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From Watchung, New Jersey, USA:

Our thirteen year old son was diagnosed with Type 1 diabetes 2 months ago. He is physically mature at age thirteen, having started puberty at age 9. He is 5'8" and 150 pounds. He displayed no symptoms on diagnosis, but sugar was detected in his urine at a routine physical (500's range). Verification with a pediatric endocrinologist confirmed an HbA1c of 8.5, with a normal C-peptide range. Currently, he is taking two shots per day (14N, 5N, pork, with a sliding scale of R).

Based on the following testing done after the initial diagnosis, I question whether he has Type 1 diabetes, or MODY, or some other malady. The basis for my question is as follows:

  1. Antibody testing done 3 weeks after diagnosis indicated that he had neither antibodies to islet cells (usually found in 70-80% of Type 1 cases) nor antibodies to GAD (usually found in 80-95% of cases). If we combine these two variables, the likelihood of a Type 1 diagnosis seems minuscule. Children with Diabetes has said with respect to antibody tests that "it will be positive in the case of Type 1 Diabetes and negative for Type 2."

  2. After an overnight fasting mixed meal test (several hour duration) his final blood glucose reading was 177.

  3. Six weeks after diagnosis, his HbA1c was 6.2

  4. You have previously said that MODY 1, 2 and 3 can all appear under the age of 20, although the likelihood is about 1%. "A significant portion of these children remain undiagnosed as having MODY" and are simply diagnosed as Type 1.

  5. According to Children with Diabetes, MODY can be treated "with one or the other of two new oral drugs, metformin, which reduces the liver output of glucose and troglitazone, which makes the insulin receptor more receptive."

Based on the above information,

  1. Is it possible our son has MODY 1, 2 or 3? Obviously, oral treatment, exercise and diet control is preferable to a similar regimen, but with shots instead of oral medication.

  2. Could we put our son on oral medication to see how he will do (understanding that the results may be clouded if he is still in his honeymoon period - however, is there a honey moon period if he has MODY or is it only referred to in Type 1 diabetes)?

  3. Should we do genetic testing to confirm whether there are any chromosomal abnormalities tagged to MODY?

  4. If he does in fact have MODY, is the pork insulin he is on in any way detrimental to his functioning islet cells (versus use of human insulin)?

  5. Past MODY, are there any other disorders that could be presenting themselves, given the knowledge of his condition we now have.

We anxiously await your hopefully positive response to our question.


The occasional problem of making a specific diagnosis in children who seem to have typical Type 1 Diabetes clinically but are antibody negative has attracted a good deal of attention in recent years. The importance of achieving and maintaining good control is much the same whatever the precise diagnosis; but since this can sometimes be achieved without the need for insulin in this group, families often like to know even though it can be a tedious and expensive business.

I am sure that your son is in fact a Type 1 Diabetic and I will try to explain why. To begin with though you should talk to your diabetes care team to get further details of the antibody profile. In the U.S. and Canada, it is usual to do three antibodies initially ICA512 and anti-GAD which has already been done; but also anti-insulin antibodies. It would be useful to know if your son is also negative for the last one too. Also tests are often done for linked autoimmune conditions by looking for anti-endomyseal antibodies (celiac syndrome) and anti-21-hydoxylase antibodies (adrenal insufficiency). If either of these were positive it would suggest that the diabetes too is auto-immune.

Only a small proportion of Caucasian children are antibody negative and at the moment it is supposed that this is a matter of not yet looking for the right antibodies. However more than half of African American and Hispanic new onset cases do not have antibodies and the reason for this is not yet clear. Outside of these groups there are, as you pointed out three types of MODY (Maturity Onset Diabetes in the Young). The commonest of these is MODY2 and is due to a genetic defect in the enzyme Glucokinase, there is usually a strong family history and they are seldom insulin dependant. MODY 1 and MODY3 have the same strong family history and are more likely to need insulin, the defects here are in a protein called HNF (Hepatic Nuclear Factor). All there types can be seen in childhood. Then there are some very rare possibilities like defects in various parts of the insulin receptor on the cell surface which make for insulin resistance rather than insulin deficiency. Unlike your son at the moment they eventually require large doses of insulin. Another group are the 'mitochondrial' diabetes syndromes. These are inherited from the maternal line, are usually mild; but are often associated with other abnormalities, like deafness, muscle weakness etc. Your son does not seem to be overweight for his height and that is another strike against one of the MODY variants.

To answer some of your other queries, the resolution of the A1c is to be expected as someone moves into the honeymoon period; it is not indicative of MODY or any of the other antibody negative forms of diabetes. A fasting glucose level of 177 mg/dl is abnormal; but it was not clear to me what the relation to the test meal was. I think that it would be a mistake to discontinue insulin at this stage; but if you later found that your son's blood sugars could be permanently controlled on less than 0.25 Units/kg body wt/day of total insulin it would be reasonable to try to talk his doctor into seeing if either metformin or troglitazone would make him insulin independent. If you tried that it would be important at the same time to try to get a specific diagnosis.


Original posting 30 Aug 97


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