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February 19, 2014

Diagnosis and Symptoms, LADA and MODY

Question from Springfield, Massachusetts, USA:

My 13-year-old daughter was diagnosed with type 1 in August 2013. Because she has no antibodies, a normal C-Peptide level and other clinical presentations, a strong family history of type 1 diabetes, and being African American, she was tested for MODY but also put on 27 units of nighttime Lantus and Humalog with a ratio of 1 unit per 7 grams of carbohydrates. We did this regimen until December when her MODY test came back indicating a genetic defect in the PDX1 gene, consistent with MODY4. Because this form is so rare, no one believed this could be possible, however the endocrinologist said to try glyburide, to stop insulin. So far, two months later, things are still going well and our daughter is achieving good control with glyburide. My daughter is thrilled and has smiled for the first time since her type 1 diagnosis six months ago. I have been excited but am afraid that this is a mistake that will soon end. Could this really still be type 1 and oral medications are only working because it’s the honeymoon period?


Our ability to make a genetic diagnosis of various types of diabetes is still not as specific as we would like it to be but the good response that you report on sulfonylurea diabetes medications and coming off insulin is hopeful. Time will really tell whether or not she will need insulin resumed, but a lot will also depend upon what she does with her weight, exercise and food choices since these also mandate how much insulin response she requires. As long as you are monitoring blood glucose levels and working with your diabetes team, this should be a good indicator of what your daughter will require and when, if ever, there is a change in therapy needed.

Additional comments from Dr. David Schwartz:
While NO lab test is 100% accurate all the time, DNA testing, if done by a good laboratory, is pretty darn accurate.

Not all patients with type 1 diabetes mellitus have antibodies and, depending on what part of the medical literature you might put your money on, it could be 60 to 90% of type 1 patients have antibodies. Might you know which antibodies were done? The common ones are “GAD” antibodies, “IA2” (aka “Tyrosine Kinase” aka “ICA-512”) antibodies, “insulin” antibodies, and “Zinc Transporter 8” (aka “ZnT8”) antibodies. The GAD and ZnT8 may be the most sensitive. Having all four antibodies negative really puts a low light on classic autoimmune type 1 diabetes mellitus.

Since MODY 4 is so rare, I’d guess that diagnosis is true. Do you know which laboratory did the test? It was most probably Athena Diagnostics. You might contact Dr. Siri Greeley at the University of Chicago; his research laboratory might be able to confirm the prior result.