Body mass index in adolescence, risk of type 2 diabetes and associated complications: A nationwide cohort study of men

Andreasson, Karin; Edqvist, Jon; Adiels, Martin; Björck, Lena; Lindgren, Martin; Sattar, Naveed; Lind, Marcus; Åberg, Maria; Rosengren, A

doi:10.1016/j.eclinm.2022.101356

Cited by 24 publications

(14 citation statements)

References 29 publications

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“…While, the predictivity increased to (AUC = 0.83) for the European cohort [ 38 ] and for QBB cohort (AUC = 0.83) when age, sex and BMI were included in the model but this was mostly driven by age differences between cases and controls in our cohort. The high performance observed following inclusion of covariates is reported by several studies, demonstrating the association of BMI and age with increasing T2D risk [ 56 , 57 ]. Moreover, studies have also shown that disease prediction in diabetes and cancer is enhanced using multiethnic based PGS panels [ 58 – 60 ].…”

Section: Discussionmentioning

confidence: 88%

Genome-wide association study and trans-ethnic meta-analysis identify novel susceptibility loci for type 2 diabetes mellitus

Elashi,

Toor,

Umlai

et al. 2024

BMC Med Genomics

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Background The genetic basis of type 2 diabetes (T2D) is under-investigated in the Middle East, despite the rapidly growing disease prevalence. We aimed to define the genetic determinants of T2D in Qatar. Methods Using whole genome sequencing of 11,436 participants (2765 T2D cases and 8671 controls) from the population-based Qatar Biobank (QBB), we conducted a genome-wide association study (GWAS) of T2D with and without body mass index (BMI) adjustment. Results We replicated 93 known T2D-associated loci in a BMI-unadjusted model, while 96 known loci were replicated in a BMI-adjusted model. The effect sizes and allele frequencies of replicated SNPs in the Qatari population generally concurred with those from European populations. We identified a locus specific to our cohort located between the APOBEC3H and CBX7 genes in the BMI-unadjusted model. Also, we performed a transethnic meta-analysis of our cohort with a previous GWAS on T2D in multi-ancestry individuals (180,834 T2D cases and 1,159,055 controls). One locus in DYNC2H1 gene reached genome-wide significance in the meta-analysis. Assessing polygenic risk scores derived from European- and multi-ancestries in the Qatari population showed higher predictive performance of the multi-ancestry panel compared to the European panel. Conclusion Our study provides new insights into the genetic architecture of T2D in a Middle Eastern population and identifies genes that may be explored further for their involvement in T2D pathogenesis.

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Section: Discussionmentioning

confidence: 88%

Genome-wide association study and trans-ethnic meta-analysis identify novel susceptibility loci for type 2 diabetes mellitus

Elashi,

Toor,

Umlai

et al. 2024

BMC Med Genomics

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“…23 Obesity is one of the predominant factors in the development of T2D [24][25][26] , and the linear increase in new onset T2D with increased BMI reported in this study is well described in the literature. 27 It is important to emphasize that only pre-operative BMI was included in the adjustments as postsurgery BMI information was not available and accordingly, weight trajectories after surgery could not be included in the analyses. It's still unknown how body weight and body composition changes after different types of CRC resection, and thus it is not clear whether changes in weight in any groups play a role in diabetes development.…”

Section: Discussionmentioning

confidence: 99%

The impact of colectomy and chemotherapy on risk of type 2 diabetes onset in patients with colorectal cancer: Nationwide cohort study in Denmark

