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Fida Bacha - One of the best experts on this subject based on the ideXlab platform.

  • heart rate variability and cardiac autonomic dysfunction prevalence risk factors and relationship to arterial stiffness in the treatment options for type 2 Diabetes in Adolescents and youth today study
    Diabetes Care, 2019
    Co-Authors: Amy S Shah, Laure El Ghormli, Fida Bacha, Neil H White, Mary Ellen Vajravelu, Ryan M Farrell, Samuel S Gidding, Lorraine Levitt E Katz, Jeanie B Tryggestad, Elaine M Urbina
    Abstract:

    OBJECTIVE To determine whether prior type 2 Diabetes (T2D) treatment or glycemic control over time are independently associated with heart rate variability (HRV) and whether the presence of cardiac autonomic dysfunction is associated with arterial stiffness in young adults with youth-onset T2D enrolled in the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study. RESEARCH DESIGN AND METHODS Heartbeats over 10 min were measured to derive the normal R-Rs (NN intervals). Outcomes included the standard deviation of the NN intervals (SDNN), the root mean square differences of successive NN intervals (RMSSD), percent of NN beats that differ by more than 50 ms (PNN50), and the low-frequency (LF) power domain, high-frequency (HF) power domain, and their ratio (LF:HF). Autonomic dysfunction was defined as ≥3 of 5 abnormal HRV indices compared with obese controls from a separate study. RESULTS A total of 397 TODAY participants were evaluated 7 years after randomization. TODAY participants had reduced HRV (SDNN; 57.9 ± 29.6 ms vs. controls 67.1 ± 25.4 ms; P CONCLUSIONS Young adults with youth-onset T2D show evidence of cardiac autonomic dysfunction with both parasympathetic and sympathetic impairments that are associated with higher HbA1c.

  • the shape of the glucose response curve during an oral glucose tolerance test forerunner of heightened glycemic failure rates and accelerated decline in β cell function in today
    Diabetes Care, 2019
    Co-Authors: Silva A Arslanian, Laure El Ghormli, Fida Bacha, Lynne L Levitsky, Lorraine Levitt E Katz, Jeanie B Tryggestad, Christine Chan, Heba M Ismail, Neil H White
    Abstract:

    OBJECTIVE Obese youth without Diabetes with monophasic oral glucose tolerance test (OGTT) glucose-response curves have lower insulin sensitivity (IS) and impaired β-cell function compared with those with biphasic curves. The OGTT glucose response curve has not been studied in youth-onset type 2 Diabetes. Here we test the hypothesis that the OGTT glucose response curve at randomization in youth in the TODAY (Treatment Options for Type 2 Diabetes in Adolescents and Youth) study forecasts heightened glycemic failure rates and accelerated decline in β-cell function. RESEARCH DESIGN AND METHODS OGTTs ( n = 662) performed at randomization were categorized as monophasic, biphasic, or incessant increase. Demographics, IS (1/fasting insulin), C-peptide index (△C 30 /△G 30 ), and β-cell function relative to IS (oral disposition index [oDI]) were compared among the three groups. RESULTS At randomization, 21.7% had incessant increase, 68.6% monophasic, and 9.7% biphasic glucose response curves. The incessant increase group had similar IS, but significantly lower C-peptide index and lower oDI, despite similar Diabetes duration, compared with the other two groups. Glycemic failure rates were higher in the incessant increase group (58.3%) versus the monophasic group (42.3%) versus biphasic group (39.1%) ( P CONCLUSIONS in the TODAY study cohort, an incessant increase in the OGTT glucose response curve at randomization reflects reduced β-cell function and foretells increased glycemic failure rates with accelerated deterioration in β-cell function independent of Diabetes duration and treatment assignment compared with monophasic and biphasic curves. The shape of the OGTT glucose response curve could be a metabolic biomarker prognosticating the response to therapy in youth with type 2 Diabetes.

  • lipid profiles inflammatory markers and insulin therapy in youth with type 2 Diabetes
    The Journal of Pediatrics, 2018
    Co-Authors: Lorraine Levitt E Katz, Laure El Ghormli, Fida Bacha, Kristen J Nadeau, Samuel S Gidding, Ruth S Weinstock, Ingrid Libman, Kristin Porter, Santica M Marcovina, Siripoom Mckay
    Abstract:

    Objectives Data regarding atherogenic dyslipidemia and the inflammation profile in youth with type 2 Diabetes is limited and the effect of insulin therapy on these variables has not previously been studied in youth. We determined the impact of insulin therapy on lipid and inflammatory markers in youth with poorly controlled type 2 Diabetes. Study design in the Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY) multicenter trial, 285 participants failed to sustain glycemic control on randomized treatment (primary outcome, glycated hemoglobin A1c [HbA1c] at ≥8% for 6 months); 363 maintained glycemic control (never reached primary outcome). Statins were used for a low-density lipoprotein cholesterol of ≥130 mg/dL. Upon reaching the primary outcome, insulin was started. Changes in lipids and inflammatory markers (slopes over time) were examined. Results Progression of dyslipidemia was related to glycemic control. in those with the primary outcome, insulin therapy impacted HbA1c modestly, and dampened the increase in total cholesterol, low-density lipoprotein cholesterol, and total apolipoprotein B, although statin use increased from 8.6% to 22% year after the primary outcome. The increase in triglycerides and plasma nonesterified fatty acids stabilized after insulin was started, independent of HbA1c. There was an increase in high-sensitivity C-reactive protein that continued after insulin initiation, related to HbA1c and percent overweight. Conclusions Worsening dyslipidemia and inflammation over time raise concern regarding premature development of atherosclerosis in youth with type 2 Diabetes. insulin therapy has a limited benefit in the absence of glycemic control. Strategies to achieve better glycemic control are needed. Trial registration ClinicalTrials.gov : NCT00081328 .

