Objectives Metformin is the only oral therapy for youth with type 2 diabetes, but up to 50% require additional agents within 2 years of diagnosis. Extended‐release (XR) metformin formulations may improve adherence and tolerability–important mediators of treatment response–but data in youth is lacking. To evaluate rates of gastrointestinal (GI) symptoms in patients treated with metformin (SR and XR) and the change in GI symptoms after changes in metformin therapy. Research Design and Methods Retrospective chart review of youth with Type 2 or prediabetes seen in a multidisciplinary clinic during 2016–2019. Results Of 488 eligible patients, 41.4% and 21.1% were taking metformin SR and XR respectively, with most (58%, n = 178/305) taking a total daily dose of ≥1500 mg/day. Those not on metformin tended to be younger, leaner, and had lower HbA1cs than those taking metformin, p < 0.05. Thirty percentage of patients described GI symptoms, most commonly, abdominal pain and diarrhea. There was no difference in GI symptoms in those on SR versus XR (18.3% vs. 14.6%, p = 0.41). Among patients who initiated metformin, rates of GI symptoms increased (13%–33%, p = 0.001, n = 99), while rates tended to decrease when metformin was discontinued (28%–12%, p = 0.076, n = 50). Rates of GI symptoms were unchanged among those that switched from SR to XR metformin (17% vs. 14%, p = 0.6, n = 58). Conclusions GI symptoms are common in youth with type 2 diabetes taking metformin XR and SR. Adjuncts to mitigate GI symptoms in youth on metformin therapy are needed to improve quality of life and medication adherence.
Youth with obesity have an increased risk for cardiometabolic disease, but identifying those at highest risk remains a challenge. Four biomarkers that might serve this purpose are “by products” of clinical NMR LipoProfile® lipid testing: LPIR (Lipoprotein Insulin Resistance Index), GlycA (inflammation marker), BCAA (total branched-chain amino acids), and glycine. All are strongly related to insulin resistance and type 2 diabetes (T2DM) in adults (glycine inversely) and are independent of biological and methodological variations in insulin assays. However, their clinical utility in youth is unclear. We compared fasting levels of these biomarkers in 186 youth (42 lean normal glucose tolerant (NGT), 88 obese NGT, 23 with prediabetes (PreDM), and 33 with T2DM. All four biomarkers were associated with obesity and glycemia in youth. LPIR and GlycA were highest in youth with PreDM and T2DM, whereas glycine was lowest in youth with T2DM. While all four were correlated with HOMA-IR (Homeostatic Model Assessment for Insulin Resistance), LPIR had the strongest correlation (LPIR: r = 0.6; GlycA: r = 0.4, glycine: r = −0.4, BCAA: r = 0.2, all P < 0.01). All four markers correlated with HbA1c (LPIR, GlycA, BCAA: r ≥ 0.3 and glycine: r = −0.3, all P < 0.001). In multi-variable regression models, LPIR, GlycA, and glycine were independently associated with HOMA-IR (Adjusted R2 = 0.473, P < 0.001) and LPIR, glycine, and BCAA were independently associated with HbA1c (Adjusted R2 = 0.33, P < 0.001). An LPIR index of >44 was associated with elevated blood pressure, BMI, and dyslipidemia. Plasma NMR-derived markers were related to adverse markers of cardiometabolic risk in youth. LPIR, either alone or in combination with GlycA, should be explored as a non-insulin dependent predictive tool for development of insulin resistance and diabetes in youth.Clinical Trial RegistrationClinicaltrials.gov, identifier NCT:02960659
Youth with obesity have increased risk for cardiometabolic (CM) disease but identifying those at highest risk remains a challenge. 4 potential biomarkers are “byproducts” of clinical NMR LipoProfile® lipid testing: LPIR (Lipoprotein Insulin Resistance Index), GlycA (inflammation marker), BCAA (total branched-chain amino acids), and glycine. All are strongly related to insulin resistance (IR) and type 2 diabetes (T2D) in adults (glycine inversely), but their clinical utility in youth is unclear. We compared fasting levels of these biomarkers in 184 youth (42 lean normal glucose tolerant (NGT), 88 obese NGT and 54 obese with abnormal glucose tolerance (AGT; 20 with T2D and 34 with prediabetes) and determined their relationships with HOMA-IR (homeostatic model of IR) and hemoglobin A1c (HbA1c). Compared to lean and obese NGT, AGT youth had higher systolic blood pressure and HbA1c (Table). All 4 biomarkers were higher in youth with obesity vs. lean, while only LPIR was higher in AGT youth vs. obese NGT (Table). While all 4 were correlated with HOMA-IR, LPIR had the strongest correlation (LPIR: r=0.6; GlycA: r=0.4, glycine: r=-0.4, BCAA: r=0.2, all P<0.01). All 4 correlated with HbA1c (GlycA, LPIR, BCAA: r≥0.3 and glycine: r=-0.3, all P<0.001). Plasma NMR-derived markers were related to CM risk in youth, with LPIR distinguishing between obese NGT and AGT. These biomarkers should be explored as predictive tools for development of IR and T2DM. Disclosure S.T. Chung: None. S. Matta: None. A. Meyers: None. C.K. Cravalho: None. A. Villalobos-Perez: None. L. Mabundo: None. A.B. Courville: None. M.L. Sampson: None. J.D. Otvos: Employee; Self; LabCorp. S.N. Magge: None. Funding National Institutes of Health (to S.T.C., L.M., A.B.C.)
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