Krag

Svane

Madsbad

et al. 2023

Preprint

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Background Comorbidity with type 2 diabetes (T2D) results in worsening of cancer-specific and overall prognosis in colorectal cancer (CRC) patients. The treatment of CRC per se may be diabetogenic. We aimed at assessing the impact of different types of surgical cancer resections as well as oncological treatment on risk of new-onset T2D in CRC patients. Method We developed a population-based cohort study including all Danish CRC patients, who had undergone CRC surgery between 2001-2018. Using nationwide register data, we identified and followed patients from date of surgery and until new-onset of T2D, death or end of follow-up. Results In total, 46,373 CRC patients were included and divided into six groups according to type of surgical resection: 10,566 Right-No-Chemo (23%), 4,645 Right-Chemo (10%), 10,151 Left-No-Chemo (22%), 5,257 Left-Chemo (11%), 9,618 Rectal-No-Chemo (21%) and 6,136 Rectal-Chemo (13%). During 245,466 person-years of follow-up 2,556 patients developed T2D. The incidence rate (IR) of T2D was highest in the Left-Chemo group 11.3 (95%CI: 10.4-12.2) per 1,000 person-years and lowest in the Rectal-No-Chemo group 9.6 (95%CI: 8.8-10.4). Between-group unadjusted hazard ratio (HR) of developing T2D was similar and non-significant. In the adjusted analysis, Rectal-No-Chemo was associated with lower risk of T2D (HR 0.86 [95%CI 0.75-0.98]) compared to Right-No-Chemo. For all six groups, an increased level of BMI resulted in a nearly twofold increased risk of developing T2D Conclusion This study suggests postoperative T2D screening should be prioritized in CRC survivors with overweight/obesity regardless of type of colorectal cancer treatment applied. Funding The Novo Nordisk Foundation (NNF17SA0031406); TrygFonden (101390; 20045; 125132).

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“…Despite the lack of concrete evidence, the pro-inflammatory milieu that characterizes central obesity could be blamed, at least in part, for the rapid progression of T2D in adolescents and young adults compared to later-onset T2D. Indeed, obesity is a more common feature of early-onset T2D with studies reporting that >80% of youth with T2D are obese at presentation compared with 50% of adults with the disease [229,230].…”

Section: Role Of Islet Inflammationmentioning

confidence: 99%

Beta Cell Dysfunction in Youth- and Adult-Onset Type 2 Diabetes: An Extensive Narrative Review with a Special Focus on the Role of Nutrients

et al. 2023

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Traditionally a disease of adults, type 2 diabetes (T2D) has been increasingly diagnosed in youth, particularly among adolescents and young adults of minority ethnic groups. Especially, during the recent COVID-19 pandemic, obesity and prediabetes have surged not only in minority ethnic groups but also in the general population, further raising T2D risk. Regarding its pathogenesis, a gradually increasing insulin resistance due to central adiposity combined with a progressively defective β-cell function are the main culprits. Especially in youth-onset T2D, a rapid β-cell activity decline has been observed, leading to higher treatment failure rates, and early complications. In addition, it is well established that both the quantity and quality of food ingested by individuals play a key role in T2D pathogenesis. A chronic imbalance between caloric intake and expenditure together with impaired micronutrient intake can lead to obesity and insulin resistance on one hand, and β-cell failure and defective insulin production on the other. This review summarizes our evolving understanding of the pathophysiological mechanisms involved in defective insulin secretion by the pancreatic islets in youth- and adult-onset T2D and, further, of the role various micronutrients play in these pathomechanisms. This knowledge is essential if we are to curtail the serious long-term complications of T2D both in pediatric and adult populations.

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Body mass index in adolescence, risk of type 2 diabetes and associated complications: A nationwide cohort study of men

Cited by 24 publications

References 29 publications

Genome-wide association study and trans-ethnic meta-analysis identify novel susceptibility loci for type 2 diabetes mellitus

Genome-wide association study and trans-ethnic meta-analysis identify novel susceptibility loci for type 2 diabetes mellitus

The impact of colectomy and chemotherapy on risk of type 2 diabetes onset in patients with colorectal cancer: Nationwide cohort study in Denmark

Beta Cell Dysfunction in Youth- and Adult-Onset Type 2 Diabetes: An Extensive Narrative Review with a Special Focus on the Role of Nutrients

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