Metabolic Contrasts Between Youth and Adults With Impaired Glucose Tolerance or Recently Diagnosed Type 2 Diabetes: II. Observations Using the Oral Glucose Tolerance Test

Ehrmann, David A.; Temple, Karla A.; Rue, Abby; Barengolts, Elena; Mokhlesi, Babak; Cauter, Eve Van; Sam, Susan; Miller, Marsha; Kahn, Steven E.; Atkinson, Karen M.; Palmer, Jerry P.; Utzschneider, Kristina M.; Gebremedhin, Tsige; Kernan-Schloss, Abigail; Kozedub, Alexandra; Montgomery, Brenda; Morse, Emily J.; Mather, Kieren J.; Garrett, Tammy; Hannon, Tamara S.; Lteif, Amale; Patel, Aniket; Chisholm, Robin; Moore, Karen; Pirics, Vivian; Pratt, Linda; Nadeau, Kristen J.; Gross, Susan; Zeitler, Philip; Williams, Jayne; Cree-Green, Melanie; Reyes, Yesenia Garcia; Vissat, Krista; Arslanian, Silva; Brown, Kathleen; Guerra, Nancy; Porter, Kristin E.; Caprio, Sonia; Savoye, Mary; Pierpont, Bridget; Buchanan, Thomas A.; Xiang, Anny H.; Trigo, Enrique; Beale, Elizabeth; Hendee, Fadi; Katkhouda, Namir; Nayak, Krishan; Martinez, Mayra P.; Montgomery, Cortney; Wang, Xinhui; Edelstein, Sharon L.; Lachin, John M.; Hogan, Ashley N.; Marcovina, Santica M.; Harting, Jessica; Albers, John J.; Hill, Dave; Savage, Peter J.; Leschek, Ellen

doi:10.2337/dc18-0243

Cited by 94 publications

(37 citation statements)

References 38 publications

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“…By the end of the study, girls had restored insulin sensitivity and normalised insulin secretion, whereas boys had persistently increased insulin resistance and exhibited a decline in beta cell reserve and increased fasting glucose levels [67]. Loss of glucose-stimulated insulin secretion was also observed in the youth type 2 diabetes cohort in the National Institute of Health (NIH) Restoring Insulin Secretion (RISE) study (no sex differences have been reported to date in the 91 participants) [68]. Thus, obesity, insulin resistance and insulin hypersecretion [61] are likely to be key mediators of type 2 diabetes in youth.…”

Section: Mechanism Of Type 2 Diabetes Onset In Youthmentioning

confidence: 90%

Sex differences in the burden of type 2 diabetes and cardiovascular risk across the life course

et al. 2019

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By 2017 estimates, diabetes mellitus affects 425 million people globally; approximately 90-95% of these have type 2 diabetes. This narrative review highlights two domains of sex differences related to the burden of type 2 diabetes across the life span: sex differences in the prevalence and incidence of type 2 diabetes, and sex differences in the cardiovascular burden conferred by type 2 diabetes. In the presence of type 2 diabetes, the difference in the absolute rates of cardiovascular disease (CVD) between men and women lessens, albeit remaining higher in men. Large-scale observational studies suggest that type 2 diabetes confers 25-50% greater excess risk of incident CVD in women compared with men. Physiological and behavioural mechanisms that may underpin both the observed sex differences in the prevalence of type 2 diabetes and the associated cardiovascular burden are discussed in this review. Gender differences in social behavioural norms and disparities in provider-level treatment patterns are also highlighted, but not described in detail. We conclude by discussing research gaps in this area that are worthy of further investigation.

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Section: Mechanism Of Type 2 Diabetes Onset In Youthmentioning

confidence: 90%

Sex differences in the burden of type 2 diabetes and cardiovascular risk across the life course

et al. 2019

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“…The Restoring Insulin Secretion (RISE) Study has, for the first time, directly compared insulin sensitivity, beta cell function and treatment response in adults and youths with IGT or recently diagnosed type 2 diabetes [98][99][100]. At baseline, youths were more insulin resistant and had greater insulin responses for any degree of insulin sensitivity despite similar levels of obesity and dysglycaemia as compared with adults [98,99]. Further, in youths with IGT and type 2 diabetes, beta cell function progressively deteriorated while on metformin alone or insulin glargine followed by metformin [100]; this deterioration was not observed in adults.…”

Section: Youths Vs Adults: New Insights Into the Pathophysiology Of Dmentioning

confidence: 99%

Early beta cell dysfunction vs insulin hypersecretion as the primary event in the pathogenesis of dysglycaemia

2020

Self Cite

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Obesity and insulin resistance are associated with the development of type 2 diabetes. It is well accepted that beta cell dysfunction is required for hyperglycaemia to occur. The prevailing view is that, in the presence of insulin resistance, beta cell dysfunction that occurs early in the course of the disease process is the critical abnormality. An alternative model has been proposed in which primary beta cell overstimulation results in insulin hypersecretion that then leads to the development of obesity and insulin resistance, and ultimately to beta cell exhaustion. In this review, data from preclinical and clinical studies, including intervention studies, are discussed in the context of these models. The preponderance of the data supports the view that an early beta cell functional defect is the more likely mechanism underlying the pathogenesis of hyperglycaemia in the majority of individuals who develop type 2 diabetes.

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“…At the same time, the unabated increase in childhood obesity is also tightly linked to the emergence of T2D as a new type of pediatric diabetes [92]. Early results from the RISE study show the clinical course is markedly different in adolescents compared to adults suggesting the need for further research to better prevent and manage this unique and increasingly important population [93][94][95][96].…”

Section: Areas For Future Researchmentioning

confidence: 99%

The Continuing Evolution of Precision Health in Type 2 Diabetes: Achievements and Challenges

Lin

Wessel

2019

Curr Diab Rep

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Purpose of Review The purpose of this review was to summarize recent advances in the genomics of type 2 diabetes (T2D) and to highlight current initiatives to advance precision health. Recent Findings Generation of multi-omic data to measure each of the 'biologic layers', developments in describing genomic function and annotation in T2D relevant tissue, along with the increasing recognition that T2D is a heterogeneous disease, and large-scale collaborations have all contributed to advancing our understanding of the molecular basis of T2D. Summary Substantial advances have been made in understanding the molecular basis of T2D pathogenesis, such that precision health diabetes is increasingly becoming a reality. For precision diabetes to become routine in clinical and public health, additional large-scale multiomic initiatives are needed along with better assessment of our environment to delineate an individual's diabetes subtype for improved detection and management.

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Metabolic Contrasts Between Youth and Adults With Impaired Glucose Tolerance or Recently Diagnosed Type 2 Diabetes: II. Observations Using the Oral Glucose Tolerance Test

Cited by 94 publications

References 38 publications

Sex differences in the burden of type 2 diabetes and cardiovascular risk across the life course

Sex differences in the burden of type 2 diabetes and cardiovascular risk across the life course

Early beta cell dysfunction vs insulin hypersecretion as the primary event in the pathogenesis of dysglycaemia

The Continuing Evolution of Precision Health in Type 2 Diabetes: Achievements and Challenges

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