  • adiponectin insulin sensitivity β cell function and racial ethnic disparity in treatment failure rates in today
    Diabetes Care, 2017
    Co-Authors: Silva A Arslanian, Laure El Ghormli, Fida Bacha, Sonia Caprio, Robin Goland, Morey W Haymond, Lynne L Levitsky, Kristen J Nadeau, Neil H White, Steven M Willi
    Abstract:

    OBJECTIVE The Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY) study demonstrated that glycemic failure rates in the three treatments combined—metformin plus rosiglitazone, metformin alone, and metformin plus lifestyle—were higher in non-Hispanic blacks (NHB; 52.8%) versus non-Hispanic whites (NHW; 36.6%) and Hispanics (H; 45.0%). Moreover, metformin alone was less effective in NHB versus NHW versus H youth. This study describes treatment-associated changes in adiponectin, insulin sensitivity, and β-cell function over time among the three racial/ethnic groups to understand potential mechanism(s) responsible for this racial/ethnic disparity. RESEARCH DESIGN AND METHODS TODAY participants underwent periodic oral glucose tolerance tests to determine insulin sensitivity, C-peptide index, and oral disposition index (oDI), with measurements of total and high-molecular-weight adiponectin (HMWA). RESULTS At baseline NHB had significantly lower HMWA than NHW and H and exhibited a significantly smaller increase (17.3% vs. 33.7% vs. 29.9%, respectively) during the first 6 months overall. increases in HMWA were associated with reductions in glycemic failure in the three racial/ethnic groups combined (hazard ratio 0.61, P CONCLUSIONS HMWA is a reliable biomarker of treatment response in youth with type 2 Diabetes. The diminutive treatment-associated increase in HMWA in NHB (∼50% lower) compared with NHW and H may explain the observed racial/ethnic disparity with higher therapeutic failure rates in NHB in TODAY.

  • relationship of cardiac structure and function to cardiorespiratory fitness and lean body mass in Adolescents and young adults with type 2 Diabetes
    The Journal of Pediatrics, 2016
    Co-Authors: Fida Bacha, Kristen J Nadeau, Laura Pyle, Samuel S Gidding, Lorraine Levitt E Katz, Andrea M Kriska, Joao A C Lima, Treatment Options For Type Diabetes In Adolescents
    Abstract:

    Objective To investigate the relationships of cardiac structure and function with body composition and cardiorespiratory fitness (CRF) among Adolescents with type 2 Diabetes in the Treatment Options for Type 2 Diabetes in Adolescents and Youth study. Study design Cross-sectional evaluation of 233 participants (median age 18.3 [min-max 12.4-24.2] years, 63% females, median hemoglobin A1c 6.8%) who had echocardiography measurements of left ventricular (LV) mass, ejection fraction, left atrial dimensions, LV diastolic function (early transmitral flow velocity to early mitral annular velocity ratio from tissue Doppler imaging), and right ventricular function (tricuspid annular plane systolic excursion [TAPSE]) and body composition (dual-energy x-ray absorptiometry) and CRF (cycle ergometry determination of physical work capacity at heart rate of 170 beats per minute). Results LV mass correlated positively with CRF (r = 0.5, P  Conclusions in youth with type 2 Diabetes, LV size is related to physical fitness. LV ejection fraction is within normal limits. LV diastolic function is inversely related to FM. Greater fitness may counteract adverse effects of poor glycemic control on right ventricular function. Trial registration ClinicalTrials.gov: NCT00081328

Laure El Ghormli - One of the best experts on this subject based on the ideXlab platform.

  • beta cell function and insulin sensitivity in obese youth with maturity onset Diabetes of youth mutations vs type 2 Diabetes in today longitudinal observations and glycemic failure
    Pediatric Diabetes, 2020
    Co-Authors: Silva A Arslanian, Laure El Ghormli, Morey W Haymond, Lynne L Levitsky, Christine L Chan, Steven D Chernausek, Rachelle Gandica, Rose A Gubitosiklug, Maggie Siska, Steven M Willi
    Abstract:

