Long-Term Complications in Youth-Onset Type 2 Diabetes

A clinical trial assessed the efficacy of three treatments, all involving metformin, on glycemic control in youth-onset type 2 diabetes. This follow-up study shows that the risk of complications increased steadily over time, and complications developed in most participants by young adulthood.

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Bibliographic Details
Published inThe New England journal of medicine Vol. 385; no. 5; pp. 416 - 426
Main Authors Bjornstad, Petter, Drews, Kimberly L, Caprio, Sonia, Gubitosi-Klug, Rose, Nathan, David M, Tesfaldet, Bereket, Tryggestad, Jeanie, White, Neil H, Zeitler, Philip
Format Journal Article
LanguageEnglish
Published United States Massachusetts Medical Society 29.07.2021
Subjects
Online AccessGet full text
ISSN0028-4793
1533-4406
1533-4406
DOI10.1056/NEJMoa2100165

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Abstract A clinical trial assessed the efficacy of three treatments, all involving metformin, on glycemic control in youth-onset type 2 diabetes. This follow-up study shows that the risk of complications increased steadily over time, and complications developed in most participants by young adulthood.
AbstractList A clinical trial assessed the efficacy of three treatments, all involving metformin, on glycemic control in youth-onset type 2 diabetes. This follow-up study shows that the risk of complications increased steadily over time, and complications developed in most participants by young adulthood.
The prevalence of type 2 diabetes in youth is increasing, but little is known regarding the occurrence of related complications as these youths transition to adulthood.BACKGROUNDThe prevalence of type 2 diabetes in youth is increasing, but little is known regarding the occurrence of related complications as these youths transition to adulthood.We previously conducted a multicenter clinical trial (from 2004 to 2011) to evaluate the effects of one of three treatments (metformin, metformin plus rosiglitazone, or metformin plus an intensive lifestyle intervention) on the time to loss of glycemic control in participants who had onset of type 2 diabetes in youth. After completion of the trial, participants were transitioned to metformin with or without insulin and were enrolled in an observational follow-up study (performed from 2011 to 2020), which was conducted in two phases; the results of this follow-up study are reported here. Assessments for diabetic kidney disease, hypertension, dyslipidemia, and nerve disease were performed annually, and assessments for retinal disease were performed twice. Complications related to diabetes identified outside the study were confirmed and adjudicated.METHODSWe previously conducted a multicenter clinical trial (from 2004 to 2011) to evaluate the effects of one of three treatments (metformin, metformin plus rosiglitazone, or metformin plus an intensive lifestyle intervention) on the time to loss of glycemic control in participants who had onset of type 2 diabetes in youth. After completion of the trial, participants were transitioned to metformin with or without insulin and were enrolled in an observational follow-up study (performed from 2011 to 2020), which was conducted in two phases; the results of this follow-up study are reported here. Assessments for diabetic kidney disease, hypertension, dyslipidemia, and nerve disease were performed annually, and assessments for retinal disease were performed twice. Complications related to diabetes identified outside the study were confirmed and adjudicated.At the end of the second phase of the follow-up study (January 2020), the mean (±SD) age of the 500 participants who were included in the analyses was 26.4±2.8 years, and the mean time since the diagnosis of diabetes was 13.3±1.8 years. The cumulative incidence of hypertension was 67.5%, the incidence of dyslipidemia was 51.6%, the incidence of diabetic kidney disease was 54.8%, and the incidence of nerve disease was 32.4%. The prevalence of retinal disease, including more advanced stages, was 13.7% in the period from 2010 to 2011 and 51.0% in the period from 2017 to 2018. At least one complication occurred in 60.1% of the participants, and at least two complications occurred in 28.4%. Risk factors for the development of complications included minority race or ethnic