hyperfiltration was a strong risk factor for developing elevated UACR. Other risk factors included glycated hemoglobin levels, or HbA1c, which indicates excessive sugar in the bloodstream.
That was expected, but they demonstrated other important risk factors as well: hypertension, serum uric acid and various parameters of beta cell function.
“ These risk factors are potentially modifiable,” says Dr. Bjornstad.“ That’ s important, because it means you can potentially target them with interventions.”
“ The level of detail in these data lets us tease out associations,” says Dr. Zeitler.“ If one of these kids has neuropathy, what meds are they on? What was their HbA1c over time? If you look at kids who develop neuropathy, what was the difference between them and kids who didn’ t? We can figure that out.”
The TODAY Study Group is in the process of figuring that out right now, starting with a suite of six papers, including the nephropathy paper led by Dr. Bjornstad( 3), appearing in Diabetes Care. Those papers will take a first look at an array of associations: the impact of cholesterol on retinopathy, the impact of pregnancy, as well as ethnic and racial associations and social determinants of health. Dr. Bjornstad’ s paper, for example, found that female participants and participants of Hispanic heritage had a heightened risk of hyperfiltration.
The question now is why.
WIDENING AND DEEPENING THE DATA
“ This disorder, in the U. S. anyway, disproportionately affects minorities and other socially disadvantaged populations,” says Dr. Zeitler.“ But the reasons are very complex. When you say Hispanic people are more likely to get kidney disease, is that because of ancestry? Poverty? Lack of access to treatment? Hypertension?”
The factors at play
One of the most pressing problems with youth-onset type 2 diabetes is the lack of treatment options that work. One intervention that has a pronounced effect, however, is bariatric surgery.
In fact, when Dr. Bjornstad compared rates of diabetic kidney disease of participants in TODAY to participants in Teen-LABS, the largest-ever study of bariatric surgery in adolescents( 5), the results were dramatic( 6). Five years out from surgery, participants in Teen-LABS had 16-fold lower odds for hyperfiltration and 27-fold lower odds for elevated UAE than TODAY participants.
“ Clearly bariatric surgery protects the kidney, but weight loss surgery is not for everyone,” Dr. Bjornstad says.“ We need to understand now how surgery protects. Attaining a normal BMI is part of it, but there are other factors at play.”
Dr. Bjornstad’ s ongoing study, IMPROVE-T2D, seeks to understand those factors. So far, they’ ve enrolled 16 of 30 participants, all of whom have type 2 diabetes and qualify to undergo bariatric surgery per clinical indications. IMPROVE-T2D integrates state-of-the-art physiology testing with MRI and kidney biopsies to understand how bariatric surgery mitigates diabetic kidney disease on a molecular level.
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