Adipose Tissue Insulin Resistance in Youth on the Spectrum From Normal Weight to Obese and From Normal Glucose Tolerance to Impaired Glucose Tolerance to Type 2 Diabetes

Kim, Joon Young; Bacha, Fida; Tfayli, Hala; Michaliszyn, Sara F.; Yousuf, Shahwar; Arslanian, Silva

doi:10.2337/dc18-1178

Cited by 89 publications

(79 citation statements)

References 39 publications

(55 reference statements)

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“…Increasing adiponectin expression reduces metabolic abnormalities associated with obesity and T2D. Our data are in agreement with a previous report (48) that ADP concentrations are reduced in prediabetes and T2D. Our data are also consistent with the findings that ADP knockout mice have decreased mitochondrial content in skeletal muscle associated with insulin resistance and mitochondrial dysfunctional skeletal muscle (49): and that adiponectin may affect mitochondrial biogenesis (30).…”

Section: Discussionsupporting

confidence: 93%

Mitochondrial-Derived Peptides Are Down Regulated in Diabetes Subjects

et al. 2019

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Background: Mitochondrial dysfunction is implicated in the pathogenesis of Type 2 diabetes (T2D) and the development of diabetes related complications such as cardiovascular disease and stroke. Mitochondria produce several small polypeptides that may influence mitochondrial function and may impact on insulin sensitivity, such as humanin (HN) and the mitochondrial open reading frame of the 12S rRNA type-c (MOTS-c) that are mitochondrial derived proteins (MDP). The aim of this study was to determine MDP in normal, prediabetes and diabetes subjects. Subjects and Measurements: In this cross-sectional study, we analyzed the serum concentrations of MDP and adiponectin (ADP) in 225 subjects: normal ( n = 68), pre-diabetes ( n = 33), T2D less than (good control; n = 31), and greater than HbA1c 7% (poor control; n = 93) subjects. The relationship of serum MDP and ADP concentrations with biochemical and anthropometric measurements were performed and assessed by multilinear regression. Results: Serum HN concentrations were lower in T2D ( p < 0.0001) and negatively correlated with age ( p < 0.0001), HbA1c ( p < 0.0001), glucose ( p < 0.0001), triglycerides ( p < 0.003), ALT ( p < 0.004), and TG/HDL ratio ( p < 0.001). Circulating HN levels were positively correlated to cholesterol ( p < 0.017), LDL ( p < 0.001), and HDL ( p < 0.001). Linear regression analysis showed that HbA1c and ALT were two independent predictors of circulating HN. Similarly, serum MOTS-c was significantly lower in T2D subjects compared to controls ( p < 0.007). Circulating MOTS-c positively correlated with BMI ( p < 0.035), total cholesterol ( p < 0.0001), and LDL ( p < 0.001) and negatively correlated with age ( p < 0.002), HbA1c ( p < 0.001), and glucose ( p < 0.002). Serum ADP concentrations were lower in T2D ( p < 0.002) and negatively correlated with HbA1c ( p < 0.001), weight ( p < 0.032) TG ( p < 0.0001), and ALT ( p < 0.0001); and positively correlated with HDL ( p < 0.0001) and HN ( p < 0.003). Linear regression analysis showed that HbA1c and weight were two independent predictors of circulating ADP. Multilinear regression showed that HN and MOT-c correlated with each other, and only HN correlated with HbA1c. Conclusion: The MDPs HN and MOT-c, similar to ADP, are decreased in T2D and correlate with HbA1c. The data provide a...

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Section: Discussionsupporting

confidence: 93%

Mitochondrial-Derived Peptides Are Down Regulated in Diabetes Subjects

et al. 2019

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“…The chronic inflammation in the adipose tissue or liver, mainly during obesity, has been linked to insulin sensitivity [153]. Furthermore, adipose tissue insulin resistance is one of the pathophysiological components of type 2 diabetes [154]. On the contrary, correlation of Cdc42 and IR in some tissues (such as skeleton muscles and neuron cells) remains unclear and shows significant variety in our review [86,87].…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

