This is a clinical scenario drawn from my own practice. I’ll tell you what I plan to do, but I’m most interested in crowdsourcing a response from all of you to collectively determine best practice. So please answer the polling question and contribute your thoughts in the comments, whether you agree or disagree with my approach.
The Patient
A 31-year-old man presents for follow-up regarding suspected type 2 diabetes. He had no symptoms at his wellness appointment 6 weeks ago, but his A1c level was elevated, at 6.8%. His fasting blood glucose at the time was 148 mg/dL and the rest of his laboratory work, including a comprehensive metabolic panel and lipid panel, was normal. All his laboratory work, including his A1c result, was normal 3 years ago. Of note, the patient reports that he has an uncle and an aunt with diabetes.
After receiving the call about his elevated A1c, the patient changed his diet and started jogging again after 5 years of sedentary behavior. Still, he is interested in medication to treat his obesity (body mass index, 31; waist circumference, 130 cm) and suspected case of diabetes. He agrees to start semaglutide at 0.25 mg once a week for the first 4 weeks.
During a telehealth appointment 1 month after treatment initiation, the patient is excited to report that his lifestyle regimen plus semaglutide have resulted in a weight loss of 5 kg. He does feel more tired, but he attributes this fatigue to his new exercise regimen. At this visit, his semaglutide dose is increased to 0.5 mg.
The patient undergoes another round of blood work 2 months later. Now the labs indicate that his A1c has actually risen, to 7.7%. The patient is frustrated because he has continued to lose weight and has adhered to his regimen of behavioral changes and pharmacotherapy. His fasting blood glucose at home is consistently higher than 150 mg/dL.
Dr Vega’s Take
The answer, dear reader, is choice 2: check for islet cell autoantibodies. I have hundreds of patients with diabetes in my practice, and although every patient is quite unique, there are clearly defined patterns to the disease course of type 2 diabetes. The vast majority of patients with type 2 diabetes have overweight or obesity and often have additional metabolic abnormalities, such as hypertriglyceridemia or metabolic dysfunction–associated steatotic liver disease, at the time of diagnosis.
However, there are times when a patient’s type 2 diabetes disease pattern does not align with what we commonly recognize or expect. This patient’s case is a prime example: He is taking a highly effective medication (semaglutide) and following behavioral recommendations, yet his A1c level is worsening.
One key tenet I have learned again and again in clinical practice is to take the time (I know, no one has enough of it!) to step back and reevaluate my presumptions when a case veers off the typical path. For this patient, once I considered the fairly rapid degradation in glycemic control with weight loss in the setting of an effective treatment for type 2 diabetes, the possible etiology became clear: type 1 diabetes.
There are many reasons why type 1 diabetes might not have been initially considered in this case. First and foremost, 90%-95% of all diabetes cases in the United States are type 2. Plus, the prevalence of type 2 diabetes keeps rising — especially among adolescents and young adults. As clinicians, we are more inclined to diagnose type 2 vs type 1 diabetes, given that we see so many more cases of type 2 diabetes.
But isn’t this 31-year-old patient too old to develop type 1 diabetes? Actually, although the incidence rate of type 1 diabetes in the United States is highest among 10- to 14-year-old children, incident cases among US adults are higher relative to children and adolescents. It’s simple math: There are many more adults than children, and type 1 diabetes can be diagnosed at any age.
Risk factors for type 1 diabetes include a family history of type 1 diabetes and a personal or family history of autoimmune conditions such as thyroiditis, celiac disease, or vitiligo. Remember, our patient has an uncle and an aunt with diabetes. In my experience, most patients do not know whether their family history of diabetes refers to type 1 or 2. A quick phone call during the clinic visit can do wonders in clarifying this important history.
Still, approximately 90% of new type 1 diabetes cases are sporadic and not familial. His diabetes is worsening despite the intervention of effective treatments for type 2 diabetes. The next best course of action for this patient is to order a four-antibody panel to detect islet autoantibodies: insulin autoantibodies, glutamic acid decarboxylase autoantibodies, islet antigen 2 autoantibodies, and zinc transporter 8 autoantibodies.
Each of these autoantibodies can contribute to type 1 diabetes, and testing for all four increases the sensitivity of the evaluation for type 1 diabetes. I’ll address the diagnosis and early management of type 1 diabetes. in the next installment of this discussion, so please stay tuned. And thank you for participating!
COMMENTARY
Why Is This Patient’s Diabetes Getting Worse?