    OBJECTIVE in treatment options for type 2 Diabetes in Adolescents and youth (TODAY), 4.5% of obese youth clinically diagnosed with type 2 Diabetes (T2D) had genetic variants consistent with maturity onset Diabetes of youth (MODY) diagnosis. The course of IS and β-cell function in obese youth with MODY remains unknown. in this secondary analysis, we examined IS and β-cell function in MODY vs. non-MODY obese youth at randomization and over time. METHODS Genetic data in TODAY included 426 non-MODY (T2D) and 22 MODY youth (7 glucokinase MODY mutation positive [GCK-MODY], 12 hepatocyte nuclear factor MODY mutation positive [HNF-MODY], 2 insulin gene mutation [insulin (inS)-MODY], and 1 Kruppel-like factor 11 [KLF11-MODY]). Oral glucose tolerance test (OGTT)-derived IS, C-peptide index, and β-cell function relative to IS oral disposition index (oDI) was measured at randomization, and over 24 months in addition to total and high-molecular-weight adiponectin (HMWA). RESULTS At randomization, IS, total adiponectin, and HMWA were significantly higher in the two MODY groups than in non-MODY. β-cell function measured by C-peptide oDI was 3-fold higher in GCK-MODY than in HNF-MODY and 1.5-fold higher than non-MODY (P for both <.05). Glycemic failure rate was 75.0% in HNF-MODY, 46.9% in non-MODY, and zero in GCK-MODY youth. While the changes in IS and oDI were not different among the three groups in the first 6 months, IS improved from 6 to 24 months in HNF-MODY vs GCK-MODY youth. CONCLUSIONS in TODAY, β-cell function at randomization was worse in obese HNF-MODY youth compared with GCK-MODY youth, while insulin sensitivity was worse in non-MODY compared with the other two MODY groups. Over time, IS showed the greatest improvement in HNF-MODY youth. This raises the possibility that TODAY therapeutic modalities of insulin sensitization in these obese HNF-MODY youth may have played a beneficial role.

  • heart rate variability and cardiac autonomic dysfunction prevalence risk factors and relationship to arterial stiffness in the treatment options for type 2 Diabetes in Adolescents and youth today study
    Diabetes Care, 2019
    Co-Authors: Amy S Shah, Laure El Ghormli, Fida Bacha, Neil H White, Mary Ellen Vajravelu, Ryan M Farrell, Samuel S Gidding, Lorraine Levitt E Katz, Jeanie B Tryggestad, Elaine M Urbina
    Abstract:

    OBJECTIVE To determine whether prior type 2 Diabetes (T2D) treatment or glycemic control over time are independently associated with heart rate variability (HRV) and whether the presence of cardiac autonomic dysfunction is associated with arterial stiffness in young adults with youth-onset T2D enrolled in the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study. RESEARCH DESIGN AND METHODS Heartbeats over 10 min were measured to derive the normal R-Rs (NN intervals). Outcomes included the standard deviation of the NN intervals (SDNN), the root mean square differences of successive NN intervals (RMSSD), percent of NN beats that differ by more than 50 ms (PNN50), and the low-frequency (LF) power domain, high-frequency (HF) power domain, and their ratio (LF:HF). Autonomic dysfunction was defined as ≥3 of 5 abnormal HRV indices compared with obese controls from a separate study. RESULTS A total of 397 TODAY participants were evaluated 7 years after randomization. TODAY participants had reduced HRV (SDNN; 57.9 ± 29.6 ms vs. controls 67.1 ± 25.4 ms; P CONCLUSIONS Young adults with youth-onset T2D show evidence of cardiac autonomic dysfunction with both parasympathetic and sympathetic impairments that are associated with higher HbA1c.

  • elevated serum uric acid is associated with greater risk for hypertension and diabetic kidney diseases in obese Adolescents with type 2 Diabetes an observational analysis from the treatment options for type 2 Diabetes in Adolescents and youth today study
    Diabetes Care, 2019
    Co-Authors: Petter Bjornstad, Laure El Ghormli, Lori M Laffel, Ruth S Weinstock, Jane L Lynch, Sherida E Tollefsen, Kristen J Nadeau
    Abstract:

    OBJECTIVE Elevated serum uric acid (SUA) is increasingly recognized as a risk factor for kidney disease in adults with Diabetes, but data in youth are limited. We hypothesized that elevated SUA predicts development of elevated urinary albumin excretion (UAE) and hypertension over time in teens with type 2 Diabetes (T2D). RESEARCH DESIGN AND METHODS Serum creatinine, cystatin C, SUA, and the urine albumin-to-creatinine ratio (UACR) were assessed in 539 obese youth, ages 12–17 years, with T2D duration 1c , eGFR, ACE inhibitor/angiotensin receptor blocker use, and TODAY treatment group assignment. RESULTS At baseline, hyperuricemia (≥6.8 mg/dL) was present in 25.6% of participants, hypertension in 18.7%, and elevated UAE in 6.1%. During follow-up of up to 7 years, hypertension developed in 37.4% and UAE in 18.0%. Higher baseline SUA increased the risk of incident hypertension (hazard ratio [HR] 1.19, 95% CI 1.03–1.38, per 1 mg/dL increase in SUA) and elevated UAE (HR 1.24, 95% CI 1.03–1.48) in adjusted models. CONCLUSIONS Hyperuricemia was common in youth with T2D. Higher baseline SUA independently increased the risk for onset of hypertension and elevated UAE. Research is needed to determine whether SUA-lowering therapies can impede development of diabetic kidney disease and hypertension in T2D youth.

