Role of obesity on all-cause mortality in whites with type 2 diabetes from Italy

R. Di Paola, A. Marucci, A. Fontana, C. Menzaghi, L. Salvemini, M. Copetti, F. Pellegrini, S. De Cosmo, V. Trischitta

Research output: Contribution to journalArticle

Abstract

Mortality rate of diabetic patients is twice as much that of non-diabetic individuals. The role of obesity on mortality risk in patients with type 2 diabetes is controversial. Aim of our study was to address the relationship between obesity and all-cause mortality in a real-life set of white patients with type 2 diabetes from central-southern Italy from the Gargano Mortality Study (GMS). In addition, we used genetic data from genome-wide association studies (GWAs)-derived single nucleotide polymorphisms (SNPs) firmly associated with body mass index (BMI), in order to investigate the intrinsic nature of reduced mortality rate we, in fact, observed in obese patients. Study subjects with type 2 diabetes (n = 764) are part of the GMS, which is aimed at unraveling predictors of incident all-cause mortality. Time-to-death analyses were performed by Cox regression. Association between genotype risk score and obesity was tested by logistic regression. Of the 32 SNPs firmly associated with BMI, we investigated those with BMI β value ≥0.10 kg/m2 and allele frequency ≥10 %. Genotyping was performed by KBioscience (http://www.lgcgenomics.com/). In GMS, obesity predicted a 45 % reduction in all-cause mortality. Individuals with high "obesity genetic load" (i.e., those carrying >9 risk alleles) were 60 % more likely to be obese as compared to individuals with low "obesity genetic load." Most importantly, mortality rate was not different in individuals with high and low "obesity genetic load," thus indicating no role of obesity genes on all-cause mortality and speaking against a cause-effect relationship underlying the association between obesity and reduced mortality rate.

Original languageEnglish
Pages (from-to)971-976
Number of pages6
JournalActa Diabetologica
Volume50
Issue number6
DOIs
Publication statusPublished - Dec 2013

Fingerprint

Type 2 Diabetes Mellitus
Italy
Obesity
Mortality
Genetic Load
Body Mass Index
Single Nucleotide Polymorphism
Genome-Wide Association Study
Gene Frequency
Logistic Models
Alleles
Genotype

Keywords

  • Mendelian randomization
  • Mortality prediction
  • Paradoxical effect
  • Reverse epidemiology

ASJC Scopus subject areas

  • Endocrinology
  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Role of obesity on all-cause mortality in whites with type 2 diabetes from Italy. / Di Paola, R.; Marucci, A.; Fontana, A.; Menzaghi, C.; Salvemini, L.; Copetti, M.; Pellegrini, F.; De Cosmo, S.; Trischitta, V.

In: Acta Diabetologica, Vol. 50, No. 6, 12.2013, p. 971-976.

Research output: Contribution to journalArticle

@article{dd7972ee09a1409fb14ac0c33c6c5739,
title = "Role of obesity on all-cause mortality in whites with type 2 diabetes from Italy",
abstract = "Mortality rate of diabetic patients is twice as much that of non-diabetic individuals. The role of obesity on mortality risk in patients with type 2 diabetes is controversial. Aim of our study was to address the relationship between obesity and all-cause mortality in a real-life set of white patients with type 2 diabetes from central-southern Italy from the Gargano Mortality Study (GMS). In addition, we used genetic data from genome-wide association studies (GWAs)-derived single nucleotide polymorphisms (SNPs) firmly associated with body mass index (BMI), in order to investigate the intrinsic nature of reduced mortality rate we, in fact, observed in obese patients. Study subjects with type 2 diabetes (n = 764) are part of the GMS, which is aimed at unraveling predictors of incident all-cause mortality. Time-to-death analyses were performed by Cox regression. Association between genotype risk score and obesity was tested by logistic regression. Of the 32 SNPs firmly associated with BMI, we investigated those with BMI β value ≥0.10 kg/m2 and allele frequency ≥10 {\%}. Genotyping was performed by KBioscience (http://www.lgcgenomics.com/). In GMS, obesity predicted a 45 {\%} reduction in all-cause mortality. Individuals with high {"}obesity genetic load{"} (i.e., those carrying >9 risk alleles) were 60 {\%} more likely to be obese as compared to individuals with low {"}obesity genetic load.{"} Most importantly, mortality rate was not different in individuals with high and low {"}obesity genetic load,{"} thus indicating no role of obesity genes on all-cause mortality and speaking against a cause-effect relationship underlying the association between obesity and reduced mortality rate.",
keywords = "Mendelian randomization, Mortality prediction, Paradoxical effect, Reverse epidemiology",
author = "{Di Paola}, R. and A. Marucci and A. Fontana and C. Menzaghi and L. Salvemini and M. Copetti and F. Pellegrini and {De Cosmo}, S. and V. Trischitta",
year = "2013",
month = "12",
doi = "10.1007/s00592-013-0509-3",
language = "English",
volume = "50",
pages = "971--976",
journal = "Acta Diabetologica",
issn = "0940-5429",
publisher = "Springer-Verlag Italia s.r.l.",
number = "6",