DISCLOSURES
| March 10, 2025This is a clinical scenario drawn from my own practice. I’ll tell you what I plan to do, but I’m most interested in crowdsourcing a response from all of you to collectively determine best practice. So please answer the polling question and contribute your thoughts in the comments, whether you agree or disagree with my approach.
The Patient
A 31-year-old man presents for follow-up regarding suspected type 2 diabetes. He had no symptoms at his wellness appointment 6 weeks ago, but his A1c level was elevated, at 6.8%. His fasting blood glucose at the time was 148 mg/dL and the rest of his laboratory work, including a comprehensive metabolic panel and lipid panel, was normal. All his laboratory work, including his A1c result, was normal 3 years ago. Of note, the patient reports that he has an uncle and an aunt with diabetes.
After receiving the call about his elevated A1c, the patient changed his diet and started jogging again after 5 years of sedentary behavior. Still, he is interested in medication to treat his obesity (body mass index, 31; waist circumference, 130 cm) and suspected case of diabetes. He agrees to start semaglutide at 0.25 mg once a week for the first 4 weeks.
During a telehealth appointment 1 month after treatment initiation, the patient is excited to report that his lifestyle regimen plus semaglutide have resulted in a weight loss of 5 kg. He does feel more tired, but he attributes this fatigue to his new exercise regimen. At this visit, his semaglutide dose is increased to 0.5 mg.
The patient undergoes another round of blood work 2 months later. Now the labs indicate that his A1c has actually risen, to 7.7%. The patient is frustrated because he has continued to lose weight and has adhered to his regimen of behavioral changes and pharmacotherapy. His fasting blood glucose at home is consistently higher than 150 mg/dL.
Dr Vega’s Take
The answer, dear reader, is choice 2: check for islet cell autoantibodies. I have hundreds of patients with diabetes in my practice, and although every patient is quite unique, there are clearly defined patterns to the disease course of type 2 diabetes. The vast majority of patients with type 2 diabetes have overweight or obesity and often have additional metabolic abnormalities, such as hypertriglyceridemia or metabolic dysfunction–associated steatotic liver disease, at the time of diagnosis.
However, there are times when a patient’s type 2 diabetes disease pattern does not align with what we commonly recognize or expect. This patient’s case is a prime example: He is taking a highly effective medication (semaglutide) and following behavioral recommendations, yet his A1c level is worsening.
One key tenet I have learned again and again in clinical practice is to take the time (I know, no one has enough of it!) to step back and reevaluate my presumptions when a case veers off the typical path. For this patient, once I considered the fairly rapid degradation in glycemic control with weight loss in the setting of an effective treatment for type 2 diabetes, the possible etiology became clear: type 1 diabetes.
There are many reasons why type 1 diabetes might not have been initially considered in this case. First and foremost, 90%-95% of all diabetes cases in the United States are type 2. Plus, the prevalence of type 2 diabetes keeps rising — especially among adolescents and young adults. As clinicians, we are more inclined to diagnose type 2 vs type 1 diabetes, given that we see so many more cases of type 2 diabetes.
But isn’t this 31-year-old patient too old to develop type 1 diabetes? Actually, although the incidence rate of type 1 diabetes in the United States is highest among 10- to 14-year-old children, incident cases among US adults are higher relative to children and adolescents. It’s simple math: There are many more adults than children, and type 1 diabetes can be diagnosed at any age.
Risk factors for type 1 diabetes include a family history of type 1 diabetes and a personal or family history of autoimmune conditions such as thyroiditis, celiac disease, or vitiligo. Remember, our patient has an uncle and an aunt with diabetes. In my experience, most patients do not know whether their family history of diabetes refers to type 1 or 2. A quick phone call during the clinic visit can do wonders in clarifying this important history.
Still, approximately 90% of new type 1 diabetes cases are sporadic and not familial. His diabetes is worsening despite the intervention of effective treatments for type 2 diabetes. The next best course of action for this patient is to order a four-antibody panel to detect islet autoantibodies: insulin autoantibodies, glutamic acid decarboxylase autoantibodies, islet antigen 2 autoantibodies, and zinc transporter 8 autoantibodies.
Each of these autoantibodies can contribute to type 1 diabetes, and testing for all four increases the sensitivity of the evaluation for type 1 diabetes. I’ll address the diagnosis and early management of type 1 diabetes. in the next installment of this discussion, so please stay tuned. And thank you for participating!
Any views expressed above are the author's own and do not necessarily reflect the views of WebMD or Medscape.
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