Browsing by Subject "Prediabetes"
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Item Characteristics of Obstructive Sleep Apnea Across the Spectrum of Glucose Tolerance in Obese Adolescents.(Frontiers Media, 2018-06-01) Hannon, Tamara S.; Watson, Sara E.; Jalou, Hasnaa E.; Chakravorty, Sangeeta; Mather, Kieren J.; Arslanian, Silva A.; Pediatrics, School of MedicineBackground: It is not known if dysglycemia and sleep-disordered breathing are linked in adolescents, as in adults. Objective: To perform a pilot study evaluating measures of sleep-disordered breathing across the spectrum of glucose tolerance in obese adolescents. We hypothesized that dysglycemia would be associated with sleep-disordered breathing. Participants/methods: This was a prospective, cross-sectional clinical pilot study that included 57 adolescents [body mass index (BMI) 38.9 ± 8.4 kg/m2] aged 12-18 years (14.5 ± 1.6) with normal glucose tolerance (NGT), or dysglycemia [impaired glucose tolerance (IGT) or type 2 diabetes (T2D)]. Measures: Anthropometrics, overnight polysomnogram, and oral glucose tolerance tests were performed. Participant characteristics and outcome measures were compared by glucose tolerance status. Correlational analyses were conducted to assess the associations between variables of interest. Results: Participants with dysglycemia (n = 21) were not different from those with NGT (n = 36) for BMI, waist circumference, body fat, or sleep characteristics. Nocturnal oxygen desaturation was associated with higher BMI (r = -0.334, p = 0.012). The apnea-hypopnea index (AHI) was not associated with physical and metabolic parameters. Although participants with dysglycemia tended to have higher AHIs (median 3.2, 2.2, and 1.6 events/h for T2D, IGT, and NGT, respectively), there was not a linear relationship between measures of glycemia and AHI. Conclusion: Further study with a larger proportion of youth with prediabetes and T2D is necessary to determine whether evaluation for sleep-disordered breathing is uniformly warranted.Item Depressive symptoms and metabolic markers of risk for type 2 diabetes in obese adolescents(Wiley, 2013-11) Hannon, Tamara S.; Rofey, Dana L.; Lee, SoJung; Arslanian, Silva A.; Pediatrics, School of MedicineOBJECTIVE: Although higher rates of depression are found among individuals with type 2 diabetes, it remains unknown if the presence of depressive symptoms is associated with heightened metabolic risk for the development of type 2 diabetes among youth. The objective of this study was to evaluate whether depressive symptoms in obese adolescents are associated with impaired β-cell function relative to insulin sensitivity [oral disposition index (oDI)] and/or dysglycemia or prediabetes, predictors of type 2 diabetes development. RESEARCH DESIGN AND METHODS: Fasting and oral glucose tolerance test (OGTT)-derived indices of glucose tolerance, insulin sensitivity, secretion, and oDI were evaluated in obese youth (n = 56, age 15.0 ± 1.6 yr, 68% female). The Children's Depression Inventory was utilized to determine depressive symptomatology. RESULTS: Despite no association between depressive symptoms and measures of adiposity, youth with higher depressive symptoms had (i) significantly higher fasting and stimulated glucose levels (13% higher glucose area under the OGTT curve), (ii) ∼50% lower oDI, and (iii) a 50% frequency of prediabetes. CONCLUSIONS: These data point to an important relationship between depressive symptoms and a heightened metabolic risk for type 2 diabetes in obese adolescents, including prediabetes and impairment in β-cell function relative to insulin sensitivity. While the directionality of these relationships is unknown, it should be determined if treating one disorder improves the other or vice versa.Item Early Impairment of Insulin Sensitivity, β-Cell Responsiveness, and Insulin Clearance in Youth with Stage 1 Type 1 Diabetes(Oxford University Press, 2021) Galderisi, Alfonso; Moran, Antoinette; Evans-Molina, Carmella; Martino, Mariangela; Santoro, Nicola; Caprio, Sonia; Cobelli, Claudio; Pediatrics, School of MedicineContext: Clinical onset of type 1 diabetes (Stage 3 T1D) is preceded by a presymptomatic phase characterized by multiple islet autoantibodies with normal glucose tolerance (Stage 1 T1D). Objective: The aim was to explore the metabolic phenotypes of β-cell function and insulin sensitivity and clearance in normoglycemic youth with Stage 1 T1D and compare them with healthy nonrelated peers during a 3-hour oral glucose tolerance test (OGTT). Methods: Twenty-eight lean youth, 14 with ≥2 islet autoantibodies (cases) and 14 healthy controls underwent a 3-hour 9-point OGTT with measurement of