  • the shape of the glucose response curve during an oral glucose tolerance test forerunner of heightened glycemic failure rates and accelerated decline in β cell function in today
    Diabetes Care, 2019
    Co-Authors: Silva A Arslanian, Laure El Ghormli, Fida Bacha, Lynne L Levitsky, Lorraine Levitt E Katz, Jeanie B Tryggestad, Christine Chan, Heba M Ismail, Neil H White
    Abstract:

    OBJECTIVE Obese youth without Diabetes with monophasic oral glucose tolerance test (OGTT) glucose-response curves have lower insulin sensitivity (IS) and impaired β-cell function compared with those with biphasic curves. The OGTT glucose response curve has not been studied in youth-onset type 2 Diabetes. Here we test the hypothesis that the OGTT glucose response curve at randomization in youth in the TODAY (Treatment Options for Type 2 Diabetes in Adolescents and Youth) study forecasts heightened glycemic failure rates and accelerated decline in β-cell function. RESEARCH DESIGN AND METHODS OGTTs ( n = 662) performed at randomization were categorized as monophasic, biphasic, or incessant increase. Demographics, IS (1/fasting insulin), C-peptide index (△C 30 /△G 30 ), and β-cell function relative to IS (oral disposition index [oDI]) were compared among the three groups. RESULTS At randomization, 21.7% had incessant increase, 68.6% monophasic, and 9.7% biphasic glucose response curves. The incessant increase group had similar IS, but significantly lower C-peptide index and lower oDI, despite similar Diabetes duration, compared with the other two groups. Glycemic failure rates were higher in the incessant increase group (58.3%) versus the monophasic group (42.3%) versus biphasic group (39.1%) ( P CONCLUSIONS in the TODAY study cohort, an incessant increase in the OGTT glucose response curve at randomization reflects reduced β-cell function and foretells increased glycemic failure rates with accelerated deterioration in β-cell function independent of Diabetes duration and treatment assignment compared with monophasic and biphasic curves. The shape of the OGTT glucose response curve could be a metabolic biomarker prognosticating the response to therapy in youth with type 2 Diabetes.

  • lipid profiles inflammatory markers and insulin therapy in youth with type 2 Diabetes
    The Journal of Pediatrics, 2018
    Co-Authors: Lorraine Levitt E Katz, Laure El Ghormli, Fida Bacha, Kristen J Nadeau, Samuel S Gidding, Ruth S Weinstock, Ingrid Libman, Kristin Porter, Santica M Marcovina, Siripoom Mckay
    Abstract:

    Objectives Data regarding atherogenic dyslipidemia and the inflammation profile in youth with type 2 Diabetes is limited and the effect of insulin therapy on these variables has not previously been studied in youth. We determined the impact of insulin therapy on lipid and inflammatory markers in youth with poorly controlled type 2 Diabetes. Study design in the Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY) multicenter trial, 285 participants failed to sustain glycemic control on randomized treatment (primary outcome, glycated hemoglobin A1c [HbA1c] at ≥8% for 6 months); 363 maintained glycemic control (never reached primary outcome). Statins were used for a low-density lipoprotein cholesterol of ≥130 mg/dL. Upon reaching the primary outcome, insulin was started. Changes in lipids and inflammatory markers (slopes over time) were examined. Results Progression of dyslipidemia was related to glycemic control. in those with the primary outcome, insulin therapy impacted HbA1c modestly, and dampened the increase in total cholesterol, low-density lipoprotein cholesterol, and total apolipoprotein B, although statin use increased from 8.6% to 22% year after the primary outcome. The increase in triglycerides and plasma nonesterified fatty acids stabilized after insulin was started, independent of HbA1c. There was an increase in high-sensitivity C-reactive protein that continued after insulin initiation, related to HbA1c and percent overweight. Conclusions Worsening dyslipidemia and inflammation over time raise concern regarding premature development of atherosclerosis in youth with type 2 Diabetes. insulin therapy has a limited benefit in the absence of glycemic control. Strategies to achieve better glycemic control are needed. Trial registration ClinicalTrials.gov : NCT00081328 .

Lorraine Levitt E Katz - One of the best experts on this subject based on the ideXlab platform.

  • heart rate variability and cardiac autonomic dysfunction prevalence risk factors and relationship to arterial stiffness in the treatment options for type 2 Diabetes in Adolescents and youth today study
    Diabetes Care, 2019
    Co-Authors: Amy S Shah, Laure El Ghormli, Fida Bacha, Neil H White, Mary Ellen Vajravelu, Ryan M Farrell, Samuel S Gidding, Lorraine Levitt E Katz, Jeanie B Tryggestad, Elaine M Urbina
    Abstract:

