCarthy, Mark I.; Pedersen, Oluf; Schwenk, Jochen M.; Adamski, Jerzy; Franks, Paul W.; Walker, Mark; Pearson, Ewan R.; Mari, Andrea; IMI-DIRECT consortium.

In: Diabetes Care, Vol. 44, No. 2, 2021, p. 511-518.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Bizzotto, R, Jennison, C, Jones, AG, Kurbasic, A, Tura, A, Kennedy, G, Bell, JD, Thomas, EL, Frost, G, Eriksen, R, Koivula, RW, Brage, S, Kaye, J, Hattersley, AT, Heggie, A, McEvoy, D, 't Hart, LM, Beulens, JW, Elders, P, Musholt, PB, Ridderstrale, M, Hansen, TH, Allin, KH, Hansen, T, Vestergaard, H, Lundgaard, AT, Thomsen, HS, De Masi, F, Tsirigos, KD, Brunak, S, Vinuela, A, Mahajan, A, McDonald, TJ, Kokkola, T, Forgie, IM, Giordano, GN, Pavo, I, Ruetten, H, Dermitzakis, E, McCarthy, MI, Pedersen, O, Schwenk, JM, Adamski, J, Franks, PW, Walker, M, Pearson, ER, Mari, A & IMI-DIRECT consortium 2021, 'Processes Underlying Glycemic Deterioration in Type 2 Diabetes: An IMI DIRECT Study', Diabetes Care, vol. 44, no. 2, pp. 511-518. https://doi.org/10.2337/dc20-1567

APA

Bizzotto, R., Jennison, C., Jones, A. G., Kurbasic, A., Tura, A., Kennedy, G., Bell, J. D., Thomas, E. L., Frost, G., Eriksen, R., Koivula, R. W., Brage, S., Kaye, J., Hattersley, A. T., Heggie, A., McEvoy, D., 't Hart, L. M., Beulens, J. W., Elders, P., ... IMI-DIRECT consortium (2021). Processes Underlying Glycemic Deterioration in Type 2 Diabetes: An IMI DIRECT Study. Diabetes Care, 44(2), 511-518. https://doi.org/10.2337/dc20-1567

Vancouver

Bizzotto R, Jennison C, Jones AG, Kurbasic A, Tura A, Kennedy G et al. Processes Underlying Glycemic Deterioration in Type 2 Diabetes: An IMI DIRECT Study. Diabetes Care. 2021;44(2):511-518. https://doi.org/10.2337/dc20-1567

Author

Bizzotto, Roberto ; Jennison, Christopher ; Jones, Angus G. ; Kurbasic, Azra ; Tura, Andrea ; Kennedy, Gwen ; Bell, Jimmy D. ; Thomas, E. Louise ; Frost, Gary ; Eriksen, Rebeca ; Koivula, Robert W. ; Brage, Soren ; Kaye, Jane ; Hattersley, Andrew T. ; Heggie, Alison ; McEvoy, Donna ; 't Hart, Leen M. ; Beulens, Joline W. ; Elders, Petra ; Musholt, Petra B. ; Ridderstrale, Martin ; Hansen, Tue H. ; Allin, Kristine H. ; Hansen, Torben ; Vestergaard, Henrik ; Lundgaard, Agnete T. ; Thomsen, Henrik S. ; De Masi, Federico ; Tsirigos, Konstantinos D. ; Brunak, Søren ; Vinuela, Ana ; Mahajan, Anubha ; McDonald, Timothy J. ; Kokkola, Tarja ; Forgie, Ian M. ; Giordano, Giuseppe N. ; Pavo, Imre ; Ruetten, Hartmut ; Dermitzakis, Emmanouil ; McCarthy, Mark I. ; Pedersen, Oluf ; Schwenk, Jochen M. ; Adamski, Jerzy ; Franks, Paul W. ; Walker, Mark ; Pearson, Ewan R. ; Mari, Andrea ; IMI-DIRECT consortium. / Processes Underlying Glycemic Deterioration in Type 2 Diabetes : An IMI DIRECT Study. In: Diabetes Care. 2021 ; Vol. 44, No. 2. pp. 511-518.