}

TY - JOUR

T1 - Role of obesity on all-cause mortality in whites with type 2 diabetes from Italy

AU - Di Paola, R.

AU - Marucci, A.

AU - Fontana, A.

AU - Menzaghi, C.

AU - Salvemini, L.

AU - Copetti, M.

AU - Pellegrini, F.

AU - De Cosmo, S.

AU - Trischitta, V.

PY - 2013/12

Y1 - 2013/12

N2 - Mortality rate of diabetic patients is twice as much that of non-diabetic individuals. The role of obesity on mortality risk in patients with type 2 diabetes is controversial. Aim of our study was to address the relationship between obesity and all-cause mortality in a real-life set of white patients with type 2 diabetes from central-southern Italy from the Gargano Mortality Study (GMS). In addition, we used genetic data from genome-wide association studies (GWAs)-derived single nucleotide polymorphisms (SNPs) firmly associated with body mass index (BMI), in order to investigate the intrinsic nature of reduced mortality rate we, in fact, observed in obese patients. Study subjects with type 2 diabetes (n = 764) are part of the GMS, which is aimed at unraveling predictors of incident all-cause mortality. Time-to-death analyses were performed by Cox regression. Association between genotype risk score and obesity was tested by logistic regression. Of the 32 SNPs firmly associated with BMI, we investigated those with BMI β value ≥0.10 kg/m2 and allele frequency ≥10 %. Genotyping was performed by KBioscience (http://www.lgcgenomics.com/). In GMS, obesity predicted a 45 % reduction in all-cause mortality. Individuals with high "obesity genetic load" (i.e., those carrying >9 risk alleles) were 60 % more likely to be obese as compared to individuals with low "obesity genetic load." Most importantly, mortality rate was not different in individuals with high and low "obesity genetic load," thus indicating no role of obesity genes on all-cause mortality and speaking against a cause-effect relationship underlying the association between obesity and reduced mortality rate.

AB - Mortality rate of diabetic patients is twice as much that of non-diabetic individuals. The role of obesity on mortality risk in patients with type 2 diabetes is controversial. Aim of our study was to address the relationship between obesity and all-cause mortality in a real-life set of white patients with type 2 diabetes from central-southern Italy from the Gargano Mortality Study (GMS). In addition, we used genetic data from genome-wide association studies (GWAs)-derived single nucleotide polymorphisms (SNPs) firmly associated with body mass index (BMI), in order to investigate the intrinsic nature of reduced mortality rate we, in fact, observed in obese patients. Study subjects with type 2 diabetes (n = 764) are part of the GMS, which is aimed at unraveling predictors of incident all-cause mortality. Time-to-death analyses were performed by Cox regression. Association between genotype risk score and obesity was tested by logistic regression. Of the 32 SNPs firmly associated with BMI, we investigated those with BMI β value ≥0.10 kg/m2 and allele frequency ≥10 %. Genotyping was performed by KBioscience (http://www.lgcgenomics.com/). In GMS, obesity predicted a 45 % reduction in all-cause mortality. Individuals with high "obesity genetic load" (i.e., those carrying >9 risk alleles) were 60 % more likely to be obese as compared to individuals with low "obesity genetic load." Most importantly, mortality rate was not different in individuals with high and low "obesity genetic load," thus indicating no role of obesity genes on all-cause mortality and speaking against a cause-effect relationship underlying the association between obesity and reduced mortality rate.

KW - Mendelian randomization

KW - Mortality prediction

KW - Paradoxical effect

KW - Reverse epidemiology

UR - http://www.scopus.com/inward/record.url?scp=84890548210&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84890548210&partnerID=8YFLogxK

U2 - 10.1007/s00592-013-0509-3

DO - 10.1007/s00592-013-0509-3

M3 - Article

C2 - 23959063

AN - SCOPUS:84890548210

VL - 50

SP - 971

EP - 976

JO - Acta Diabetologica

JF - Acta Diabetologica

SN - 0940-5429

IS - 6

ER -