    OBJECTIVE To determine whether prior type 2 Diabetes (T2D) treatment or glycemic control over time are independently associated with heart rate variability (HRV) and whether the presence of cardiac autonomic dysfunction is associated with arterial stiffness in young adults with youth-onset T2D enrolled in the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study. RESEARCH DESIGN AND METHODS Heartbeats over 10 min were measured to derive the normal R-Rs (NN intervals). Outcomes included the standard deviation of the NN intervals (SDNN), the root mean square differences of successive NN intervals (RMSSD), percent of NN beats that differ by more than 50 ms (PNN50), and the low-frequency (LF) power domain, high-frequency (HF) power domain, and their ratio (LF:HF). Autonomic dysfunction was defined as ≥3 of 5 abnormal HRV indices compared with obese controls from a separate study. RESULTS A total of 397 TODAY participants were evaluated 7 years after randomization. TODAY participants had reduced HRV (SDNN; 57.9 ± 29.6 ms vs. controls 67.1 ± 25.4 ms; P CONCLUSIONS Young adults with youth-onset T2D show evidence of cardiac autonomic dysfunction with both parasympathetic and sympathetic impairments that are associated with higher HbA1c.

  • the shape of the glucose response curve during an oral glucose tolerance test forerunner of heightened glycemic failure rates and accelerated decline in β cell function in today
    Diabetes Care, 2019
    Co-Authors: Silva A Arslanian, Laure El Ghormli, Fida Bacha, Lynne L Levitsky, Lorraine Levitt E Katz, Jeanie B Tryggestad, Christine Chan, Heba M Ismail, Neil H White
    Abstract:

    OBJECTIVE Obese youth without Diabetes with monophasic oral glucose tolerance test (OGTT) glucose-response curves have lower insulin sensitivity (IS) and impaired β-cell function compared with those with biphasic curves. The OGTT glucose response curve has not been studied in youth-onset type 2 Diabetes. Here we test the hypothesis that the OGTT glucose response curve at randomization in youth in the TODAY (Treatment Options for Type 2 Diabetes in Adolescents and Youth) study forecasts heightened glycemic failure rates and accelerated decline in β-cell function. RESEARCH DESIGN AND METHODS OGTTs ( n = 662) performed at randomization were categorized as monophasic, biphasic, or incessant increase. Demographics, IS (1/fasting insulin), C-peptide index (△C 30 /△G 30 ), and β-cell function relative to IS (oral disposition index [oDI]) were compared among the three groups. RESULTS At randomization, 21.7% had incessant increase, 68.6% monophasic, and 9.7% biphasic glucose response curves. The incessant increase group had similar IS, but significantly lower C-peptide index and lower oDI, despite similar Diabetes duration, compared with the other two groups. Glycemic failure rates were higher in the incessant increase group (58.3%) versus the monophasic group (42.3%) versus biphasic group (39.1%) ( P CONCLUSIONS in the TODAY study cohort, an incessant increase in the OGTT glucose response curve at randomization reflects reduced β-cell function and foretells increased glycemic failure rates with accelerated deterioration in β-cell function independent of Diabetes duration and treatment assignment compared with monophasic and biphasic curves. The shape of the OGTT glucose response curve could be a metabolic biomarker prognosticating the response to therapy in youth with type 2 Diabetes.

  • lipid profiles inflammatory markers and insulin therapy in youth with type 2 Diabetes
    The Journal of Pediatrics, 2018
    Co-Authors: Lorraine Levitt E Katz, Laure El Ghormli, Fida Bacha, Kristen J Nadeau, Samuel S Gidding, Ruth S Weinstock, Ingrid Libman, Kristin Porter, Santica M Marcovina, Siripoom Mckay
    Abstract:

    Objectives Data regarding atherogenic dyslipidemia and the inflammation profile in youth with type 2 Diabetes is limited and the effect of insulin therapy on these variables has not previously been studied in youth. We determined the impact of insulin therapy on lipid and inflammatory markers in youth with poorly controlled type 2 Diabetes. Study design in the Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY) multicenter trial, 285 participants failed to sustain glycemic control on randomized treatment (primary outcome, glycated hemoglobin A1c [HbA1c] at ≥8% for 6 months); 363 maintained glycemic control (never reached primary outcome). Statins were used for a low-density lipoprotein cholesterol of ≥130 mg/dL. Upon reaching the primary outcome, insulin was started. Changes in lipids and inflammatory markers (slopes over time) were examined. Results Progression of dyslipidemia was related to glycemic control. in those with the primary outcome, insulin therapy impacted HbA1c modestly, and dampened the increase in total cholesterol, low-density lipoprotein cholesterol, and total apolipoprotein B, although statin use increased from 8.6% to 22% year after the primary outcome. The increase in triglycerides and plasma nonesterified fatty acids stabilized after insulin was started, independent of HbA1c. There was an increase in high-sensitivity C-reactive protein that continued after insulin initiation, related to HbA1c and percent overweight. Conclusions Worsening dyslipidemia and inflammation over time raise concern regarding premature development of atherosclerosis in youth with type 2 Diabetes. insulin therapy has a limited benefit in the absence of glycemic control. Strategies to achieve better glycemic control are needed. Trial registration ClinicalTrials.gov : NCT00081328 .