glucose, C-peptide, and insulin. The oral minimal model was used to quantitate β-cell responsiveness (φtotal) and insulin sensitivity (SI), allowing assessment of β-cell function by the disposition index (DI=φtotal×SI). Fasting insulin clearance (CL0) was calculated as the ratio between the fasting insulin secretion rate (ISR) and plasma insulin levels (ISR0/I0), while postload clearance (CL180) was estimated by the ratio of AUC of ISR over the plasma insulin AUC for the 3-hour OGTT (ISRAUC/IAUC). Participants with impaired fasting glucose, impaired glucose tolerance, or any OGTT glucose concentration ≥200 mg/dL were excluded. Results: Cases (10.5 years [8, 15]) exhibited reduced DI (P < .001) due to a simultaneous reduction in both φtotal (P < 0.001) and SI (P = .008) compared with controls (11.5 years [10.4, 14.9]). CL0 and CL180 were lower in cases than in controls (P = .005 and P = .019). Conclusion: Presymptomatic Stage 1 T1D in youth is associated with reduced insulin sensitivity and lower β-cell responsiveness, and the presence of blunted insulin clearance.Item Effects of a Community-based Lifestyle Intervention on Change in Physical Activity Among Economically Disadvantaged Adults With Prediabetes(Taylor and Francis, 2016) Hays, Laura M.; Hoen, Helena M.; Slaven, James E.; Finch, Emily A.; Marrero, David G.; Saha, Chandan; Ackermann, Ronald T.; School of NursingItem Expert Clinical Interpretation of Continuous Glucose Monitor Reports From Individuals Without Diabetes(Sage, 2025-02-12) Spartano, Nicole L.; Prescott, Brenton; Walker, Maura E.; Shi, Eleanor; Venkatesan, Guhan; Fei, David; Lin, Honghuang; Murabito, Joanne M.; Ahn, David; Battelino, Tadej; Edelman, Steven V.; Fleming, G. Alexander; Freckmann, Guido; Galindo, Rodolfo J.; Joubert, Michael; Lansang, M. Cecilia; Mader, Julia K.; Mankovsky, Boris; Mathioudakis, Nestoras N.; Mohan, Viswanathan; Peters, Anne L.; Shah, Viral N.; Spanakis, Elias K.; Waki, Kayo; Wright, Eugene E.; Zilbermint, Mihail; Wolpert, Howard A.; Steenkamp, Devin W.; Medicine, School of MedicineBackground: Clinical interpretation of continuous glucose monitoring (CGM) data for people without diabetes has not been well established. This study aimed to investigate concordance among CGM experts in recommending clinical follow-up for individuals without diabetes, based upon their independent review of CGM data. Methods: We sent a survey out to expert clinicians (n = 18) and asked them to evaluate 20 potentially challenging Dexcom G6 Pro CGM reports (and hemoglobin A1c [HbA1c] and fasting venous blood glucose levels) from individuals without diabetes. Clinicians reported whether they would recommend follow-up and the reasoning for their decision. We performed Fleiss Kappa interrater reliability to determine agreement among clinicians. Results: More than half of expert clinicians (56-100%, but no clear consensus) recommended follow-up to individuals who spent >2% time above range (>180 mg/dL), even if HbA1c <5.7% and fasting glucose <100 mg/dL. There were no observed trends for recommending follow-up based on mean glucose or glucose management indicator. Overall, we observed poor agreement in recommendations for who should receive follow-up based on their CGM report (Fleiss Kappa = 0.36). Conclusions: High discordance among expert clinicians when interpreting potentially challenging CGM reports for people without diabetes highlights the need for more research in developing normative data for people without diabetes. Future work is required to develop CGM criteria for identifying potentially high-risk individuals who may progress to prediabetes or type 2 diabetes.Item Forever-Fit Summer Camp: The Impact of a 6-Week Summer Healthy Lifestyle Day Camp on Anthropometric, Cardiovascular, and Physical Fitness Measures in Youth With Obesity(SAGE, 2020-01) El Mikati, Hala K.; Boateng, Anthony O.; McKinney, Brett M.; Haberlin-Pittz, Katie; Pike, Julie; Perry, Patrick; Hannon, Tamara S.; Yazel-Smith, Lisa; Medicine, School of MedicinePediatric obesity is a public health concern with lifestyle intervention as the first-line treatment. Forever-Fit Summer Camp (FFSC) is a 6-week summer day program offering physical activity, nutrition education, and well-balanced meals to youth at low cost. The aim of the study was to assess the efficacy of this program that does not emphasize weight loss rather emphasizes healthy behaviors on body mass index, cardiovascular and physical fitness. Methods: The inclusion criteria were adolescents between 8 and 12 years and body mass index (BMI) ≥85th percentile. The data were collected at baseline and week 6 (wk-6) and was analyzed for 2013-2018 using paired-sample t tests. Results: