QUESTION--I have a 18y/o male referred to me for management of diabetes diagnosed one year ago. His HgA1c was 9.8 increasing from 6.5 over the past year, and he was started on metformin. He has strong family history(father and father's side grandparents, mother's side grandparents) for diabetes (Mainly Type 2 according to history.) His metformin seems to be controlling his glucoses for the time being. However I was suspicious for Type 1 Diabetes (he has  no acanthosis,  BMI 22.9, weighs 76kg but mild central fat, sedentary lifestyle), so I checked for GAD, C peptide and Insulin level approximately 3-4 hours after a meal with following results:  glucose: 14.4 mmol/L, C peptide: 1940 (298-2350 pmol/L), insulin 313 (40-190 pmol/L). His GAD antibodies were >250 IU/ml (<5.0).
Even though he is still producing insulin, the literature seems to be in favor of starting insulin in this case to theoretically preserve Beta cell function and intense glycemic control in Type 1 Diabetes. However I am concerned for hypoglycemia even if starting on low dose insulin (thinking of starting Lantus 3units and Humalog 2units premeal and stopping metformin).  Furthermore, given his good glucose response to metformin and still producing insulin, should I just monitor on metformin for now (checking periodically for C peptide and glucose control) given he has some Type 2 features,  and r/o MODY given his strong family history. Any help would be appreciated. Thank you.Dr. S

RESPONSE--This patient has features of both type 1 (young, elevated GAD antibody, normal BMI--though needs to be race/ethnicity adjusted), and type 2 (family history, indolent onset, possible feature of insulin resistance).  He has exhibited deterioration in glycemic control as evidenced by the high A1c and very high fasting glucose.  In this situation, he should be treated as though he has type 1 diabetes, even though he still has a "normal" c-peptide, as it is likely that he will develop progressive insulin deficiency.  There may also be a beta cell protective effect with early insulin therapy, and the persistence of detectable c-peptide, even if it is below the normal range, portends a favorable prognosis in terms of ease glucose control, fewer hypoglycemic events, and lower risk of microvascular complications.
Given his current fasting glucose, which is quite high, it is appropriate to start weight based insulin of approximately 0.5 unit/kg, 50% basal, 50% bolus divided over 3 meals along with education for a consistent carbohydrate diet, glucose monitoring and targets, and hypoglycemia prevention and treatment.  If you are uncomfortable starting the full dose then it is important to provide a titration algorithm for the basal insulin self-adjustment such as:  "start at 10 units daily and increase by 2 unit every 3 days (up to a maximum of X unit) until the fasting glucose is below 130 mg/dl, provided that you have no overnight hypoglycemia."  Follow-up and adjustment of doses is essential.  Kathleen Dungan, MD, MPH