  • relationship of cardiac structure and function to cardiorespiratory fitness and lean body mass in Adolescents and young adults with type 2 Diabetes
    The Journal of Pediatrics, 2016
    Co-Authors: Fida Bacha, Kristen J Nadeau, Laura Pyle, Samuel S Gidding, Lorraine Levitt E Katz, Andrea M Kriska, Joao A C Lima, Treatment Options For Type Diabetes In Adolescents
    Abstract:

    Objective To investigate the relationships of cardiac structure and function with body composition and cardiorespiratory fitness (CRF) among Adolescents with type 2 Diabetes in the Treatment Options for Type 2 Diabetes in Adolescents and Youth study. Study design Cross-sectional evaluation of 233 participants (median age 18.3 [min-max 12.4-24.2] years, 63% females, median hemoglobin A1c 6.8%) who had echocardiography measurements of left ventricular (LV) mass, ejection fraction, left atrial dimensions, LV diastolic function (early transmitral flow velocity to early mitral annular velocity ratio from tissue Doppler imaging), and right ventricular function (tricuspid annular plane systolic excursion [TAPSE]) and body composition (dual-energy x-ray absorptiometry) and CRF (cycle ergometry determination of physical work capacity at heart rate of 170 beats per minute). Results LV mass correlated positively with CRF (r = 0.5, P  Conclusions in youth with type 2 Diabetes, LV size is related to physical fitness. LV ejection fraction is within normal limits. LV diastolic function is inversely related to FM. Greater fitness may counteract adverse effects of poor glycemic control on right ventricular function. Trial registration ClinicalTrials.gov: NCT00081328

  • alterations in left ventricular left atrial and right ventricular structure and function to cardiovascular risk factors in Adolescents with type 2 Diabetes participating in the today clinical trial
    Pediatric Diabetes, 2015
    Co-Authors: Lorraine Levitt E Katz, Fida Bacha, Laura Pyle, Samuel S Gidding, Kathryn Hirst, Siripoom Mckay, Joao A C Lima
    Abstract:

    Data on cardiovascular disease (CVD) risk in Adolescents with type 2 Diabetes (T2D) are limited. Echocardiography was performed in the last year of the Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY) clinical trial (median 4½ yr from diagnosis of T2D, average age 18 yr), including MMode and 2D measurements of left ventricular (LV) and left atrial (LA) dimensions, LV tissue Doppler imaging (TDI), and tricuspid annular plane systolic excursion (TAPSE). Relationships between cardiac structure and function with demographic characteristics and baseline and change-from-baseline in CVD risk factors were examined in 455 participants. Mean LV mass (LVM) was high/normal and 16.2% had adverse LV geometry (8.1% concentric geometry, 4.5% LV hypertrophy, and 3.6% both). Determinants of higher LVM were male gender, black race, baseline and increasing body mass index (BMI), baseline and increasing systolic blood pressure (SBP), use of blood pressure (BP) medications, maintenance of glycemic control, and smoking; heart rate (HR) was inversely related. LV shortening fraction was high/normal and related to increasing BMI and higher baseline SBP. LV relative wall thickness was related to race-ethnicity, change in BMI, baseline glycated hemoglobin (HbA1c), and baseline and change in SBP. Mean LA internal dimension was high/normal and gender, baseline and increasing BMI, increasing SBP, and HR (inverse) were related. LV TDI was positively related to obesity (higher with adverse geometry). TAPSE was normal and related to higher baseline BMI and lower HR. There was no effect of T2D treatment on cardiac target organ injury. Adolescents with T2D have adverse measures of cardiac structure and function positively related to BMI and BP.

Kathryn Hirst - One of the best experts on this subject based on the ideXlab platform.

  • benefits and barriers to participating in longitudinal research of youth onset type 2 Diabetes results from the today retention survey
    Clinical Trials, 2016
    Co-Authors: Natalie Waldersabramson, Elizabeth M Venditti, Jeanie B Tryggestad, Barbara J Anderson, Mary E Larkin, N Chang, Suzan Bzdick, Mitchell E Geffner, Kathryn Hirst
    Abstract:

    Background/Aims:Conducting longitudinal research related to chronic illness in Adolescents is inherently challenging due to developmental changes and psychosocial stressors. Participants in the Treatment Options for type 2 Diabetes in Adolescents and Youth clinical trial were socioeconomically disadvantaged as well. This study assessed attitudes and beliefs about retention in Treatment Options for type 2 Diabetes in Adolescents and Youth to shed light on the factors that potentially promote and detract from the likelihood of sustained participation.Methods:After an average 7.3 years of follow-up (range 4.9–9.5), Treatment Options for type 2 Diabetes in Adolescents and Youth participants completed a survey examining their perceptions of the benefits and barriers to sustained involvement in the protocol.Results:The most common reasons for staying in Treatment Options for type 2 Diabetes in Adolescents and Youth included having a strong relationship with the medical team, getting study-provided Diabetes care...

