This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Objective
Obese youth clinically diagnosed with type 2 diabetes (T2DM) frequently have evidence of islet cell autoimmunity. We investigated the clinical and biochemical differences, and therapeutic modalities amongst autoantibody positive (Ab+) vs. autoantibody negative (Ab-) youth at the time of diagnosis and over time in a multi-provider clinical setting.
Study Design
Chart review of 145 obese youth diagnosed with T2DM from January 2003 through July 2012. Of these, 70 patients were Ab+ and 75 Ab-. The two groups were compared with respect to clinical presentation, physical characteristics, laboratory data and therapeutic modalities at diagnosis and during follow up to assess the changes in these parameters associated with disease progression.
Results
At presentation, Ab+ youth with a clinical diagnosis of T2DM were younger, had higher rates of ketosis, higher HbA1c and glucose levels, and lower insulin and c-peptide concentrations compared with the Ab- group. The Ab- group had a higher BMI z-score and cardio-metabolic risk factors at diagnosis and such difference remained over time. Univariate analysis revealed that treatment modality had no effect on BMI in either group. Generalized estimating equations for longitudinal data analysis revealed that a) BMI z-score and DBP were significantly affected by duration of diabetes, b) SBP and ALT were affected by changes in BMI z-score, c) changes in HbA1c had an effect on lipid profile and cardio-metabolic risk factors regardless of antibody status.
Conclusions
Irrespective of antibody status and treatment modality, youth who present with obesity and diabetes, show no improvement in obesity status over time, with the deterioration in BMI z-score affecting BP and ALT, but the lipid profile being mostly impacted by HbA1c and glycemic control. Effective control of BMI and glycemia are needed to lessen the future macrovascular complications irrespective of antibody status.
Circulating concentrations of 13,14-dihydro-15-keto PGF2 alpha (DHKF2 alpha), luteinizing hormone (LH) and prolactin (PRL) have been measured in cyclic ewes treated with continuous infusions of oxytocin, in order to investigate the mechanism by which the treatment delays luteal regression. Continuous infusion of oxytocin reduced prostaglandin F2 alpha (PGF2 alpha) secretion but had no detectable direct effect on LH or PRL. Oxytocin (3 nmol h-1 i.v.) given from Day 12 or 13 until Day 18 after oestrus delayed luteolysis, eight out of nine treated ewes not returning to behavioural oestrus until Day 29.1 +/- 3.2 (mean +/- s.e.m.; cycle length of control ewes 16.7 +/- 0.3 days). In the ewe in which oxytocin failed to prevent luteolysis, luteal regression had commenced before oxytocin treatment was started. In three ewes undergoing delayed luteolysis (cycle lengths, 21, 24 and 25 days) basal concentrations of PGF2 alpha (measured as DHKF2 alpha) were unchanged, but there was only one episode of PGF2 alpha secretion compared with 20 episodes in three control ewes. Prolactin secretion was pulsatile during oxytocin infusion, and levels were low following infusion in ewes with cycle length greater than 25 days while the corpora lutea were maintained. Circulating PRL concentrations were high in ewes undergoing delayed luteolysis but there was not discrete episode of PRL secretion associated with the pre-ovulatory LH surge in these animals. To investigate the possibility that the pattern of PGF2 alpha secretion was affected by depletion of oxytocin from corpora lutea, ewes previously treated with oxytocin to delay luteolysis were given a luteolytic dose of cloprostenol on Day 21 after oestrus. The amount of oxytocin secreted in response to cloprostenol was less than 10% of that seen in ewes similarly treated on Days 11-13 after oestrus. Low levels of luteal oxytocin may therefore reduce PGF2 alpha secretion in ewes undergoing delayed luteolysis.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.