The participants' (N = 179) average age was 10.6 ± 1.6 years with a majority of females (71%) and black race/ethnicity (70%). At wk-6, BMI and waist circumference decreased by 0.8 ± 0.7 kg/m2 and 1.0 ± 1.3 in, respectively. Resting heart rate, diastolic and systolic blood pressure decreased by 8.5 ± 11.0 bpm, 6.3 ± 8.8 mmHg, and 6.4 ± 10.1 mmHg, respectively. The number of pushups, curl-ups, and chair squats were higher by 5.8 ± 7.5, 6.7 ± 9.1, and 7.7 ± 8.5, respectively. Conclusion: The FFSC is efficacious for improving BMI, cardiovascular, and physical fitness in the short term. The effect of similar episodic efforts that implement healthy lifestyle modifications throughout the school year should be investigated.Item Higher selenium was associated with higher risk of diabetes: Consistent evidence from longitudinal and cross-sectional studies based on nail and serum selenium measures(Elsevier, 2022-09-20) Shao, Ranqi; Su, Liqin; Li, Li; Wu, Jinghuan; He, Xiaohong; Mao, Deqian; Cheng, Yibin; Liu, Jingyi; Chen, Chen; Jin, Yinlong; Gao, Sujuan; Biostatistics and Health Data Science, School of MedicineAlthough the association between selenium (Se) and diabetes has been well-discussed in recent years, few studies have focused on the effects of long-term natural Se exposure and rarely concerned the effects of different Se biomarkers. To address this question, we carried out a 7-year longitudinal study on older adults aged over 65 and another cross-sectional study on middle-aged and older adults aged 40 and above from Chinese soil Se-deplete and Se-optimum areas. Cox proportional hazard models were used to evaluate the associations between nail Se levels and incidence risk of diabetes. Unconditional logistic regression models and analysis of variance models were used to examine the associations between serum Se levels and the prevalence risk of diabetes. The nail and serum Se levels were 0.47 ± 0.20 μg/g and 111.09 ± 55.01 μg/L for the two study populations, respectively. For both of the independent studies, higher Se levels were observed to be associated with a higher risk of diabetes and prediabetes. Compared with the Second nail Se quartile (Q2), the adjusted hazard ratios (HRs) and 95 % confidence intervals (95 % CIs) of diabetes for Q1, Q3 and Q4 were 1.24(0.70, 2.21), 1.53(0.98, 2.39) and 1.31(0.76, 2.26), respectively, and the adjusted HRs (95 % CIs) of prediabetes were 1.47(0.77, 2.81), 1.38(0.83, 2.30), and 1.97(1.13, 3.44), respectively. Compared with the first serum Se quintile (Q1), the adjusted odds ratios (ORs) and 95 % CIs of diabetes for higher quintiles were 1.12(0.75, 1.66), 1.05(0.71, 1.57), 1.09(0.73, 1.62) and 1.51(1.02, 2.19), and the adjusted ORs (95 % CIs) of prediabetes were 1.27(0.77, 2.09), 1.70(1.05, 2.74), 1.94(1.21, 3.11) and 1.67(1.03, 2.71). Our findings consistently suggest that higher Se status is associated with a higher risk of diabetes in adults.Item The p21-activated kinase (PAK1) is involved in diet-induced beta cell mass expansion and survival in mice and human islets(Springer, 2016-10) Ahn, Miwon; Yoder, Stephanie M.; Wang, Zhanxiang; Oh, Eunjin; Ramalingam, Latha; Tunduguru, Ragadeepthi; Thurmond, Debbie C.; Department of Pediatrics, IU School of MedicineAIMS/HYPOTHESIS: Human islets from type 2 diabetic donors are reportedly 80% deficient in the p21 (Cdc42/Rac)-activated kinase, PAK1. PAK1 is implicated in beta cell function and maintenance of beta cell mass. We questioned the mechanism(s) by which PAK1 deficiency potentially contributes to increased susceptibility to type 2 diabetes. METHODS: Non-diabetic human islets and INS 832/13 beta cells cultured under diabetogenic conditions (i.e. with specific cytokines or under glucolipotoxic [GLT] conditions) were evaluated for changes to PAK1 signalling. Combined effects of PAK1 deficiency with GLT stress were assessed using classic knockout (Pak1 (-/-) ) mice fed a 45% energy from fat/palmitate-based, 'western' diet (WD). INS 832/13 cells overexpressing or depleted of PAK1 were also assessed for apoptosis and signalling changes. RESULTS: Exposure of non-diabetic human islets to diabetic stressors attenuated PAK1 protein levels, concurrent with increased caspase 3 cleavage. WD-fed Pak1 knockout mice exhibited fasting hyperglycaemia and severe glucose intolerance. These mice also failed to mount an insulin secretory response following acute glucose challenge, coinciding with a 43% loss of beta cell mass when compared with WD-fed wild-type mice. Pak1 knockout mice had fewer total beta cells per islet, coincident with decreased beta cell proliferation. In INS 832/13 beta cells, PAK1 deficiency combined with GLT exposure heightened beta cell death