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Diabetes profoundly alters fuel metabolism; both insulin deficiency and insulin resistance are characterized by inefficient mitochondrial coupling and excessive production of reactive oxygen species (ROS) despite their association with normal to high oxygen consumption. Altered mitochondrial function in diabetes can be traced to insulin's pivotal role in maintaining mitochondrial proteome abundance and quality by enhancing mitochondrial biogenesis and preventing proteome damage and degradation, respectively. Although insulin enhances gene transcription, it also induces decreases in amino acids. Thus, if amino acid depletion is not corrected, increased transcription will not result in enhanced translation of transcripts to proteins. Mitochondrial biology varies among tissues, and although most studies in humans are performed in skeletal muscle, abnormalities have been reported in multiple organs in preclinical models of diabetes. Nutrient excess, especially fat excess, alters mitochondrial physiology by driving excess ROS emission that impairs insulin action. Excessive ROS irreversibly damages DNA and proteome with adverse effects on cellular functions. In insulin-resistant people, aerobic exercise stimulates both mitochondrial biogenesis and efficiency concurrent with enhancement of insulin action. This Review discusses the association between both insulin-deficient and insulin-resistant diabetes and alterations in mitochondrial proteome homeostasis and function that adversely affect cellular functions, likely contributing to many diabetic complications.

Objective: To examine the relationships of 25-hydroxyvitamin D (25-OHD) levels with the measures of insulin resistance and cardiovascular risk, and identify the clinical factors associated with low 25-OHD in young obese children., Design and Methods: Data from 83 children ages 2-6 years seen for obesity care (clinic latitude 42°N) were analyzed. Insulin resistance [homeostasis model assessment of insulin resistance (HOMA-IR)] and cardiovascular risks were examined in relationship to 25-OHD levels using correlation statistics. χ2 and logistic regression models were applied to identify the factors associated with vitamin D deficiency (25-OHD levels <20 ng/mL) and insufficiency (<30 ng/mL)., Results: Children's mean age was mean 4.9 years and they were predominantly Hispanic. Mean body mass index (BMI) Z-score was 3.2 and mean HOMA-IR was 2.8. Mean 25-OHD was 30.9 ng/mL (6% <20 ng/mL and 46% 20-29 ng/mL). There were no significant correlations between 25-OHD and BMI (Spearman's ρ=-0.096, p=0.389), BMI Z-score (Spearman's ρ=0.104, p=0.350), HOMA-IR (Spearman's ρ=-0.144, p=0.269), total cholesterol (Spearman's ρ=-0.028, p=0.833), or triglycerides (Spearman's ρ=-0.026, p=0.846). Vitamin D deficiency was significantly associated with older age, lower milk intake, and testing in winter months. 25-OHD level <30 ng/mL was associated with older age, African-American and Hispanic race/ethnicity, and testing in winter months. All factors retained significance in a multivariate logistic regression model, with African-American (odds ratio=14.4) and Hispanic (odds ratio=7.2) race/ethnicity being the strongest predictors of 25-OHD levels <30 ng/mL., Conclusions: In these children, 25-OHD was not associated with insulin resistance or cardiovascular risks. Considering age, race/ethnicity, diet, and season may help identify young obese children needing vitamin D management.