  • alterations in left ventricular left atrial and right ventricular structure and function to cardiovascular risk factors in Adolescents with type 2 Diabetes participating in the today clinical trial
    Pediatric Diabetes, 2015
    Co-Authors: Lorraine Levitt E Katz, Fida Bacha, Laura Pyle, Samuel S Gidding, Kathryn Hirst, Siripoom Mckay, Joao A C Lima
    Abstract:

    Data on cardiovascular disease (CVD) risk in Adolescents with type 2 Diabetes (T2D) are limited. Echocardiography was performed in the last year of the Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY) clinical trial (median 4½ yr from diagnosis of T2D, average age 18 yr), including MMode and 2D measurements of left ventricular (LV) and left atrial (LA) dimensions, LV tissue Doppler imaging (TDI), and tricuspid annular plane systolic excursion (TAPSE). Relationships between cardiac structure and function with demographic characteristics and baseline and change-from-baseline in CVD risk factors were examined in 455 participants. Mean LV mass (LVM) was high/normal and 16.2% had adverse LV geometry (8.1% concentric geometry, 4.5% LV hypertrophy, and 3.6% both). Determinants of higher LVM were male gender, black race, baseline and increasing body mass index (BMI), baseline and increasing systolic blood pressure (SBP), use of blood pressure (BP) medications, maintenance of glycemic control, and smoking; heart rate (HR) was inversely related. LV shortening fraction was high/normal and related to increasing BMI and higher baseline SBP. LV relative wall thickness was related to race-ethnicity, change in BMI, baseline glycated hemoglobin (HbA1c), and baseline and change in SBP. Mean LA internal dimension was high/normal and gender, baseline and increasing BMI, increasing SBP, and HR (inverse) were related. LV TDI was positively related to obesity (higher with adverse geometry). TAPSE was normal and related to higher baseline BMI and lower HR. There was no effect of T2D treatment on cardiac target organ injury. Adolescents with T2D have adverse measures of cardiac structure and function positively related to BMI and BP.

Silva A Arslanian - One of the best experts on this subject based on the ideXlab platform.

  • beta cell function and insulin sensitivity in obese youth with maturity onset Diabetes of youth mutations vs type 2 Diabetes in today longitudinal observations and glycemic failure
    Pediatric Diabetes, 2020
    Co-Authors: Silva A Arslanian, Laure El Ghormli, Morey W Haymond, Lynne L Levitsky, Christine L Chan, Steven D Chernausek, Rachelle Gandica, Rose A Gubitosiklug, Maggie Siska, Steven M Willi
    Abstract:

    OBJECTIVE in treatment options for type 2 Diabetes in Adolescents and youth (TODAY), 4.5% of obese youth clinically diagnosed with type 2 Diabetes (T2D) had genetic variants consistent with maturity onset Diabetes of youth (MODY) diagnosis. The course of IS and β-cell function in obese youth with MODY remains unknown. in this secondary analysis, we examined IS and β-cell function in MODY vs. non-MODY obese youth at randomization and over time. METHODS Genetic data in TODAY included 426 non-MODY (T2D) and 22 MODY youth (7 glucokinase MODY mutation positive [GCK-MODY], 12 hepatocyte nuclear factor MODY mutation positive [HNF-MODY], 2 insulin gene mutation [insulin (inS)-MODY], and 1 Kruppel-like factor 11 [KLF11-MODY]). Oral glucose tolerance test (OGTT)-derived IS, C-peptide index, and β-cell function relative to IS oral disposition index (oDI) was measured at randomization, and over 24 months in addition to total and high-molecular-weight adiponectin (HMWA). RESULTS At randomization, IS, total adiponectin, and HMWA were significantly higher in the two MODY groups than in non-MODY. β-cell function measured by C-peptide oDI was 3-fold higher in GCK-MODY than in HNF-MODY and 1.5-fold higher than non-MODY (P for both <.05). Glycemic failure rate was 75.0% in HNF-MODY, 46.9% in non-MODY, and zero in GCK-MODY youth. While the changes in IS and oDI were not different among the three groups in the first 6 months, IS improved from 6 to 24 months in HNF-MODY vs GCK-MODY youth. CONCLUSIONS in TODAY, β-cell function at randomization was worse in obese HNF-MODY youth compared with GCK-MODY youth, while insulin sensitivity was worse in non-MODY compared with the other two MODY groups. Over time, IS showed the greatest improvement in HNF-MODY youth. This raises the possibility that TODAY therapeutic modalities of insulin sensitization in these obese HNF-MODY youth may have played a beneficial role.

  • the shape of the glucose response curve during an oral glucose tolerance test forerunner of heightened glycemic failure rates and accelerated decline in β cell function in today
    Diabetes Care, 2019
    Co-Authors: Silva A Arslanian, Laure El Ghormli, Fida Bacha, Lynne L Levitsky, Lorraine Levitt E Katz, Jeanie B Tryggestad, Christine Chan, Heba M Ismail, Neil H White
    Abstract:

