Relationship Between Insulin Resistance and β-Cell Dysfunction in Subphenotypes of Prediabetes and Type 2 Diabetes

Færch, Kristine; Johansen, Nanna Borup; Witte, Daniel R.; Lauritzen, Torsten; Vistisen, Dorte

doi:10.1210/jc.2014-2853

Cited by 46 publications

(34 citation statements)

References 37 publications

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“…In total, 755 individuals were included. The participants in this study are thus a subpopulation of the participants in previously published studies [4,22].…”

Section: Methodsmentioning

confidence: 99%

“…DI is an expression of the ability of the beta cells to compensate for decreased insulin sensitivity [21]. DI was calculated by multiplying BIGTT-AIR with ISI 0,120 [4].…”

Section: Methodsmentioning

confidence: 99%

“…Initially, the pancreatic beta cells compensate for decreased insulin sensitivity by secreting more insulin, but with time the compensatory mechanism fails and hyperglycaemia ensues [1,2]. It is still not clear whether decreased sensitivity to insulin or decreased insulin production is the primary defect in type 2 diabetes [3,4]. Furthermore, several pathogenic processes may arise through genetic, epigenetic and environmental influences, e.g.…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, several pathogenic processes may arise through genetic, epigenetic and environmental influences, e.g. physical inactivity, leading to substantial heterogeneity in the aetiology and pathogenesis of type 2 diabetes [1][2][3][4]. Before type 2 diabetes is diagnosed, glucose levels are slightly increased in the prediabetes period [5].…”

Section: Introductionmentioning

confidence: 99%

“…Prediabetes is defined as isolated impaired fasting glycaemia (i-IFG), isolated impaired glucose tolerance (i-IGT), or combined fasting and post-challenge hyperglycaemia (IFG + IGT). Reduced peripheral insulin sensitivity and progressive loss of beta cell function are the pathophysiological attributes of individuals with i-IGT [4,[6][7][8], whereas hepatic insulin resistance, increased endogenous glucose production and reduced first-phase insulin release characterise individuals with i-IFG [6][7][8]. Combinations of peripheral and hepatic insulin resistance and beta cell dysfunction characterise individuals with IFG + IGT.…”

Section: Introductionmentioning

confidence: 99%

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Physical activity energy expenditure vs cardiorespiratory fitness level in impaired glucose metabolism

et al. 2015

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Aim/hypothesis Little is known about the relative roles of physical activity energy expenditure (PAEE) and cardiorespiratory fitness (CRF) as determinants of glucose regulation. The aim of this study was to examine the associations of PAEE and CRF with markers of glucose metabolism, and to test the hypothesis that CRF modifies the association between PAEE and glucose metabolism. Methods We analysed cross-sectional data from 755 adults from the Danish ADDITION-PRO study. On the basis of OGTT results, participants without known diabetes were classified as having normal glucose tolerance, isolated impaired fasting glycaemia (i-IFG), isolated impaired glucose tolerance (i-IGT), combined IFG + IGT or screen-detected diabetes mellitus. Markers of insulin sensitivity and beta cell function were determined. PAEE was measured using a combined heart rate and movement sensor. CRF (maximal oxygen uptake) was estimated using a submaximal 8 min step test. The associations were examined by linear regression analysis. Results were adjusted for relevant confounders. Results PAEE and CRF were reduced in individuals with i-IGT, combined IFG + IGT and screen-detected diabetes mellitus, but were not significantly different in individuals with i-IFG compared with those with normal glucose tolerance. When adjusting CRF for PAEE and vice versa, PAEE and CRF were both associated with lower fasting and 2 h insulin and higher peripheral insulin sensitivity. CRF was additionally associated with lower fasting and 2 h glucose and higher insulin sensitivity and beta cell function. There was no interaction between CRF and PAEE for any markers of glucose metabolism. Conclusions/interpretation Only CRF, not PAEE, appears to be independently associated with plasma glucose levels and beta cell function, suggesting that CRF may be particularly important for glycaemic control.

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“…In total, 755 individuals were included. The participants in this study are thus a subpopulation of the participants in previously published studies [4,22].…”

Section: Methodsmentioning

confidence: 99%

“…DI is an expression of the ability of the beta cells to compensate for decreased insulin sensitivity [21]. DI was calculated by multiplying BIGTT-AIR with ISI 0,120 [4].…”

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Physical activity energy expenditure vs cardiorespiratory fitness level in impaired glucose metabolism

et al. 2015

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Diagnosis and Management of Prediabetes

