1.
Serum apolipoproteins and apolipoprotein-defined lipoprotein subclasses: a hypothesis-generating prospective study of cardiovascular events in T1D.
Basu, A, Bebu, I, Jenkins, AJ, Stoner, JA, Zhang, Y, Klein, RL, Lopes-Virella, MF, Garvey, WT, Budoff, MJ, Alaupovic, P, et al
Journal of lipid research. 2019;(8):1432-1439
Abstract
APOB, APOC3, and APOE and apolipoprotein-defined lipoprotein subclasses (ADLSs; based on qualitative apolipoprotein complement) have been associated with dyslipidemia and CVD. Our main objective was to define associations of serum apolipoproteins and ADLSs with "any CVD" and "major atherosclerotic cardiovascular events" (MACEs) in a prospective study of T1D. Serum apolipoproteins and ADLSs (14 biomarkers in total) were measured in sera (obtained between 1997 and 2000) from a subset (n = 465) of the Epidemiology of Diabetes Interventions and Complications cohort. Prospective associations of "any CVD" (myocardial infarction, stroke, confirmed angina, silent myocardial infarction, revascularization, or congestive heart failure) and MACEs (fatal or nonfatal myocardial infarction or stroke), over 5,943 and 6,180 patient-years follow-up, respectively, were investigated using Cox proportional hazards models that were unadjusted and adjusted for risk factors. During 15 years of follow-up, 50 "any CVD" events and 24 MACEs occurred. Nominally significant positive univariate associations with "any CVD" were APOB, APOC3 and its subfractions [heparin precipitate, heparin-soluble (HS)], and ADLS-defined Lp-B. In adjusted analyses, APOC3-HS remained nominally significant. Nominally significant positive univariate associations with MACEs were APOC3 and its subfractions and Lp-B:C; those with total APOC3 and APOC3-HS persisted in adjusted analyses. However, these associations did not reach significance after adjusting for multiple testing. There were no significant associations of APOA1, APOA2, APOE, or other ADLSs with either "any CVD" or MACEs. These hypothesis-generating data suggest that total serum APOC3 and APOC3 in HDL are potentially important predictive biomarkers for any CVD and MACEs in adults with T1D.
2.
Metabolomic biomarkers in diabetic kidney diseases--A systematic review.
Zhang, Y, Zhang, S, Wang, G
Journal of diabetes and its complications. 2015;(8):1345-51
Abstract
Diabetic kidney disease (DKD) is generally characterized by increasing albuminuria in diabetic patients; however, few biomarkers are available to facilitate early diagnosis of this disease. The application of metabolomics has shown promises addressing this need. In this review, we conducted a search about metabolomic biomarkers in DKD patients through MEDLINE, EMBASE, and Cochrane Database up to the end of March, 2015. 12 eligible studies were selected and evaluated subsequently through the use of QUADOMICS, a quality assessment tool. 7 of the 12 included studies were classified as 'high quality'. We also recorded specific study characteristics including participants' characteristics, metabolomic techniques, sample types, and significantly altered metabolites between DKD and control groups. Products of lipid metabolisms including esterified and non-esterified fatty acids, carnitines, phospholipids and metabolites involved in branch-chained amino acids and aromatic amino acids metabolisms were frequently affected biomarkers of DKD. Other differential metabolites were also found, while some of their associations with DKD were unclear. Further more studies are required to test these findings in larger, diverse ethnic populations with elaborate study designs, and finally we could translate them into the benefits of DKD patients.
3.
Diabetic ketoacidosis at diagnosis influences complete remission after treatment with hematopoietic stem cell transplantation in adolescents with type 1 diabetes.
Gu, W, Hu, J, Wang, W, Li, L, Tang, W, Sun, S, Cui, W, Ye, L, Zhang, Y, Hong, J, et al
Diabetes care. 2012;(7):1413-9
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Abstract
OBJECTIVE To determine if autologous nonmyeloablative hematopoietic stem cell transplantation (AHSCT) was beneficial for type 1 diabetic adolescents with diabetic ketoacidosis (DKA) at diagnosis. RESEARCH DESIGN AND METHODS We enrolled 28 patients with type 1 diabetes, aged 14-30 years, in a prospective AHSCT phase II clinical trial. HSCs were harvested from the peripheral blood after pretreatment consisting of a combination of cyclophosphamide and antithymocyte globulin. Changes in the exogenous insulin requirement were observed and serum levels of HbA(1c), C-peptide, and anti-glutamic acid decarboxylase antibody were measured before and after the AHSCT. RESULTS After transplantation, complete remission (CR), defined as insulin independence, was observed in 15 of 28 patients (53.6%) over a mean period of 19.3 months during a follow-up ranging from 4 to 42 months. The non-DKA patients achieved a greater CR rate than the DKA patients (70.6% in non-DKA vs. 27.3% in DKA, P = 0.051). In the non-DKA group, the levels of fasting C-peptide, peak value during oral glucose tolerance test (C(max)), and area under C-peptide release curve during oral glucose tolerance test were enhanced significantly 1 month after transplantation and remained high during the 24-month follow-up (all P < 0.05). In the DKA group, significant elevation of fasting C-peptide levels and C(max) levels was observed only at 18 and 6 months, respectively. There was no mortality. CONCLUSIONS We have performed AHSCT in 28 patients with type 1 diabetes. The data show AHSCT to be an effective long-term treatment for insulin dependence that achieved a greater efficacy in patients without DKA at diagnosis.