    OBJECTIVE Obese youth without Diabetes with monophasic oral glucose tolerance test (OGTT) glucose-response curves have lower insulin sensitivity (IS) and impaired β-cell function compared with those with biphasic curves. The OGTT glucose response curve has not been studied in youth-onset type 2 Diabetes. Here we test the hypothesis that the OGTT glucose response curve at randomization in youth in the TODAY (Treatment Options for Type 2 Diabetes in Adolescents and Youth) study forecasts heightened glycemic failure rates and accelerated decline in β-cell function. RESEARCH DESIGN AND METHODS OGTTs ( n = 662) performed at randomization were categorized as monophasic, biphasic, or incessant increase. Demographics, IS (1/fasting insulin), C-peptide index (△C 30 /△G 30 ), and β-cell function relative to IS (oral disposition index [oDI]) were compared among the three groups. RESULTS At randomization, 21.7% had incessant increase, 68.6% monophasic, and 9.7% biphasic glucose response curves. The incessant increase group had similar IS, but significantly lower C-peptide index and lower oDI, despite similar Diabetes duration, compared with the other two groups. Glycemic failure rates were higher in the incessant increase group (58.3%) versus the monophasic group (42.3%) versus biphasic group (39.1%) ( P CONCLUSIONS in the TODAY study cohort, an incessant increase in the OGTT glucose response curve at randomization reflects reduced β-cell function and foretells increased glycemic failure rates with accelerated deterioration in β-cell function independent of Diabetes duration and treatment assignment compared with monophasic and biphasic curves. The shape of the OGTT glucose response curve could be a metabolic biomarker prognosticating the response to therapy in youth with type 2 Diabetes.

  • adiponectin insulin sensitivity β cell function and racial ethnic disparity in treatment failure rates in today
    Diabetes Care, 2017
    Co-Authors: Silva A Arslanian, Laure El Ghormli, Fida Bacha, Sonia Caprio, Robin Goland, Morey W Haymond, Lynne L Levitsky, Kristen J Nadeau, Neil H White, Steven M Willi
    Abstract:

    OBJECTIVE The Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY) study demonstrated that glycemic failure rates in the three treatments combined—metformin plus rosiglitazone, metformin alone, and metformin plus lifestyle—were higher in non-Hispanic blacks (NHB; 52.8%) versus non-Hispanic whites (NHW; 36.6%) and Hispanics (H; 45.0%). Moreover, metformin alone was less effective in NHB versus NHW versus H youth. This study describes treatment-associated changes in adiponectin, insulin sensitivity, and β-cell function over time among the three racial/ethnic groups to understand potential mechanism(s) responsible for this racial/ethnic disparity. RESEARCH DESIGN AND METHODS TODAY participants underwent periodic oral glucose tolerance tests to determine insulin sensitivity, C-peptide index, and oral disposition index (oDI), with measurements of total and high-molecular-weight adiponectin (HMWA). RESULTS At baseline NHB had significantly lower HMWA than NHW and H and exhibited a significantly smaller increase (17.3% vs. 33.7% vs. 29.9%, respectively) during the first 6 months overall. increases in HMWA were associated with reductions in glycemic failure in the three racial/ethnic groups combined (hazard ratio 0.61, P CONCLUSIONS HMWA is a reliable biomarker of treatment response in youth with type 2 Diabetes. The diminutive treatment-associated increase in HMWA in NHB (∼50% lower) compared with NHW and H may explain the observed racial/ethnic disparity with higher therapeutic failure rates in NHB in TODAY.

  • Effects of Metformin, Metformin Plus Rosiglitazone, and Metformin Plus Lifestyle on insulin Sensitivity and [Beta]-Cell Function in TODAY: TODAY STUDY GROUP
    Diabetes Care, 2013
    Co-Authors: Silva A Arslanian, Fida Bacha, Sonia Caprio, Robin Goland, Morey W Haymond, Lynne L Levitsky, Laura Pyle, Marisa Payan, Neil H White
    Abstract:

    OBJECTIVE-The Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY) trial demonstrated that combination therapy with metformin plus rosiglitazone provided superior durability of glycemic control compared with metformin alone, with significantly lower treatment failure rates (38.6 vs. 51.7%), and metformin plus lifestyle was intermediate. Herein we describe the temporal changes in measures of s-cell function and insulin sensitivity over a 4-year period among the three treatments. RESEARCH DESIGN AND METHODS-TODAY participants (699) were tested periodically with an oral glucose tolerance test to determine insulin sensitivity (1/fasting insulin [1/I^sub F^]), insulinogenic index (?I^sub 30^/?G^sub 30^) or C-peptide index (?C^sub 30^/?G^sub 30^), and s-cell function relative to insulin sensitivity (oral disposition index [oDI]). RESULTS-During the first 6 months, metformin plus rosiglitazone exhibited a significantly greater improvement in insulin sensitivity and oDI versus metformin alone and versus metformin plus lifestyle; these improvements were sustained over 48 months of TODAY. Irrespective of treatment, those who failed to maintain glycemic control had significantly lower s-cell function (~50%), higher fasting glucose concentration, and higher HbA^sub 1c^ at randomization compared with those who did not fail. CONCLUSIONS-The beneficial change in insulin sensitivity and the resultant lower burden on s-cell function achieved in the first 6 months with metformin plus rosiglitazone appear to be responsible for its superior glycemic durability over metformin alone and metformin plus lifestyle. However, initial s-cell reserve and HbA^sub 1c^ at randomization are independent predictors of glycemic durability. Therefore, efforts to preserve s-cell function before significant loss occurs and to reduce HbA^sub 1c^ may be beneficial in the treatment of youth with type 2 Diabetes.