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This article originally posted 13 June, 2011 and appeared in  ObesityMedicationType 2 DiabetesGLP-1 Series Issue 2GLP-1

A 25-year-old Hispanic woman with a 5-year history of type 2 diabetes

A 25-year-old Hispanic woman with a 5-year history of type 2 diabetes presents for a routine follow-up visit. Despite education, she has had difficulty making diet and lifestyle modifications and currently has a BMI of 45 kg/m2....

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Her treatment advanced from monotherapy with metformin at initial diagnosis, to her current regimen of metformin 2000 mg, glimepiride 8 mg, and sitagliptin 100mg daily. She performs home blood glucose monitoring and her fasting blood glucose levels range between 120 and 150 mg/dL. She experiences symptoms of hypoglycemia very rarely, only once every few months. Her A1C level is 7.8% and a recent fasting c-peptide level was 6 ng/mL (normal range 0.78-1.89 ng/dL). The patient is concerned that her medication is not working as well as it should. Although her mother has type 2 diabetes, a nephew has type 1 diabetes, and she is wondering if she could have type 1 diabetes instead of type 2. 

The patient’s glycemic control remains unacceptable (A1c >7%) with triple oral antihyperglycemic medication therapy just 5 years after diagnosis of diabetes. It is important to identify which type of diabetes this patient is experiencing, to optimize her treatment. Favoring type 1 diabetes (in the slow-to-develop form known as latent autoimmune diabetes in adults or LADA) is the relatively early failure of oral therapies and the presence of type 1 diabetes in her family history. Favoring type 2 diabetes is her very high BMI and the presence of type 2 diabetes in a close relative. It is possible to have true type 1 diabetes together with features of type 2 diabetes (e.g. obesity and insulin resistance). When this occurs, the presence of a high c-peptide level may not exclude type 1 diabetes, with autoimmune injury to the beta cells, and a need for insulin treatment. The high c-peptide level, however, does suggest quite significant resistance to the action of insulin.

Anti-Gad testing was performed; in this case, and was found to be negative. 

Your recommendation?
1. Refer to dietitian for a weight loss program
2. Start on Lantus Therapy
3. Start on a TZD
4. Reduce the glimepiride and begin liraglutide
 
Answer and Critique (Correct Answer = 4)

Recommendations:  A good test to make the distinction between type 1 and type 2 diabetes in this patient would be measurement of anti-GAD antibodies. If anti-GAD antibody levels are positive, type 1 diabetes would be probable and insulin would be the preferred next therapy. If anti-GAD antibody tests are negative, other treatments could be considered. Liraglutide, a GLP-1 receptor agonist, would be a good choice, as it can cause sustained loss of weight as well as improved control of postprandial hyperglycemia. Because this patient’s fasting glucose is not very high, a significant contribution to her high A1C is from postprandial hyperglycemia, which could respond well to liraglutide. However, insulin is more reliably effective than liraglutide when A1C levels are quite high (e.g. above 8.5%). Another alternative, a thiazolidinedione, is less attractive in this patient because of its strong tendency to cause weight-gain. 

Key Point:

  • Anti-GAD antibody testing should be considered in patients previously diagnosed with type 2 diabetes who advance to insulin therapy more rapidly than expected, to rule out latent autoimmune diabetes in adults (LADA).
  • The GLP-1 receptor agonist liraglutide is an option for patients failing oral therapy who have an elevated BMI, if the A1C is not too high (A1C <8.5%). 
  • Lifestyle modifications should be encouraged regularly, even if the patient has previously failed at modifying diet and exercise habits.

In this case, anti-GAD testing was performed and was found to be negative. The patient returned for another follow-up visit and it was explained that her original diagnosis of type 2 diabetes was accurate. It was decided that insulin treatment was not necessary at this time since her A1C was 7.8% and she expressed motivation to improve her diet and activity level. She continued on her metformin 2000 mg daily but her glimepiride was reduced to 4 mg daily, which is considered a maximally effective dose. She was started on liraglutide 5 μg twice daily and taught how to administer it by injection. She was also given a prescription to advance the dose to 10 μg in four weeks if her starting dose was well tolerated. The sitagliptin, a DPP-4 inhibitor, was discontinued since it works by a similar mechanism as liraglutide but may be less effective at reducing postprandial hyperglycemia. While sitagliptin does not promote weight gain, it will not help with weight loss, which is one of this patient’s goals. The patient is scheduled for another follow-up visit and at that time, if her A1C is still above 7%, then initiation of insulin will be considered.

Rationale: Although insulin would be effective in rapidly improving this patient’s glycemic control, it would likely lead to weight gain. Once a diagnosis of type 2 diabetes was confirmed, other treatment options could be considered. This patient was young at the time of diagnosis and is now more mature and willing to consider lifestyle modifications. Liraglutide may promote weight loss to help encourage the patient in her lifestyle changes, and it is likely to be more effective than basal insulin in reducing her postprandial hyperglycemia. 

References:
  1. Heine RJ, Van Gaal LF, Johns D, et al. Liraglutide versus insulin glargine in patients with suboptimally controlled type 2 diabetes: a randomized trial. Ann Intern Med. 2005;143:559-569
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This article originally posted 13 June, 2011 and appeared in  ObesityMedicationType 2 DiabetesGLP-1 Series Issue 2GLP-1

Past five issues: Issue 744 | Diabetes Clinical Mastery Series Issue 203 | Issue 743 | Diabetes Clinical Mastery Series Issue 202 | SGLT-2 Inhibitors Special Edition August 2014 |


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