group, hyperglycemia, hypertension, and dyslipidemia. No adverse events were recorded during follow-up.RESULTSAt the end of the second phase of the follow-up study (January 2020), the mean (±SD) age of the 500 participants who were included in the analyses was 26.4±2.8 years, and the mean time since the diagnosis of diabetes was 13.3±1.8 years. The cumulative incidence of hypertension was 67.5%, the incidence of dyslipidemia was 51.6%, the incidence of diabetic kidney disease was 54.8%, and the incidence of nerve disease was 32.4%. The prevalence of retinal disease, including more advanced stages, was 13.7% in the period from 2010 to 2011 and 51.0% in the period from 2017 to 2018. At least one complication occurred in 60.1% of the participants, and at least two complications occurred in 28.4%. Risk factors for the development of complications included minority race or ethnic group, hyperglycemia, hypertension, and dyslipidemia. No adverse events were recorded during follow-up.Among participants who had onset of type 2 diabetes in youth, the risk of complications, including microvascular complications, increased steadily over time and affected most participants by the time of young adulthood. Complications were more common among participants of minority race and ethnic group and among those with hyperglycemia, hypertension, and dyslipidemia. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; ClinicalTrials.gov numbers, NCT01364350 and NCT02310724.).CONCLUSIONSAmong participants who had onset of type 2 diabetes in youth, the risk of complications, including microvascular complications, increased steadily over time and affected most participants by the time of young adulthood. Complications were more common among participants of minority race and ethnic group and among those with hyperglycemia, hypertension, and dyslipidemia. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; ClinicalTrials.gov numbers, NCT01364350 and NCT02310724.).
AbstractBackgroundThe prevalence of type 2 diabetes in youth is increasing, but little is known regarding the occurrence of related complications as these youths transition to adulthood.MethodsWe previously conducted a multicenter clinical trial (from 2004 to 2011) to evaluate the effects of one of three treatments (metformin, metformin plus rosiglitazone, or metformin plus an intensive lifestyle intervention) on the time to loss of glycemic control in participants who had onset of type 2 diabetes in youth. After completion of the trial, participants were transitioned to metformin with or without insulin and were enrolled in an observational follow-up study (performed from 2011 to 2020), which was conducted in two phases; the results of this follow-up study are reported here. Assessments for diabetic kidney disease, hypertension, dyslipidemia, and nerve disease were performed annually, and assessments for retinal disease were performed twice. Complications related to diabetes identified outside the study were confirmed and adjudicated.ResultsAt the end of the second phase of the follow-up study (January 2020), the mean (±SD) age of the 500 participants who were included in the analyses was 26.4±2.8 years, and the mean time since the diagnosis of diabetes was 13.3±1.8 years. The cumulative incidence of hypertension was 67.5%, the incidence of dyslipidemia was 51.6%, the incidence of diabetic kidney disease was 54.8%, and the incidence of nerve disease was 32.4%. The prevalence of retinal disease, including more advanced stages, was 13.7% in the period from 2010 to 2011 and 51.0% in the period from 2017 to 2018. At least one complication occurred in 60.1% of the participants, and at least two complications occurred in 28.4%. Risk factors for the development of complications included minority race or ethnic group, hyperglycemia, hypertension, and dyslipidemia. No adverse events were recorded during follow-up.ConclusionsAmong participants who had onset of type 2 diabetes in youth, the risk of complications, including microvascular complications, increased steadily over time and affected most participants by the time of young adulthood. Complications were more common among participants of minority race and ethnic group and among those with hyperglycemia, hypertension, and dyslipidemia. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; ClinicalTrials.gov numbers, NCT01364350 and NCT02310724.)