Bibtex

@article{cb858584067a4d4087711c49be3fb3df,
title = "Processes Underlying Glycemic Deterioration in Type 2 Diabetes: An IMI DIRECT Study",
abstract = "OBJECTIVEWe investigated the processes underlying glycemic deterioration in type 2 diabetes (T2D).RESEARCH DESIGN AND METHODSA total of 732 recently diagnosed patients with T2D from the Innovative Medicines Initiative Diabetes Research on Patient Stratification (IMI DIRECT) study were extensively phenotyped over 3 years, including measures of insulin sensitivity (OGIS), beta-cell glucose sensitivity (GS), and insulin clearance (CLIm) from mixed meal tests, liver enzymes, lipid profiles, and baseline regional fat from MRI. The associations between the longitudinal metabolic patterns and HbA(1c) deterioration, adjusted for changes in BMI and in diabetes medications, were assessed via stepwise multivariable linear and logistic regression.RESULTSFaster HbA(1c) progression was independently associated with faster deterioration of OGIS and GS and increasing CLIm; visceral or liver fat, HDL-cholesterol, and triglycerides had further independent, though weaker, roles (R-2 = 0.38). A subgroup of patients with a markedly higher progression rate (fast progressors) was clearly distinguishable considering these variables only (discrimination capacity from area under the receiver operating characteristic = 0.94). The proportion of fast progressors was reduced from 56% to 8-10% in subgroups in which only one trait among OGIS, GS, and CLIm was relatively stable (odds ratios 0.07-0.09). T2D polygenic risk score and baseline pancreatic fat, glucagon-like peptide 1, glucagon, diet, and physical activity did not show an independent role.CONCLUSIONSDeteriorating insulin sensitivity and beta-cell function, increasing insulin clearance, high visceral or liver fat, and worsening of the lipid profile are the crucial factors mediating glycemic deterioration of patients with T2D in the initial phase of the disease. Stabilization of a single trait among insulin sensitivity, beta-cell function, and insulin clearance may be relevant to prevent progression.",
keywords = "BETA-CELL FUNCTION, ASSESSING INSULIN SENSITIVITY, RESISTANCE, PROGRESSION, SECRETION, ROSIGLITAZONE, TRIGLYCERIDES, POPULATION, CLEARANCE, GLYBURIDE",
author = "Roberto Bizzotto and Christopher Jennison and Jones, {Angus G.} and Azra Kurbasic and Andrea Tura and Gwen Kennedy and Bell, {Jimmy D.} and Thomas, {E. Louise} and Gary Frost and Rebeca Eriksen and Koivula, {Robert W.} and Soren Brage and Jane Kaye and Hattersley, {Andrew T.} and Alison Heggie and Donna McEvoy and {'t Hart}, {Leen M.} and Beulens, {Joline W.} and Petra Elders and Musholt, {Petra B.} and Martin Ridderstrale and Hansen, {Tue H.} and Allin, {Kristine H.} and Torben Hansen and Henrik Vestergaard and Lundgaard, {Agnete T.} and Thomsen, {Henrik S.} and {De Masi}, Federico and Tsirigos, {Konstantinos D.} and S{\o}ren Brunak and Ana Vinuela and Anubha Mahajan and McDonald, {Timothy J.} and Tarja Kokkola and Forgie, {Ian M.} and Giordano, {Giuseppe N.} and Imre Pavo and Hartmut Ruetten and Emmanouil Dermitzakis and McCarthy, {Mark I.} and Oluf Pedersen and Schwenk, {Jochen M.} and Jerzy Adamski and Franks, {Paul W.} and Mark Walker and Pearson, {Ewan R.} and Andrea Mari and {IMI-DIRECT consortium}",
year = "2021",
doi = "10.2337/dc20-1567",
language = "English",
volume = "44",
pages = "511--518",
journal = "Diabetes Care",
issn = "0149-5992",
publisher = "American Diabetes Association",
number = "2",

}

RIS

TY - JOUR

T1 - Processes Underlying Glycemic Deterioration in Type 2 Diabetes

T2 - An IMI DIRECT Study

AU - Bizzotto, Roberto

AU - Jennison, Christopher

AU - Jones, Angus G.

AU - Kurbasic, Azra

AU - Tura, Andrea

AU - Kennedy, Gwen

AU - Bell, Jimmy D.

AU - Thomas, E. Louise

AU - Frost, Gary

AU - Eriksen, Rebeca

AU - Koivula, Robert W.

AU - Brage, Soren

AU - Kaye, Jane

AU - Hattersley, Andrew T.

AU - Heggie, Alison

AU - McEvoy, Donna

AU - 't Hart, Leen M.

AU - Beulens, Joline W.

AU - Elders, Petra

AU - Musholt, Petra B.

AU - Ridderstrale, Martin

AU - Hansen, Tue H.

AU - Allin, Kristine H.

AU - Hansen, Torben

AU - Vestergaard, Henrik

AU - Lundgaard, Agnete T.

AU - Thomsen, Henrik S.

AU - De Masi, Federico

AU - Tsirigos, Konstantinos D.

AU - Brunak, Søren

AU - Vinuela, Ana

AU - Mahajan, Anubha

AU - McDonald, Timothy J.

AU - Kokkola, Tarja

AU - Forgie, Ian M.

AU - Giordano, Giuseppe N.

