Birth weight, type 2 diabetes, and insulin resistance in Pima Indian children and young adults

Individuals born with a low birth weight (LBW) have an increased prevalence of type 2 diabetes, but the mechanisms responsible for this association are unknown. Given the important role of insulin resistance in the pathogenesis of type 2 diabetes, we examined insulin sensitivity in a rat model of LBW due to intrauterine fetal stress. During the last 7 days of gestation, rat dams were treated with dexamethasone and insulin sensitivity was assessed in the LBW offspring by a hyperinsulinemic euglycemic clamp. The LBW group had liver-specific insulin resistance associated with increased levels of PEPCK expression. These changes were associated with pituitary hyperplasia of the ACTH-secreting cells, increased morning plasma ACTH concentrations, elevated corticosterone secretion during restraint stress, and an ∼70% increase in 24-h urine corticosterone excretion. These data support the hypothesis that prenatal stress can result in chronic hyperactivity of the hypothalamic-pituitary-adrenal axis, resulting in increased plasma corticosterone concentrations, upregulation of hepatic gluconeogenesis, and hepatic insulin resistance.

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A-18 Early Pattern of Cognitive Changes Associated with Insulin Resistance in a Sample of Young Adults

Archives of Clinical Neuropsychology ◽

10.1093/arclin/acab062.36 ◽

2021 ◽

Vol 36 (6) ◽

pp. 1059-1059

Author(s):

Sana Arastu ◽

Juan Gonzalez ◽

Nicole E Greenberg ◽

Emma L Lucas ◽

Tonita E Wroolie ◽

...

Keyword(s):

Insulin Resistance ◽

Type 2 Diabetes ◽

Young Adults ◽

Executive Functioning ◽

Color Word ◽

Neuropsychological Functioning ◽

Fine Motor ◽

Cognitive Changes ◽

Motor Abilities

Abstract Objective Insulin resistance increases the risk of developing type 2 diabetes and subsequently cardiovascular and cerebrovascular disease. It is also linked to neurocognitive disorders and accelerated cognitive aging (Ekblad et al, 2017; Levine, Harrati, & Crimmins, 2018). Using baseline data from a longitudinal study in a sample of 126 cognitively intact adults aged 25–50 years (36.5% males), we assessed cognitive performance in relation to insulin resistance to determine whether an early prodromal pattern of cognitive changes exists prior to advanced metabolic disease. Methods Steady state plasma glucose (SSPG) was used to measure insulin resistance. Multivariate regression analyses were conducted using age, years of education, body mass index (BMI), and SSPG as predictors of neuropsychological functioning. In-person and tele-neuropsychological assessment was administered using standard neuropsychological measures. Results Higher insulin resistance was associated with significantly worse attention (WAIS-III Digit Span total; B = -0.018, p = 0.03), executive functioning (D-KEFS Color-Word Inhibition/Switching; B = 0.047, p = 0.04) and dominant fine motor abilities (Purdue Pegboard; B = -0.008, p = 0.02). Higher insulin resistance was also associated with trend level worsening of other measures of executive functioning, namely D-KEFS Trails 4 (B = 0.099, p = 0.07) and DKEFS Color-Word Inhibition errors (B = 0.007, p = 0.09). Conclusions In young adults, higher insulin resistance was associated with declines in attention, executive functioning, and fine motor abilities. This early pattern of subtle cognitive changes associated with higher insulin resistance seen in this sample of younger adults is consistent with later cognitive declines found in type 2 diabetes and vascular neurocognitive disorder, namely declines in attention, executive functioning, and motor abilities with eventual memory declines in advanced disease.

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Mitochondrial Function in Skeletal Muscle Is Normal and Unrelated to Insulin Action in Young Men Born with Low Birth Weight

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2008-0630 ◽

2008 ◽

Vol 93 (10) ◽

pp. 3885-3892 ◽

Cited By ~ 57

Author(s):

Charlotte Brøns ◽

Christine B. Jensen ◽

Heidi Storgaard ◽

Amra Alibegovic ◽

Stine Jacobsen ◽

...

Keyword(s):

Insulin Resistance ◽

Type 2 Diabetes ◽

Skeletal Muscle ◽

Birth Weight ◽

Low Birth Weight ◽

Mitochondrial Dysfunction ◽

Mitochondrial Function ◽

Young Men ◽

Hepatic Insulin Resistance

Objective: Low birth weight (LBW) is an independent risk factor of insulin resistance and type 2 diabetes. Recent studies suggest that mitochondrial dysfunction and impaired expression of genes involved in oxidative phosphorylation (OXPHOS) may play a key role in the pathogenesis of insulin resistance in aging and type 2 diabetes. The aim of this study was to determine whether LBW in humans is associated with mitochondrial dysfunction in skeletal muscle. Methods: Mitochondrial capacity for ATP synthesis was assessed by 31phosphorus magnetic resonance spectroscopy in forearm and leg muscles in 20 young, lean men with LBW and 26 matched controls. On a separate day, a hyperinsulinemic euglycemic clamp with excision of muscle biopsies and dual-energy x-ray absorptiometry scanning was performed. Muscle gene expression of selected OXPHOS genes was determined by quantitative real-time PCR. Results: The LBW subjects displayed a variety of metabolic and prediabetic abnormalities, including elevated fasting blood glucose and plasma insulin levels, reduced insulin-stimulated glycolytic flux, and hepatic insulin resistance. Nevertheless, in vivo mitochondrial function was normal in LBW subjects, as was the expression of OXPHOS genes. Conclusions: These data support and expand previous findings of abnormal glucose metabolism in young men with LBW. In addition, we found that the young, healthy men with LBW exhibited hepatic insulin resistance. However, the study does not support the hypothesis that muscle mitochondrial dysfunction per se is the underlying key metabolic defect that explains or precedes whole body insulin resistance in LBW subjects at risk for developing type 2 diabetes.

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