The prevalence of type 2 diabetes in youth is increasing, but little is known regarding the occurrence of related complications as these youths transition to adulthood. We previously conducted a multicenter clinical trial (from 2004 to 2011) to evaluate the effects of one of three treatments (metformin, metformin plus rosiglitazone, or metformin plus an intensive lifestyle intervention) on the time to loss of glycemic control in participants who had onset of type 2 diabetes in youth. After completion of the trial, participants were transitioned to metformin with or without insulin and were enrolled in an observational follow-up study (performed from 2011 to 2020), which was conducted in two phases; the results of this follow-up study are reported here. Assessments for diabetic kidney disease, hypertension, dyslipidemia, and nerve disease were performed annually, and assessments for retinal disease were performed twice. Complications related to diabetes identified outside the study were confirmed and adjudicated. At the end of the second phase of the follow-up study (January 2020), the mean (±SD) age of the 500 participants who were included in the analyses was 26.4±2.8 years, and the mean time since the diagnosis of diabetes was 13.3±1.8 years. The cumulative incidence of hypertension was 67.5%, the incidence of dyslipidemia was 51.6%, the incidence of diabetic kidney disease was 54.8%, and the incidence of nerve disease was 32.4%. The prevalence of retinal disease, including more advanced stages, was 13.7% in the period from 2010 to 2011 and 51.0% in the period from 2017 to 2018. At least one complication occurred in 60.1% of the participants, and at least two complications occurred in 28.4%. Risk factors for the development of complications included minority race or ethnic group, hyperglycemia, hypertension, and dyslipidemia. No adverse events were recorded during follow-up. Among participants who had onset of type 2 diabetes in youth, the risk of complications, including microvascular complications, increased steadily over time and affected most participants by the time of young adulthood. Complications were more common among participants of minority race and ethnic group and among those with hyperglycemia, hypertension, and dyslipidemia. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; ClinicalTrials.gov numbers, NCT01364350 and NCT02310724.).
Author Tryggestad, Jeanie
Zeitler, Philip
Drews, Kimberly L
Caprio, Sonia
Nathan, David M
Tesfaldet, Bereket
White, Neil H
Gubitosi-Klug, Rose
Bjornstad, Petter
Author_xml – sequence: 1
  givenname: Petter
  surname: Bjornstad
  fullname: Bjornstad, Petter
  organization: From the University of Colorado Anschutz Medical Campus, Children's Hospital Colorado, Aurora (P.B., P.Z.); George Washington University, Rockville, MD (K.L.D., B.T.); Yale University, New Haven, CT (S.C.); Case Western Reserve University, Rainbow Babies and Children's Hospital, Cleveland (R.G.-K.); the Massachusetts General Hospital Diabetes Center, Harvard Medical School, Boston (D.M.N.); the University of Oklahoma Health Sciences Center, Oklahoma City (J.T.); and Washington University School of Medicine, St. Louis (N.H.W.)
– sequence: 2
  givenname: Kimberly L
  orcidid: 0000-0001-9287-2540
  surname: Drews
  fullname: Drews, Kimberly L
  organization: From the University of Colorado Anschutz Medical Campus, Children's Hospital Colorado, Aurora (P.B., P.Z.); George Washington University, Rockville, MD (K.L.D., B.T.); Yale University, New Haven, CT (S.C.); Case Western Reserve University, Rainbow Babies and Children's Hospital, Cleveland (R.G.-K.); the Massachusetts General Hospital Diabetes Center, Harvard Medical School, Boston (D.M.N.); the University of Oklahoma Health Sciences Center, Oklahoma City (J.T.); and Washington University School of Medicine, St. Louis (N.H.W.)
– sequence: 3
  givenname: Sonia
  surname: Caprio
  fullname: Caprio, Sonia
  organization: From the University of Colorado Anschutz Medical Campus, Children's Hospital Colorado, Aurora (P.B., P.Z.); George Washington University, Rockville, MD (K.L.D., B.T.); Yale University, New Haven, CT (S.C.); Case Western Reserve University, Rainbow Babies and Children's Hospital, Cleveland (R.G.-K.); the Massachusetts General Hospital Diabetes Center, Harvard Medical School, Boston (D.M.N.); the University of Oklahoma Health Sciences Center, Oklahoma City (J.T.); and Washington University School of Medicine, St. Louis (N.H.W.)