Echouffo‐Tcheugui¹,

Perreault

et al. 2023

JAMA

122

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ImportancePrediabetes, an intermediate stage between normal glucose regulation and diabetes, affects 1 in 3 adults in the US and approximately 720 million individuals worldwide.ObservationsPrediabetes is defined by a fasting glucose level of 100 to 125 mg/dL, a glucose level of 140 to 199 mg/dL measured 2 hours after a 75-g oral glucose load, or glycated hemoglobin level (HbA1C) of 5.7% to 6.4% or 6.0% to 6.4%. In the US, approximately 10% of people with prediabetes progress to having diabetes each year. A meta-analysis found that prediabetes at baseline was associated with increased mortality and increased cardiovascular event rates (excess absolute risk, 7.36 per 10 000 person-years for mortality and 8.75 per 10 000 person-years for cardiovascular disease during 6.6 years). Intensive lifestyle modification, consisting of calorie restriction, increased physical activity (≥150 min/wk), self-monitoring, and motivational support, decreased the incidence of diabetes by 6.2 cases per 100 person-years during a 3-year period. Metformin decreased the risk of diabetes among individuals with prediabetes by 3.2 cases per 100 person-years during 3 years. Metformin is most effective for women with prior gestational diabetes and for individuals younger than 60 years with body mass index of 35 or greater, fasting plasma glucose level of 110 mg/dL or higher, or HbA1c level of 6.0% or higher.Conclusions and RelevancePrediabetes is associated with increased risk of diabetes, cardiovascular events, and mortality. First-line therapy for prediabetes is lifestyle modification that includes weight loss and exercise or metformin. Lifestyle modification is associated with a larger benefit than metformin.

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Prevalence of Prediabetes Among Adolescents and Young Adults in the United States, 2005-2016

et al. 2020

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IMPORTANCE Individuals with prediabetes are at increased risk of developing type 2 diabetes, chronic kidney disease, and cardiovascular disease. The incidence and prevalence of type 2 diabetes in the US adolescent population have increased in the last decade. Therefore, it is important to monitor the prevalence of prediabetes and varying levels of glucose tolerance to assess the future risk of type 2 diabetes in the youngest segment of the population.OBJECTIVE To examine the prevalence of impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and increased glycated hemoglobin A 1c (HbA 1c ) levels in US adolescents (aged 12-18 years) and young adults (aged 19-34 years) without diabetes. DESIGN, SETTING, AND PARTICIPANTS This cross-sectional analyses of the 2005-2016 NationalHealth and Nutrition Examination Survey assessed a population-based sample of adolescents and young adults who were not pregnant, did not have diabetes, and had measured fasting plasma glucose, 2-hour plasma glucose after a 75-g oral glucose tolerance test, and HbA 1c levels. Analysis began in April 2017. MAIN OUTCOMES AND MEASURESImpaired fasting glucose was defined as fasting plasma glucose of 100 mg/dL to less than 126 mg/dL, IGT as 2-hour plasma glucose of 140 mg/dL to less than 200 mg/dL, and increased HbA 1c level as HbA 1c level between 5.7% and 6.4%. The prevalence of IFG, isolated IFG, IGT, isolated IGT, increased HbA 1c level, isolated increased HbA 1c level, and prediabetes (defined as having IFG, IGT, or increased HbA 1c level) were estimated. Fasting insulin levels and cardiometabolic risk factors across glycemic abnormality phenotypes were also compared. Obesity was defined as having age-and sex-specific body mass index (calculated as weight in kilograms divided by height in meters squared) in the 95th percentile or higher in adolescents or 30 or higher in young adults. RESULTSOf 5786 individuals, 2606 (45%) were adolescents and 3180 (55%) were young adults. Of adolescents, 50.6% (95% CI, 47.6%-53.6%) were boys, and 50.6% (95% CI, 48.8%-52.4%) of young adults were men. Among adolescents, the prevalence of prediabetes was 18.0% (95% CI, 16.0%-20.1%) and among young adults was 24.0% (95% CI, 22.0%-26.1%). Impaired fasting glucose constituted the largest proportion of prediabetes, with prevalence of 11.1% (95% CI, 9.5%-13.0%) in adolescents and 15.8% (95% CI, 14.0%-17.9%) in young adults. In multivariable logistic models including age, sex, race/ethnicity, and body mass index, the predictive marginal prevalence of prediabetes was significantly higher in male than in female individuals (22.5% [95% CI, 19.5%-25.4%] vs 13.4% [95% CI, 10.8%-16.5%] in adolescents and 29.1% [95% CI, 26.4%-32.1%] vs 18.8% [95% CI, 16.5%-21.3%] in young adults). Prediabetes prevalence was significantly higher in individuals with obesity than in those with normal weight (25.7% [95% CI, 20.0%-32.4%] vs 16.4% [95% CI, 14.3%-18.7%] in adolescents and 36.9% [95% CI, 32.9%-41.1%] vs 16.6% [95% CI, 14.2%-19.4%] in young adults). Compared with persons wi...

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Relationship Between Insulin Resistance and β-Cell Dysfunction in Subphenotypes of Prediabetes and Type 2 Diabetes

Cited by 46 publications

References 37 publications

Physical activity energy expenditure vs cardiorespiratory fitness level in impaired glucose metabolism

Physical activity energy expenditure vs cardiorespiratory fitness level in impaired glucose metabolism

Diagnosis and Management of Prediabetes

Prevalence of Prediabetes Among Adolescents and Young Adults in the United States, 2005-2016

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