Browsing by Subject "Diabetes Mellitus -- Type 2"

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    12-Lipoxygenase Inhibitor Improves Functions of Cytokine-Treated Human Islets and Type 2 Diabetic Islets
    (Oxford University Press, 2017-08-01) Ma, Kaiwen; Xiao, An; Park, So Hyun; Glenn, Lindsey; Jackson, Laura; Barot, Tatvam; Weaver, Jessica R.; Taylor-Fishwick, David A.; Luci, Diane K.; Maloney, David J.; Mirmira, Raghavendra G.; Imai, Yumi; Nadler, Jerry L.; Pediatrics, School of Medicine
    Context: The 12-lipoxygenase (12-LO) pathway produces proinflammatory metabolites, and its activation is implicated in islet inflammation associated with type 1 and type 2 diabetes (T2D). Objectives: We aimed to test the efficacy of ML355, a highly selective, small molecule inhibitor of 12-LO, for the preservation of islet function. Design: Human islets from nondiabetic donors were incubated with a mixture of tumor necrosis factor α , interluekin-1β, and interferon-γ to model islet inflammation. Cytokine-treated islets and human islets from T2D donors were incubated in the presence and absence of ML355. Setting: In vitro study. Participants: Human islets from organ donors aged >20 years of both sexes and any race were used. T2D status was defined from either medical history or most recent hemoglobin A1c value >6.5%. Intervention: Glucose stimulation. Main Outcome Measures: Static and dynamic insulin secretion and oxygen consumption rate (OCR). Results: ML355 prevented the reduction of insulin secretion and OCR in cytokine-treated human islets and improved both parameters in human islets from T2D donors. Conclusions: ML355 was efficacious in improving human islet function after cytokine treatment and in T2D islets in vitro. The study suggests that the blockade of the 12-LO pathway may serve as a target for both form of diabetes and provides the basis for further study of this small molecule inhibitor in vivo.
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    Comparison of β-Cell Function Between Overweight/Obese Adults and Adolescents Across the Spectrum of Glycemia
    (American Diabetes Association, 2018-02) Chen, Melinda E.; Chandramouli, Aaditya G.; Considine, Robert V.; Hannon, Tamara S.; Mather, Kieren J.; Pediatrics, School of Medicine
    OBJECTIVE: Type 2 diabetes is a growing health problem among both adults and adolescents. To better understand the differences in the pathogenesis of diabetes between these groups, we examined differences in β-cell function along the spectrum of glucose tolerance. RESEARCH DESIGN AND METHODS: We evaluated 89 adults and 50 adolescents with normal glucose tolerance (NGT), dysglycemia, or type 2 diabetes. Oral glucose tolerance test results were used for C-peptide and insulin/glucose minimal modeling. Model-derived and direct measures of insulin secretion and insulin sensitivity were compared across glycemic stages and between age-groups at each stage. RESULTS: In adolescents with dysglycemia, there was marked insulin resistance (insulin sensitivity index: adolescents, median [interquartile range] 1.8 [1.1-2.4] × 10-4; adults, 5.0 [2.3-9.9]; P = 0.01). The nature of β-cell dysfunction across stages of dysglycemia differed between the groups. We observed higher levels of secretion among adolescents than adults (total insulin secretion: NGT, 143 [103-284] × 10-9/min adolescent vs. 106 [71-127], P = 0.001); adults showed stepwise impairments in static insulin secretion (NGT, 7.5 [4.0-10.3] × 10-9/min; dysglycemia, 5.0 [2.3-9.9]; type 2 diabetes, 0.7 [0.1-2.45]; P = 0.003), whereas adolescents showed diabetes-related impairment in dynamic secretion (NGT, 1,905 [1,630-3,913] × 10-9; dysglycemia, 2,703 [1,323-3,637]; type 2 diabetes, 1,189 [269-1,410]; P = 0.001). CONCLUSIONS: Adults and adolescents differ in the underlying defects leading to dysglycemia, and in the nature of β-cell dysfunction across stages of dysglycemia. These results may suggest different approaches to diabetes prevention in youths versus adults.
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    Effect of collaborative depression treatment on risk for diabetes: A 9-year follow-up of the IMPACT randomized controlled trial
    (PLOS, 2018-08-23) Khambaty, Tasneem; Callahan, Christopher M.; Stewart, Jesse C.; Medicine, School of Medicine
    Considerable epidemiologic evidence and plausible biobehavioral mechanisms suggest that depression is an independent risk factor for diabetes. Moreover, reducing the elevated diabetes risk of depressed individuals is imperative given that both conditions are leading causes of death and disability. However, because no prior study has examined clinical diabetes outcomes among depressed patients at risk for diabetes, the question of whether depression treatment prevents or delays diabetes onset remains unanswered. Accordingly, we examined the effect of a 12-month collaborative care program for late-life depression on 9-year diabetes incidence among depressed, older adults initially free of diabetes. Participants were 119 primary care patients [M (SD) age: 67.2 (6.9) years, 41% African American] with a depressive disorder but without diabetes enrolled at the Indiana sites of the Improving Mood-Promoting Access to Collaborative Treatment (IMPACT) trial. Incident diabetes cases were defined as diabetes diagnoses, positive laboratory values, or diabetes medication prescription, and were identified using electronic medical record and Medicare/Medicaid data. Surprisingly, the rate of incident diabetes in the collaborative care group was 37% (22/59) versus 28% (17/60) in the usual care group. Even though the collaborative care group exhibited greater reductions in depressive symptom severity (p = .024), unadjusted (HR = 1.29, 95% CI: 0.69-2.43, p = .428) and adjusted (HR = 1.18, 95% CI: 0.61-2.29, p = .616) Cox proportional hazards models indicated that the risk of incident diabetes did not differ between the treatment groups. Our novel preliminary findings raise the possibility that depression treatment alone may be insufficient to reduce the excess diabetes risk of depressed, older adults.