– sequence: 4
  givenname: Rose
  surname: Gubitosi-Klug
  fullname: Gubitosi-Klug, Rose
  organization: From the University of Colorado Anschutz Medical Campus, Children's Hospital Colorado, Aurora (P.B., P.Z.); George Washington University, Rockville, MD (K.L.D., B.T.); Yale University, New Haven, CT (S.C.); Case Western Reserve University, Rainbow Babies and Children's Hospital, Cleveland (R.G.-K.); the Massachusetts General Hospital Diabetes Center, Harvard Medical School, Boston (D.M.N.); the University of Oklahoma Health Sciences Center, Oklahoma City (J.T.); and Washington University School of Medicine, St. Louis (N.H.W.)
– sequence: 5
  givenname: David M
  surname: Nathan
  fullname: Nathan, David M
  organization: From the University of Colorado Anschutz Medical Campus, Children's Hospital Colorado, Aurora (P.B., P.Z.); George Washington University, Rockville, MD (K.L.D., B.T.); Yale University, New Haven, CT (S.C.); Case Western Reserve University, Rainbow Babies and Children's Hospital, Cleveland (R.G.-K.); the Massachusetts General Hospital Diabetes Center, Harvard Medical School, Boston (D.M.N.); the University of Oklahoma Health Sciences Center, Oklahoma City (J.T.); and Washington University School of Medicine, St. Louis (N.H.W.)
– sequence: 6
  givenname: Bereket
  surname: Tesfaldet
  fullname: Tesfaldet, Bereket
  organization: From the University of Colorado Anschutz Medical Campus, Children's Hospital Colorado, Aurora (P.B., P.Z.); George Washington University, Rockville, MD (K.L.D., B.T.); Yale University, New Haven, CT (S.C.); Case Western Reserve University, Rainbow Babies and Children's Hospital, Cleveland (R.G.-K.); the Massachusetts General Hospital Diabetes Center, Harvard Medical School, Boston (D.M.N.); the University of Oklahoma Health Sciences Center, Oklahoma City (J.T.); and Washington University School of Medicine, St. Louis (N.H.W.)
– sequence: 7
  givenname: Jeanie
  surname: Tryggestad
  fullname: Tryggestad, Jeanie
  organization: From the University of Colorado Anschutz Medical Campus, Children's Hospital Colorado, Aurora (P.B., P.Z.); George Washington University, Rockville, MD (K.L.D., B.T.); Yale University, New Haven, CT (S.C.); Case Western Reserve University, Rainbow Babies and Children's Hospital, Cleveland (R.G.-K.); the Massachusetts General Hospital Diabetes Center, Harvard Medical School, Boston (D.M.N.); the University of Oklahoma Health Sciences Center, Oklahoma City (J.T.); and Washington University School of Medicine, St. Louis (N.H.W.)
– sequence: 8
  givenname: Neil H
  surname: White
  fullname: White, Neil H
  organization: From the University of Colorado Anschutz Medical Campus, Children's Hospital Colorado, Aurora (P.B., P.Z.); George Washington University, Rockville, MD (K.L.D., B.T.); Yale University, New Haven, CT (S.C.); Case Western Reserve University, Rainbow Babies and Children's Hospital, Cleveland (R.G.-K.); the Massachusetts General Hospital Diabetes Center, Harvard Medical School, Boston (D.M.N.); the University of Oklahoma Health Sciences Center, Oklahoma City (J.T.); and Washington University School of Medicine, St. Louis (N.H.W.)
– sequence: 9
  givenname: Philip
  surname: Zeitler
  fullname: Zeitler, Philip
  organization: From the University of Colorado Anschutz Medical Campus, Children's Hospital Colorado, Aurora (P.B., P.Z.); George Washington University, Rockville, MD (K.L.D., B.T.); Yale University, New Haven, CT (S.C.); Case Western Reserve University, Rainbow Babies and Children's Hospital, Cleveland (R.G.-K.); the Massachusetts General Hospital Diabetes Center, Harvard Medical School, Boston (D.M.N.); the University of Oklahoma Health Sciences Center, Oklahoma City (J.T.); and Washington University School of Medicine, St. Louis (N.H.W.)