Cdc42: A Novel Regulator of Insulin Secretion and Diabetes-Associated Diseases

Huang

Lai

Qian

et al. 2019

IJMS

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Cdc42, a member of the Rho GTPases family, is involved in the regulation of several cellular functions including cell cycle progression, survival, transcription, actin cytoskeleton organization and membrane trafficking. Diabetes is a chronic and metabolic disease, characterized as glycometabolism disorder induced by insulin deficiency related to β cell dysfunction and peripheral insulin resistance (IR). Diabetes could cause many complications including diabetic nephropathy (DN), diabetic retinopathy and diabetic foot. Furthermore, hyperglycemia can promote tumor progression and increase the risk of malignant cancers. In this review, we summarized the regulation of Cdc42 in insulin secretion and diabetes-associated diseases. Organized researches indicate that Cdc42 is a crucial member during the progression of diabetes, and Cdc42 not only participates in the process of insulin synthesis but also regulates the insulin granule mobilization and cell membrane exocytosis via activating a series of downstream factors. Besides, several studies have demonstrated Cdc42 as participating in the pathogenesis of IR and DN and even contributing to promote cancer cell proliferation, survival, invasion, migration, and metastasis under hyperglycemia. Through the current review, we hope to cast light on the mechanism of Cdc42 in diabetes and associated diseases and provide new ideas for clinical diagnosis, treatment, and prevention.

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“…[10][11][12][13][14][15][16] However, most studies which employed AT-IR investigated people with obesity and/or type 2 diabetes and were conducted in Western countries. [10][11][12][13][14][15][16] We, therefore, investigated determinants, correlates and usefulness of AT-IR in Japanese women without diabetes and obesity, populations in which confounding factors are so scarce. 17 Because we have shown that endurance training lowered AT-IR in young women, 18 we excluded female collegiate athletes in the present study.…”

mentioning

confidence: 99%

Determinants and correlates of adipose tissue insulin resistance index in Japanese women without diabetes and obesity

Kitaoka

Tsuboi

Minato-Inokawa

et al. 2020

BMJ Open Diab Res Care

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IntroductionDeterminants and correlates of a novel index of adipose tissue insulin resistance (AT-IR) (the product of fasting insulin and free fatty acid concentrations) were investigated in Japanese women without diabetes and obesity.Research design and methodsCross-sectional associations of AT-IR with fat mass and distribution, and IR-related cardiometabolic variables were examined in 210 young and 148 middle-aged women whose average body mass index (BMI) was <23 kg/m2 and waist was <80 cm. Multivariate linear regression analyses were used to identify most important determinants of AT-IR.ResultsYoung and middle-aged women did not differ in AT-IR (3.5±2.7 and 3.2±2.1, respectively). In both young and middle-aged women, AT-IR was positively associated with trunk/leg fat ratio, a sophisticated measure of abdominal fat accumulation, fasting plasma glucose (FPG), fasting triglycerides (FTG), serum alanine aminotransferase and γ-glutamyl-transpeptidase (all p<0.05). Furthermore, in middle-aged but not in young women, AT-IR showed positive associations with BMI, waist, fat mass index, low-density lipoprotein cholesterol, apolipoprotein B and systolic and diastolic blood pressure (BP) (all p<0.05). AT-IR showed no association with hemoglobin A1c, high-density lipoprotein (HDL) cholesterol and apolipoprotein A1 in two groups of women. On multivariate analysis including waist, FPG, FTG, HDL cholesterol and systolic BP as independent variables, FPG, FTG and HDL cholesterol emerged as independent determinants of AT-IR in young women (cumulative R2=0.141) and waist in middle-aged women (cumulative R2=0.056). In a model which included trunk/leg fat ratio instead of waist, trunk/leg fat ratio and systolic BP were determinants of AT-IR in middle-aged women (cumulative R2=0.093). Results did not alter in young women.ConclusionsAT-IR may be a simple and useful surrogate index of adipose tissue insulin resistance even in populations without diabetes and obesity.

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Adipose Tissue Insulin Resistance in Youth on the Spectrum From Normal Weight to Obese and From Normal Glucose Tolerance to Impaired Glucose Tolerance to Type 2 Diabetes

Cited by 89 publications

References 39 publications

Mitochondrial-Derived Peptides Are Down Regulated in Diabetes Subjects

Mitochondrial-Derived Peptides Are Down Regulated in Diabetes Subjects

Cdc42: A Novel Regulator of Insulin Secretion and Diabetes-Associated Diseases

Determinants and correlates of adipose tissue insulin resistance index in Japanese women without diabetes and obesity

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