AU - Pavo, Imre

AU - Ruetten, Hartmut

AU - Dermitzakis, Emmanouil

AU - McCarthy, Mark I.

AU - Pedersen, Oluf

AU - Schwenk, Jochen M.

AU - Adamski, Jerzy

AU - Franks, Paul W.

AU - Walker, Mark

AU - Pearson, Ewan R.

AU - Mari, Andrea

AU - IMI-DIRECT consortium

PY - 2021

Y1 - 2021

N2 - OBJECTIVEWe investigated the processes underlying glycemic deterioration in type 2 diabetes (T2D).RESEARCH DESIGN AND METHODSA total of 732 recently diagnosed patients with T2D from the Innovative Medicines Initiative Diabetes Research on Patient Stratification (IMI DIRECT) study were extensively phenotyped over 3 years, including measures of insulin sensitivity (OGIS), beta-cell glucose sensitivity (GS), and insulin clearance (CLIm) from mixed meal tests, liver enzymes, lipid profiles, and baseline regional fat from MRI. The associations between the longitudinal metabolic patterns and HbA(1c) deterioration, adjusted for changes in BMI and in diabetes medications, were assessed via stepwise multivariable linear and logistic regression.RESULTSFaster HbA(1c) progression was independently associated with faster deterioration of OGIS and GS and increasing CLIm; visceral or liver fat, HDL-cholesterol, and triglycerides had further independent, though weaker, roles (R-2 = 0.38). A subgroup of patients with a markedly higher progression rate (fast progressors) was clearly distinguishable considering these variables only (discrimination capacity from area under the receiver operating characteristic = 0.94). The proportion of fast progressors was reduced from 56% to 8-10% in subgroups in which only one trait among OGIS, GS, and CLIm was relatively stable (odds ratios 0.07-0.09). T2D polygenic risk score and baseline pancreatic fat, glucagon-like peptide 1, glucagon, diet, and physical activity did not show an independent role.CONCLUSIONSDeteriorating insulin sensitivity and beta-cell function, increasing insulin clearance, high visceral or liver fat, and worsening of the lipid profile are the crucial factors mediating glycemic deterioration of patients with T2D in the initial phase of the disease. Stabilization of a single trait among insulin sensitivity, beta-cell function, and insulin clearance may be relevant to prevent progression.

AB - OBJECTIVEWe investigated the processes underlying glycemic deterioration in type 2 diabetes (T2D).RESEARCH DESIGN AND METHODSA total of 732 recently diagnosed patients with T2D from the Innovative Medicines Initiative Diabetes Research on Patient Stratification (IMI DIRECT) study were extensively phenotyped over 3 years, including measures of insulin sensitivity (OGIS), beta-cell glucose sensitivity (GS), and insulin clearance (CLIm) from mixed meal tests, liver enzymes, lipid profiles, and baseline regional fat from MRI. The associations between the longitudinal metabolic patterns and HbA(1c) deterioration, adjusted for changes in BMI and in diabetes medications, were assessed via stepwise multivariable linear and logistic regression.RESULTSFaster HbA(1c) progression was independently associated with faster deterioration of OGIS and GS and increasing CLIm; visceral or liver fat, HDL-cholesterol, and triglycerides had further independent, though weaker, roles (R-2 = 0.38). A subgroup of patients with a markedly higher progression rate (fast progressors) was clearly distinguishable considering these variables only (discrimination capacity from area under the receiver operating characteristic = 0.94). The proportion of fast progressors was reduced from 56% to 8-10% in subgroups in which only one trait among OGIS, GS, and CLIm was relatively stable (odds ratios 0.07-0.09). T2D polygenic risk score and baseline pancreatic fat, glucagon-like peptide 1, glucagon, diet, and physical activity did not show an independent role.CONCLUSIONSDeteriorating insulin sensitivity and beta-cell function, increasing insulin clearance, high visceral or liver fat, and worsening of the lipid profile are the crucial factors mediating glycemic deterioration of patients with T2D in the initial phase of the disease. Stabilization of a single trait among insulin sensitivity, beta-cell function, and insulin clearance may be relevant to prevent progression.

KW - BETA-CELL FUNCTION

KW - ASSESSING INSULIN SENSITIVITY

KW - RESISTANCE

KW - PROGRESSION

KW - SECRETION

KW - ROSIGLITAZONE

KW - TRIGLYCERIDES

KW - POPULATION

KW - CLEARANCE

KW - GLYBURIDE

U2 - 10.2337/dc20-1567

DO - 10.2337/dc20-1567

M3 - Journal article

C2 - 33323478

VL - 44

SP - 511

EP - 518

JO - Diabetes Care

JF - Diabetes Care

SN - 0149-5992

IS - 2

ER -

ID: 256327710