Browsing by Subject "insulin sensitivity"

Now showing 1 - 4 of 4
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    The Changing Face of Diabetes in Youth: Lessons Learned from Studies of Type 2 Diabetes
    (Wiley, 2015-09) Hannon, Tamara S.; Arslanian, Silva A.; Department of Pediatrics, IU School of Medicine
    The incidence of youth type 2 diabetes (T2D), linked with obesity and declining physical activity in high-risk populations, is increasing. Recent multicenter studies have led to a number of advances in our understanding of the epidemiology, pathophysiology, diagnosis, treatment, and complications of this disease. As in adult T2D, youth T2D is associated with insulin resistance, together with progressive deterioration in β cell function and relative insulin deficiency in the absence of diabetes-related immune markers. In contrast to adult T2D, the decline in β cell function in youth T2D is three- to fourfold faster, and therapeutic failure rates are significantly higher in youth than in adults. Whether the more aggressive nature of youth T2D is driven by genetic heterogeneity or physiology/metabolic maladaptation is yet unknown. Besides metformin, the lack of approved pharmacotherapeutic agents for youth T2D that target the pathophysiological mechanisms is a major barrier to optimal diabetes management. There is a significant need for effective therapeutic options, in addition to increased prevention, to halt the projected fourfold increase in youth T2D by 2050 and the consequences of heightened diabetes-related morbidity and mortality at younger ages.
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    Methods for Measuring Risk for Type 2 Diabetes in Youth: the Oral Glucose Tolerance Test (OGTT)
    (Springer, 2018-08) Chen, Melinda E.; Aguirre, Rebecca S.; Hannon, Tamara S.; Pediatrics, School of Medicine
    Purpose of Review The oral glucose tolerance test (OGTT) is used both in clinical practice and research to assess glucose tolerance. In addition, the OGTT is utilized for surrogate measures of insulin sensitivity and the insulin response to enteral glucose and has been widely applied in the evaluation of β-cell dysfunction in obesity, prediabetes, and type 2 diabetes. Here we review the use of the OGTT and the OGTT-derived indices for measurement of risk markers for type 2 diabetes in youth. Recent Findings Advantages of using the OGTT for measures of diabetes risk include its accessibility and the incorporation of physiological contributions of the gut-pancreas axis in the measures of insulin response to glucose. Mathematical modeling expands the potential gains from the OGTT in physiology and clinical research. Disadvantages include individual differences in the rate of glucose absorption that modify insulin responses, imperfect control of the glycemic stimulus, and poor intraindividual reproducibility. Summary Available research suggests the OGTT provides valuable information about the development of impaired glycemic control and β-cell function in obese youth along the spectrum of glucose tolerance.
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    Mitochondrial DNA Copy Number, Insulinemic Potential of Lifestyle, and Colorectal Cancer
    (2020-03) Yang, Keming; Nan, Hongmei; Forman, Michele R.; Graham, Brett H.; Han, Jiali; Monahan, Patrick O.
    Because colorectal cancer (CRC) is the fourth most common cancer and the second leading cause of cancer death in the US, identifying biomarkers that might inform disease prevention and early diagnosis is of great public health importance. Mitochondria are key cytoplasmic organelles containing an independent genome, i.e., mitochondrial DNA (mtDNA). It has been increasingly recognized that mtDNA copy number (mtDNAcn) is a biomarker for mitochondrial function and cellular oxidative stress. To date, the few studies that have assessed associations between mtDNAcn and CRC outcomes have yielded inconsistent findings. Further, no epidemiologic study has examined the relationship between insulinemic potential of lifestyle and mtDNAcn. Therefore, in this dissertation, three studies were conducted using data from the Nurses’ Health Study and the Health Professionals Follow-Up Study. First, the association between pre-diagnostic leukocyte mtDNAcn and CRC risk was studied in a nested casecontrol study (324 cases/658 controls). Lower mtDNAcn was significantly associated with increased risk of CRC and proximal colon cancer. That inverse association remained significant among individuals with ≥ 8 years’ follow-up since blood collection, suggesting that mtDNAcn might serve as a long-term predictor of CRC risk. Second, possible associations of pre-diagnostic mtDNAcn with overall and CRC-specific survival were examined among 587 CRC patients. MtDNAcn was not significantly associated with survival overall or in subgroups by cancer location, grade, or stage. Among current smokers, there was an inverse association between one standard deviation (SD) decrease in mtDNAcn and increased overall death risk. Among patients diagnosed at or before 70.5 years of age and those with anti-inflammatory diets, reduced mtDNAcn was associated with lower CRC-specific death risk. Lastly, the cross-sectional association between empirical lifestyle index for hyperinsulinemia (ELIH) and mtDNAcn was investigated among 2,835 subjects without major chronic diseases (cancers, diabetes, and cardiovascular diseases). A significant inverse association was found: least-squares means ± SD of mtDNAcn z-score decreased dramatically across ELIH quintiles. Overall, the findings from this dissertation will contribute to the evaluation of mtDNAcn as a potential biomarker for CRC risk and prognosis, and inform future interventions designed to reduce the insulinemic potential of lifestyle factors to preserve mitochondrial function.
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    Pre-pregnancy habitual intake of vitamin D from diet and supplements in relation to risk of gestational diabetes mellitus: a prospective cohort study
    (Wiley, 2017) Bao, Wei; Song, Yiqing; Bertrand, Kimberly A.; Tobias, Dierdre K.; Olsen, Sjurdur F.; Chavarro, Jorge E.; Mills, James L.; Hu, Frank B.; Zhang, Cuilin; Epidemiology, School of Public Health
    Background Vitamin D may play a pivotal role in regulating insulin secretion and insulin sensitivity. However, the impact of vitamin D intake either from diet or from supplements on the development of gestational diabetes mellitus (GDM) remains unknown. We prospectively examined the association of pre-pregnancy habitual intake of vitamin D from diet and supplements with risk of incident GDM in a well-established cohort. Methods We included 21,356 singleton pregnancies from 15,225 women in the Nurses' Health Study II cohort. Diet information, including vitamin D intakes from food sources and supplements, was assessed in 1991 and every four years thereafter by validated food frequency questionnaires. We used log-binomial models with generalized estimating equations to estimate the relative risks (RRs) and 95% confidence intervals (CIs). Results We documented 865 incident GDM cases during 10 years of follow-up. After adjustment for age, parity, race/ethnicity, family history of diabetes, dietary and lifestyle factors, and body mass index, the RRs (95% CIs) of GDM risk associated with supplemental vitamin D intake of 0, 1–399, ≥ 400 IU/d were 1.00 (reference), 0.80 (0.67-0.96), and 0.71 (0.56-0.90), respectively (P for trend = 0.002). Dietary and total vitamin D intakes were also inversely associated with GDM risk, but the associations were not statistically significant. Conclusions Pre-pregnancy supplemental vitamin D intake was significantly and inversely associated with risk of GDM. Our study indicates potential benefits of increasing vitamin D intake from supplements in the prevention of GDM in women of reproductive age.