Browsing by Author "Younes, Naji"

Now showing 1 - 3 of 3
  • Thumbnail Image
    Item
    Association of Glycemia with Insulin Sensitivity and β-cell Function in Adults with Early Type 2 Diabetes on Metformin Alone
    (Elsevier, 2021) Utzschneider, Kristina M.; Younes, Naji; Rasouli, Neda; Barzilay, Joshua; Banerji, Mary Ann; Cohen, Robert M.; Gonzalez, Erica V.; Mather, Kieren J.; Ismail-Beigi, Faramarz; Raskin, Philip; Wexler, Deborah J.; Lachin, John M.; Kahn, Steven E.; GRADE Research Group; Medicine, School of Medicine
    Aims: Evaluate the relationship between measures of glycemia with β-cell function and insulin sensitivity in adults with early type 2 diabetes mellitus (T2DM). Methods: This cross-sectional analysis evaluated baseline data from 3108 adults with T2DM <10 years treated with metformin alone enrolled in the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness (GRADE) Study. Insulin and C-peptide responses and insulin sensitivity were calculated from 2-hour oral glucose tolerance tests. Regression models evaluated the relationships between glycemic measures (HbA1c, fasting and 2-hour glucose), measures of β-cell function and insulin sensitivity. Results: Insulin and C-peptide responses were inversely associated with insulin sensitivity. Glycemic measures were inversely associated with insulin and C-peptide responses adjusted for insulin sensitivity. HbA1c demonstrated modest associations with β-cell function (range: r −0.22 to −0.35). Fasting and 2-hour glucose were associated with early insulin and C-peptide responses (range: r −0.37 to −0.40) as well as late insulin and total insulin and C-peptide responses (range: r −0.50 to −0.60). Conclusion: Glycemia is strongly associated with β-cell dysfunction in adults with early T2DM treated with metformin alone. Efforts to improve glycemia should focus on interventions aimed at improving β-cell function.
  • Thumbnail Image
    Item
    Islet Autoimmunity is Highly Prevalent and Associated With Diminished β-Cell Function in Patients With Type 2 Diabetes in the Grade Study
    (American Diabetes Association, 2022-01-21) Brooks-Worrell, Barbara; Hampe, Christiane S.; Hattery, Erica G.; Palomino, Brenda; Zangeneh, Sahar Z.; Utzschneider, Kristina; Kahn, Steven E.; Larkin, Mary E.; Johnson, Mary L.; Mather, Kieren J.; Younes, Naji; Rasouli, Neda; Desouza, Cyrus; Cohen, Robert M.; Park, Jean Y.; Florez, Hermes J.; Valencia, Willy Marcos; GRADE β-cell Ancillary Study Network; Shojaie, Ali; Palmer, Jerry P.; Balasubramanyam, Ashok; Medicine, School of Medicine
    Islet autoimmunity may contribute to β-cell dysfunction in type 2 diabetes (T2D). Its prevalence and clinical significance have not been rigorously determined. In this ancillary study to the Glycemia Reduction Approaches in Diabetes-A Comparative Effectiveness (GRADE) Study, we investigated the prevalence of cellular and humoral islet autoimmunity in patients with T2D duration 4·0±3·0 y, HbA1c 7·5±0·5% on metformin alone. We measured T cell autoreactivity against islet proteins, islet autoantibodies against GAD65, IA2, ZnT8, and β-cell function. Cellular islet autoimmunity was present in 41·3%, humoral islet autoimmunity in 13·5%, and both in 5·3%. β-cell function calculated as iAUC-CG and ΔC-peptide(0- 30)/Δglucose(0-30) from an oral glucose tolerance test was lower among T cell-positives (T+) than T cell-negatives (T-) using two different adjustments for insulin sensitivity (iAUC-CG: 13·2% [95% CI 0·3, 24·4%] or 11·4% [95% CI 0·4, 21·2%] lower; ΔC-peptide(0-30)/Δglucose(0-30)) 19% [95% CI 3·1, 32·3%] or 17·7% [95% CI 2·6, 30·5%] lower). T+ patients had 17% higher HbA1c (95% CI 0·07, 0·28) and 7·7 mg/dL higher fasting plasma glucose levels (95% CI 0·2,15·3) than T- patients. We conclude that islet autoimmunity is much more prevalent in T2D patients than previously reported. T cell-mediated autoimmunity is associated with diminished β-cell function and worse glycemic control.
  • Thumbnail Image
    Item
    Shape of the OGTT glucose response curve: relationship with β-cell function and differences by sex, race, and BMI in adults with early type 2 diabetes treated with metformin
    (BMJ, 2021) Utzschneider, Kristina M.; Younes, Naji; Rasouli, Neda; Barzilay, Joshua I.; Banerji, Mary Ann; Cohen, Robert M.; Gonzalez, Erica V.; Ismail-Beigi, Faramarz; Mather, Kieren J.; Raskin, Philip; Wexler, Deborah J.; Lachin, John M.; Kahn, Steven E.; GRADE Research Group; Medicine, School of Medicine
    Introduction: The shape of the glucose curve during an oral glucose tolerance test (OGTT) reflects β-cell function in populations without diabetes but has not been as well studied in those with diabetes. A monophasic shape has been associated with higher risk of diabetes, while a biphasic pattern has been associated with lower risk. We sought to determine if phenotypic or metabolic characteristics were associated with glucose response curve shape in adults with type 2 diabetes treated with metformin alone. Research design and methods: This is a cross-sectional analysis of 3108 metformin-treated adults with type 2 diabetes diagnosed <10 years who underwent 2-hour 75 g OGTT at baseline as part of the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE). Insulin sensitivity (homeostasis model of insulin sensitivity, HOMA2-S) and β-cell function (early, late, and total incremental insulin and C peptide responses adjusted for HOMA2-S) were calculated. Glucose curve shape was classified as monophasic, biphasic, or continuous rise. Results: The monophasic profile was the most common (67.8% monophasic, 5.5% biphasic, 26.7% continuous rise). The monophasic subgroup was younger, more likely male and white, and had higher body mass index (BMI), while the continuous rise subgroup was more likely female and African American/black. HOMA2-S and fasting glucose did not differ among the subgroups. The biphasic subgroup had the highest early, late, and total insulin and C peptide responses (all p<0.05 vs monophasic and continuous rise). Compared with the monophasic subgroup, the continuous rise subgroup had similar early insulin (p=0.3) and C peptide (p=0.6) responses but lower late insulin (p<0.001) and total insulin (p=0.008) and C peptide (p<0.001) responses. Conclusions: Based on the large multiethnic GRADE cohort, sex, race, age, and BMI were found to be important determinants of the shape of the glucose response curve. A pattern of a continuously rising glucose at 2 hours reflected reduced β-cell function and may portend increased glycemic failure rates.