Obesity and youth diabetes: distinguishing characteristics between islet cell antibody positive vs. negative patients over time

Abstract

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.

The changing face of diabetes in youth: lessons learned from studies of type 2 diabetes

“…In addition, Ab + T2D patients were mostly non‐Hispanic whites, with less female representation and less frequent family history of DM. An evaluation of our clinic population of obese Ab + versus Ab – T2D patients at diagnosis and their clinical course over time revealed similar findings: Ab + youth were younger, had higher rates of ketosis, higher HbA1c and glucose concentrations, and lower insulin and C‐peptide concentration, compared with Ab – patients . The latter patients had higher BMI Z‐scores and cardiometabolic risk factors at diagnosis, and such differences persisted over time.…”

“…Of the 1206 youth screened and clinically considered to have T2D, 118 (9.8%) were antibody positive: 5.9% were positive for a single antibody and 3.9% were positive for both antibodies, making them ineligible for the TODAY study. In smaller scale studies, the reported rates of positive pancreatic autoantibodies in youth clinically diagnosed with T2D vary from 10% to 75% …”

“…In making a clinical diagnosis of T2D, the major diagnostic criterion is overweight/obesity. However, with the increasing rates of obesity in children with autoimmune T1D, the clinical distinction between youth with T2D and obese youth with autoimmune T1D is difficult and imperfect without measuring pancreatic autoantibodies . Between two periods, 1979–1989 and 1990–1998, the prevalence of overweight at diagnosis of T1D in children tripled .…”

“…The distinction between youth with T2D and obese youth with autoimmune T1D is further blurred because, not infrequently, youth with T2D present with diabetic ketoacidosis . Moreover, and as stated under the above, a number of youth clinically diagnosed with T2D have evidence of islet autoimmunity, with autoantibodies present in 10–75% of patients . Several hypotheses and terminologies have been proposed, such as hybrid diabetes, double diabetes, diabetes type 1.5, and latent autoimmune diabetes of youth, to refer to this subset of young patients with a clinical phenotype consistent with T2D and evidence of autoimmunity consistent with T1D …”

“…The latter patients had higher BMI Z‐scores and cardiometabolic risk factors at diagnosis, and such differences persisted over time. Longitudinal data analysis uncovered that deterioration in BMI Z‐score significantly affected systolic blood pressure and ALT, but lipid profile was mostly affected by HbA1c and glycemic control regardless of antibody status …”