BackLink https://www.ncbi.nlm.nih.gov/pubmed/34320286$$D View this record in MEDLINE/PubMed
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ContentType Journal Article
Contributor Ward, A
Keating, C
Lipman, T
Hall, M
Goland, R
Zagado, R
Schwartzman, B
Venditti, E
Xu, Y K
Lassiter, C
McGuigan, P
Goebel-Fabbri, A
Jones, S M
Shah, R
Kaminski, B
Willi, S
Hughan, K
Marcus, M
Narasimhan, S
Libman, I
Songer, T
Brown, K
Chang, N
Koontz, M
Chao, L
Galvin, B
Ovalles, M
Flint, A
Gubitosi-Klug, R
Gallagher, D
Fleury-Milfort, E
Cuttler, L
Kringas, P
MacLeish, S
Kaufman, F
Anderson, B
McGirk, S
Bednarz, L
Gandica, R
Abrams, E
McGinley, G
Covington, G
Hollen, B
Laffel, L
Seributra, S
Gumpel, K
Bacha, F
Hausheer, C
Wexler, K
Muñoz, C
Conrad, B
Isganaitis, E
Estrada, S
Dreimane, D
McKnight-Menci, H
Ievers-Landis, C
Gunn, S
Carchidi, C
Pring, J
Seidman, D
Fisher, L
Ortiz, R
Barraza, V
Hannon, T
Yasuda, P
Carcelen, E
Ng, D
Haymond, M
Leibel, N
Law, E
Foster, S
Miranda, N
Casey, T
Kaplan, J
Boyd, S
Johnson, B
McKay, S
Bush, C
Cochenour, S
Guerra, N
Porter, K
Dahms, W
Bohl, C
Higgins, L
Guzman, V
Hernandez, S
Geffner, M
Berkowitz, R
Keady, J
Kutney, K
Malloy, M
Holden, H
Arslanian, S
Miller, D
Kriska, A
Thamotharan, S
Jeha, G
Levitt Katz, L
Quach, J
Farrell, R
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Copyright Copyright © 2021 Massachusetts Medical Society. All rights reserved.
Copyright © 2021 Massachusetts Medical Society.
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DOI 10.1056/NEJMoa2100165
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Snippet A clinical trial assessed the efficacy of three treatments, all involving metformin, on glycemic control in youth-onset type 2 diabetes. This follow-up study...
The prevalence of type 2 diabetes in youth is increasing, but little is known regarding the occurrence of related complications as these youths transition to...
AbstractBackgroundThe prevalence of type 2 diabetes in youth is increasing, but little is known regarding the occurrence of related complications as these...
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SubjectTerms Adolescence
Adolescent
Adolescent Medicine
Adverse events
Age
Algorithms
Antidiabetics
Blood pressure
Cardiology
Cardiology General
Child
Childhood Diseases
Chronic Kidney Disease
Clinical trials
Diabetes
Diabetes Complications - epidemiology
Diabetes Complications - ethnology
Diabetes mellitus (non-insulin dependent)
Diabetes Mellitus, Type 2 - complications
Diabetes Mellitus, Type 2 - drug therapy
Diabetic neuropathy
Diabetic retinopathy
Dyslipidemia
Dyslipidemias - complications
Dyslipidemias - epidemiology
Endocrinology
Eye diseases
Fasting
Female
Follow-Up Studies
Growth and Development
Humans
Hyperglycemia
Hypertension
Hypertension - complications
Hypertension - epidemiology
Hypoglycemic Agents - therapeutic use
Insulin
Insulin resistance
Kidney diseases
Laboratories
Lipids
Male
Metabolic disorders
Metformin
Metformin - therapeutic use
Microvasculature
Minority & ethnic groups
Nephrology
Ophthalmology
Ophthalmology General
Pediatrics
Pediatrics General
Retina
Risk Factors
Rosiglitazone
Teenagers
SubjectTermsDisplay Adolescent Medicine
Cardiology
Cardiology General
Childhood Diseases
Chronic Kidney Disease
Diabetes
Endocrinology
Growth and Development
Nephrology
Ophthalmology
Ophthalmology General
Pediatrics
Pediatrics General
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Title Long-Term Complications in Youth-Onset Type 2 Diabetes
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