Youth With Type 1 Diabetes Have Adipose, Hepatic, and Peripheral Insulin Resistance

Cree-Green, Melanie; Stuppy, Jacob J.; Thurston, Jessica; Bergman, Bryan C.; Coe, Gregory; Baumgartner, Amy; Bacon, Samantha; Scherzinger, Ann; Pyle, Laura; Nadeau, Kristen J.

doi:10.1210/jc.2018-00433

Cited by 46 publications

(51 citation statements)

References 35 publications

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“…This IR in T1DM occurs irrespective of obesity and metabolic syndrome features (58, 61–63). Moreover, IR confers higher risk for a more atherogenic lipoprotein profile (64, 65) and micro- and macrovascular complications in T1DM youth (66) and adults (67, 68).…”

Section: Introductionmentioning

confidence: 95%

Pathogenesis of Lipid Disorders in Insulin Resistance: a Brief Review

2018

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Purpose of the review: Insulin resistance (IR) is recognized to play an important role in the pathogenesis of dyslipidemia. This review summarizes the complex interplay between IR and dyslipidemia in people with and without diabetes. Recent findings: IR impacts the metabolism of triglycerides, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and very low-density lipoprotein cholesterol (VLDL-C) by several mechanisms. Trials with insulin sensitizing therapies, including biguanides and thiazolidinediones, have provided inconsistent results on lipid lowering in people with and without diabetes. In this review, we focus on the pathophysiological interplay between IR and dyslipidemia and recapitulate lipid and lipoprotein data from insulin sensitizing trials. Conclusion: Further research elucidating the reciprocal relationship between IR and dyslipidemia is needed to better target these important risk factors for cardiovascular disease.

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Section: Introductionmentioning

confidence: 95%

Pathogenesis of Lipid Disorders in Insulin Resistance: a Brief Review

2018

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“…Data from youth aged 12 to 21 years recruited from the RESistance to InSulin in Type 1 ANd Type 2 diabetes (RESISTANT) study and the Androgens and Insulin Resistance Study (AIRS) cohorts (studies performed prior to ClinicalTrials.gov identifier requirements) were used for this secondary data analysis. Inclusion criteria were BMI ≥ 95th percentile specific for sex and age for the group with obesity, BMI = 10th to 84th percentile for the normal‐weight participants in the control group, and sedentary status, to minimize impacts of varying physical activity on IS (< 3 hours of regular exercise per week, validated with both a 3‐day activity recall and 7 days of accelerometer use).…”

Section: Methodsmentioning

confidence: 99%

“…Informed consent was obtained from all participants ≥ 18 years of age, and parental consent and participant assent were obtained from all participants < 18 years of age. The two groups included in this secondary analysis were originally enrolled as the normal‐weight control group to match those with type 1 diabetes and lean PCOS participants and the control group with obesity to match those with PCOS and T2D participants with obesity. The comparison of the two different weight control groups has not been performed.…”

Section: Methodsmentioning

confidence: 99%

Muscle Insulin Resistance in Youth with Obesity and Normoglycemia is Associated with Altered Fat Metabolism

Cree‐Green

Wiromrat

Stuppy

et al. 2019

Obesity

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Objective This study aimed to phenotype and compare adipose, hepatic, and muscle insulin sensitivity (IS) in a diet‐ and physical activity–controlled cohort of normoglycemic youth with obesity with that of participants without obesity (controls) to distinguish early metabolic abnormalities in pediatric obesity. Methods Thirty‐eight participants (17 in the control group [BMI < 85th percentile] and 21 youth with obesity [BMI ≥ 95th percentile]; age: 12‐21 years; 76% female; Tanner stage 4‐5; sedentary) were enrolled. Tissue‐specific IS was measured using a four‐phase hyperinsulinemic‐euglycemic clamp with glucose and glycerol isotope tracers to assess suppression of endogenous glucose release and lipolysis by insulin. Intramyocellular lipid content was assessed by 1H–magnetic resonance spectroscopy, and hepatic fat fraction (HFF) and visceral fat were assessed by magnetic resonance imaging. Calf‐muscle mitochondrial activity was measured with exercise‐stimulated 31P–magnetic resonance spectroscopy. Results Youth with obesity had higher HFF (P < 0.001), visceral fat (P = 0.024), and intramyocellular lipid content (P = 0.017) and lower muscle (glucose clearance rate [P < 0.001]), adipose (P < 0.0001), and hepatic IS (P < 0.003). Mitochondria postexercise response was not different. In participants with obesity, muscle IS inversely correlated with HFF (r = 0.700, P = 0.002) and suppressed free fatty acid concentrations (r = −0.65, P = 0.003). Conclusions Inactive normoglycemic youth with obesity had decreased muscle, adipose, and hepatic IS. Free fatty acids and liver fat were inversely associated with muscle IS, which argues for lipid‐targeted interventions.

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“…Sustained obesity (cumulative excess BMI ≥5 kg/m 2 ) enhanced the risk for T1DM in pediatric and young women (<35 y-o) but the risk diminished with increasing age (Ferrara et al 2017). While insulin resistance in T1DM patients occurs regardless of accompanying obesity or metabolic syndrome (Cree-Green et al 2018), recent data indicate that a significant fraction (30%) of girls and adolescent females with T1DM are overweight or obese (Maffeis et al 2018), which may have bearing on ENDO risk. Table 1 provides a list of molecules independently implicated in ENDO and T1DM, based on studies with human patients and animal disease models.…”

Section: Predisposition and Body Mass Indexmentioning

confidence: 99%

Co-morbidity of type 1 diabetes and endometriosis: bringing a new paradigm into focus

Simmen

Brown

Quick

et al. 2019

Journal of Endocrinology

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Type 1 diabetes mellitus and endometriosis separately affect millions of women worldwide. Reproductive-age women diagnosed with type 1 diabetes may also suffer from endometriosis, but the asymptomatic pre-clinical period of highly variable duration for each condition can lead to challenges in the timely recognition of co-morbid disease onset and misdiagnosis. While knowledge of the pathogenesis of each condition has grown substantially, co-morbid endometriosis and type 1 diabetes has not been widely considered and much less addressed. This review discusses the molecular rationale for the likelihood of their co-existence, and prospects for improvements in therapeutic strategies and reduced complications, if this paradigm is included as a significant variable in disease management.

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Youth With Type 1 Diabetes Have Adipose, Hepatic, and Peripheral Insulin Resistance

Abstract: Adolescents with T1D have adipose, hepatic and peripheral IR. This IR occurs regardless of obesity and metabolic syndrome features. Youth with T1D may benefit from interventions directed at improving IR in these tissues, and this area requires further research.

Cited by 46 publications

References 35 publications

Pathogenesis of Lipid Disorders in Insulin Resistance: a Brief Review

Pathogenesis of Lipid Disorders in Insulin Resistance: a Brief Review

Muscle Insulin Resistance in Youth with Obesity and Normoglycemia is Associated with Altered Fat Metabolism

Co-morbidity of type 1 diabetes and endometriosis: bringing a new paradigm into focus

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