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Insulin resistance and impaired mitochondrial function in obese adolescent girls.

ABSTRACT: BACKGROUND:Mitochondrial dysfunction plays a role in the development of muscle insulin resistance (IR) and the accumulation of intramyocellular lipid (IMCL) in skeletal muscle that can, in turn, interfere with insulin signaling. The purpose of this study was to assess mitochondrial function (MF) and IMCL in obese adolescent girls with and without IR to determine whether: (1) Girls with IR have impaired MF, and (2) impaired MF in girls with IR is related to higher IMCL. METHODS:We examined 22 obese girls aged 13-21 years old for IR [defined as a homeostasis model assessment of insulin resistance (HOMA-IR) value >4. Phosphorus magnetic resonance spectroscopy (31P-MRS) and proton magnetic resonance spectroscopy (1H-MRS), respectively, were used to determine MF and IMCL of the soleus muscle along with magnetic resonance imaging (MRI) measures of visceral, subcutaneous, and total adipose tissue (VAT, SAT, and TAT) in girls with HOMA-IR >4 (insulin-resistant group) versus HOMA-IR ? 4 (insulin-sensitive group). Serum lipids and waist-to-hip ratio (W/H) were also measured. RESULTS:Girls with IR (n=8) did not differ from the insulin-sensitive group (n=14) for age, bone age, weight, VAT, SAT, TAT, or IMCL. However, the insulin-resistant group had higher W/H. Additionally the insulin-resistance group had a lower log rate of postexercise phosphocreatine (PCr) recovery (ViPCr) and a higher log PCr recovery constant (tau), indicative of impaired MF. CONCLUSIONS:Obese girls with increased IR have impaired mitochondrial function. This association is not mediated by alterations in IMCL or adipose tissue. Further studies are necessary to determine whether there is a causal relation between impaired mitochondrial function and IR in obesity and mediators of such a relationship.

SUBMITTER: Slattery MJ

PROVIDER: S-EPMC3942687 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature

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Insulin resistance and impaired mitochondrial function in obese adolescent girls.

Slattery Meghan J MJ Bredella Miriam A MA Thakur Hena H Torriani Martin M Misra Madhusmita M

Metabolic syndrome and related disorders 20131119 1

<h4>Background</h4>Mitochondrial dysfunction plays a role in the development of muscle insulin resistance (IR) and the accumulation of intramyocellular lipid (IMCL) in skeletal muscle that can, in turn, interfere with insulin signaling. The purpose of this study was to assess mitochondrial function (MF) and IMCL in obese adolescent girls with and without IR to determine whether: (1) Girls with IR have impaired MF, and (2) impaired MF in girls with IR is related to higher IMCL.<h4>Methods</h4>We ...[more]

PMID: 24251951

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Project description:BackgroundObesity and diabetes mellitus are associated with an increased risk of pancreatic cancer. These associations may be secondary to consequences of peripheral insulin resistance, pancreatic β-cell dysfunction, or hyperglycemia itself. Hemoglobin A1c (HbA1c) is a measure of hyperglycemia, whereas plasma insulin and proinsulin are markers of peripheral insulin resistance, and the proinsulin to insulin ratio marks pancreatic β-cell dysfunction.MethodsThis was a prospective, nested case-control study of 449 case patients and 982 control subjects with prediagnostic blood samples and no diabetes history from five prospective US cohorts followed through 2008. Two or three control subjects were matched to each case patient by year of birth, cohort, smoking, and fasting status. Pancreatic cancer risk was assessed by prediagnostic HbA1c, insulin, proinsulin, and proinsulin to insulin ratio with multivariable-adjusted logistic regression. All P values were two-sided.ResultsThe highest vs lowest quintiles of HbA1c, insulin, and proinsulin were associated with with an increased risk for pancreatic cancer (odds ratio [OR] = 1.79; 95% confidence interval [CI] = 1.17 to 2.72, P trend = .04 for HbA1c; OR = 1.57; 95% CI = 1.08 to 2.30; Ptrend = .002 for insulin; and OR = 2.22; 95% CI = 1.50 to 3.29; P trend < .001 for proinsulin). Proinsulin to insulin ratio was not associated with pancreatic cancer risk. Results were similar across studies (all P heterogeneity > .29). In cancers developing 10 or more years after blood collection, the associations with insulin and proinsulin became stronger (highest vs lowest quintile, OR = 2.77; 95% CI = 1.28 to 5.99 for insulin and OR = 3.60; 95% CI = 1.68 to 7.72 for proinsulin). In mutually adjusted models including HbA1c, insulin, and proinsulin, only proinsulin remained statistically significant ( highest vs lowest quintile, OR = 2.55; 95% CI = 1.54 to 4.21; Ptrend < .001).ConclusionsAmong participants from five large prospective cohorts, circulating markers of peripheral insulin resistance, rather than hyperglycemia or pancreatic β-cell dysfunction, were independently associated with pancreatic cancer risk.

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Insulin resistance and impaired mitochondrial function in obese adolescent girls.

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Insulin resistance and impaired mitochondrial function in obese adolescent girls.

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