relative to either condition alone; PAK1 deficiency resulted in decreased extracellular signal-related kinase (ERK) and B cell lymphoma 2 (Bcl2) phosphorylation levels. Conversely, PAK1 overexpression prevented GLT-induced cell death. CONCLUSIONS/INTERPRETATION: These findings suggest that PAK1 deficiency may underlie an increased diabetic susceptibility. Discovery of ways to remediate glycaemic dysregulation via altering PAK1 or its downstream effectors offers promising opportunities for disease intervention.Item Predictors of glycemic worsening in the next year in adults with screen-detected type 2 diabetes(medRxiv, 2024-04-27) Schneider Aguirre, Rebecca; Hannon, Tamara S.; Considine, Robert V.; Patel, Yash; Kirkman, M. Sue; Mather, Kieren J.; Pediatrics, School of MedicineBackground and aims: Identifying simple markers of risk for worsening glucose can allow care providers to target therapeutic interventions according to risk of worsening glycemic control. We aimed to determine which routine clinical measures herald near-term glycemic worsening in early type 2 diabetes(T2D). Methods: The Early Diabetes Intervention Program (EDIP) was a clinical trial in individuals with screendetected T2D [HbA1C 6.3+0.63%(45+5mmol/mol)]. During the trial some participants experienced worsening fasting blood glucose (FBG). We investigated the time course of FBG, HbA1c, weight, and other clinical factors to determine which might herald glycemic worsening over the next year. Results: Progressors (62/219, 28.5%) had higher FBG than non-progressors at baseline [118 vs 130mg/dL (6.6 vs 7.2 mmol/L), p=<0.001]. FBG was stable except in the year of progression, when progressors exhibited a large 1-year rise [mean change 14.2mg/dL(0.79 mmol/L)]. Current FBG and antecedent year change in FBG were associated with progression(p<0.01), although the magnitude of change was too small to be of clinical utility (0.19 mg/dL; 0.01 mmol/L). Current or antecedent year change in HbA1c, weight, TG or HDL were not associated with progression. In the year of glycemic worsening, rising glucose was strongly associated with a concurrent increase in weight (p<0.001). Conclusions: Elevated FBG but not HbA1c identified individuals at risk for imminent glycemic worsening; the subsequent large rise in glucose was associated with a short-term increase in weight. Glucose and weight surveillance provide actionable information for those caring for patients with early diabetes.Item β-Cell Function and Insulin Sensitivity in Youth With Early Type 1 Diabetes From a 2-Hour 7-Sample OGTT(The Endocrine Society, 2023) Galderisi, Alfonso; Evans-Molina, Carmella; Martino, Mariangela; Caprio, Sonia; Cobelli, Claudio; Moran, Antoinette; Pediatrics, School of MedicineContext: The oral minimal model is a widely accepted noninvasive tool to quantify both β-cell responsiveness and insulin sensitivity (SI) from glucose, C-peptide, and insulin concentrations during a 3-hour 9-point oral glucose tolerance test (OGTT). Objective: Here, we aimed to validate a 2-hour 7-point protocol against the 3-hour OGTT and to test how variation in early sampling frequency impacts estimates of β-cell responsiveness and SI. Methods: We conducted a secondary analysis on 15 lean youth with stage 1 type 1 diabetes (T1D; ≥ 2 islet autoantibodies with no dysglycemia) who underwent a 3-hour 9-point OGTT. The oral minimal model was used to quantitate β-cell responsiveness (φtotal) and insulin sensitivity (SI), allowing assessment of β-cell function by the disposition index (DI = φtotal × SI). Seven- and 5-point 2-hour OGTT protocols were tested against the 3-hour 9-point gold standard to determine agreement between estimates of φtotal and its dynamic and static components, SI, and DI across different sampling strategies. Results: The 2-hour estimates for the disposition index exhibited a strong correlation with 3-hour measures (r = 0.975; P < .001) with similar results for β-cell responsiveness and SI (r = 0.997 and r = 0.982; P < .001, respectively). The agreement of the 3 estimates between the 7-point 2-hour and 9-point 3-hour protocols fell within the 95% CI on the Bland-Altman grid with a median difference of 16.9% (-35.3 to 32.5), 0.2% (-0.6 to 1.3), and 14.9% (-1.4 to 28.3) for DI, φtotal, and SI. Conversely, the 5-point protocol did not provide reliable estimates of φ dynamic and static components. Conclusion: The 2-hour 7-point OGTT is reliable in individuals with stage 1 T1D for assessment of β-cell responsiveness, SI, and DI. Incorporation of these analyses into current 2-hour diabetes staging and monitoring OGTTs offers the potential to more accurately quantify risk of progression in the early stages of T1D.