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Adiponectin, Insulin Sensitivity, ?-Cell Function, and Racial/Ethnic Disparity in Treatment Failure Rates in TODAY.

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 ?-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 < 0.0001) and in each race/ethnicity separately. Over time, HMWA was significantly lower in those who failed versus did not fail treatment, irrespective of race/ethnicity. There were no differences in treatment-associated temporal changes in insulin sensitivity, C-peptide index, and oDI among the three racial/ethnic groups. 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.

SUBMITTER: Arslanian S

PROVIDER: S-EPMC5180463 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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Adiponectin, Insulin Sensitivity, β-Cell Function, and Racial/Ethnic Disparity in Treatment Failure Rates in TODAY.

Arslanian Silva S El Ghormli Laure L Bacha Fida F Caprio Sonia S Goland Robin R Haymond Morey W MW Levitsky Lynne L Nadeau Kristen J KJ White Neil H NH Willi Steven M SM

Diabetes care 20161101 1

<h4>Objective</h4>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 adipo ...[more]

PMID: 27803118

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Project description:Lean Asian Indians are less insulin sensitive compared with Chinese and Malays, but the pancreatic beta-cell function among these ethnic groups has yet to be studied in depth. We aimed to study beta-cell function in relation to insulin sensitivity among individuals of Chinese, Malay and Asian-Indian ethnicity living in Singapore.This is a sub-group analysis of 59 normoglycemic lean (body mass index (BMI) <23?kg?m(-)(2)) adult males (14 Chinese, 21 Malays and 24 Asian Indians) from the Singapore Adults Metabolism Study. Insulin sensitivity was determined using fasting state indices (homeostatic model assessment-insulin resistance), the euglycemic-hyperinsulinemic clamp (ISI-clamp) and a liquid mixed-meal tolerance test (LMMTT) (Matsuda insulin sensitivity index (ISI-Mat)). Beta-cell function was assessed using fasting state indices (homeostatic model assessment-beta-cell function) and from the LMMTT (insulinogenic index and insulin secretion index). The oral disposition index (DI), a measure of beta-cell function relative to insulin sensitivity during the LMMTT, was calculated as a product of ISI-Mat and insulin secretion index.Asian Indians had higher waist circumference and percent body fat than Chinese and Malays despite similar BMI. Overall, Asian Indians were the least insulin sensitive whereas the Chinese were most insulin sensitive. Asian Indians had higher beta-cell function compared with Chinese or Malays but these were not statistically different. Malays had the highest incremental area under the curve for glucose during LMMTT compared with Asian Indians and Chinese. However, there were no significant ethnic differences in the incremental insulin area under the curve. The oral DI was the lowest in Malays, followed by Asian Indians and Chinese.Among lean Asians, Chinese are the most insulin sensitive whereas Asian Indians are the least insulin sensitive. However, Malays demonstrate higher postprandial glucose excursion with lower beta-cell response compare with Chinese or Asian Indians. The paths leading to type 2 diabetes mellitus might differ between these Asian ethnic groups.

Dataset Information

Adiponectin, Insulin Sensitivity, ?-Cell Function, and Racial/Ethnic Disparity in Treatment Failure Rates in TODAY.

Publications

Adiponectin, Insulin Sensitivity, β-Cell Function, and Racial/Ethnic Disparity in Treatment Failure Rates in TODAY.

Similar Datasets

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