See ya LADA, alliGADa!

A few weeks ago I saw on referral a very pleasant 76-year-old woman with diabetes who had not done well on oral therapy and was having great trouble adjusting to insulin therapy given as glargine every night at bedtime. More specifically she was having very wide fluctuations in capillary blood glucose from ~500 mg/dL at the high end and 30-40 mg/dL at the low end. These symptomatic hypoglycemic episodes occurred in the early hours of the morning, and she was too disorientated to really care of herself.

Her devoted son moved in with her and kept an almost night-long vigil, giving her large doses of orange juice whenever she experienced this hypoglycemia. On the first episode he witnessed, he checked her CBG at 35 mg/dL before giving the juice but on subsequent occasions was astute enough to recognize the symptoms and give orange juice without taking time to check the CBG.

The problem arose when she would wake up in the morning and her CBG would be quite high, occasionally above 500. The regimen was changed to glargine at bedtime premeal rapid-acting insulin based on her premeal CBG — the so-called “sliding scale.” She also continued to take metformin 1,000 mg twice per day.

When I first saw her as a patient, she was feeling well but frustrated by these wide swings in her glucose. She carried a diagnosis of type 2 diabetes, made on the basis of random blood glucose obtained at a routine clinic visit. She had no symptoms related to her diabetes at this initial diagnosis, no family history of diabetes and no history of pancreatitis. Her weight was (and is) 136 lb, and she was 65” tall. There was no history of cardiac or other vascular disease; her estimated glomerular filtration rate was 65 mL/min/1.73 m², electrolytes were normal, but she was anemic at 9.3 g/L.

Over the next several days, she and I were in frequent phone contact as we worked together to minimize the wide fluctuations in blood glucose using glargine and rapid-acting insulin with meals. One morning, she was rushed to the ER quite obtunded with a CBG of 27 mg/dL. She recovered quickly but was hospitalized briefly because her hemoglobin was down to 7.3 and she required transfusion.

At the first outpatient visit, the possibility was considered that she did not have type 2 diabetes as one would expect with this age of onset but in fact had type 1 diabetes. Her C-peptide level was low, but that had limited meaning given that she was treated with insulin. Insulin antibodies were not detected but glutamic acid decarboxylase antibodies were present and elevated.

The correct diagnosis in this patient is latent autoimmune diabetes in adults (LADA), which I wrote a blog about some time ago. There are several other autoimmune diseases that can be associated with LADA, often predating the diagnosis of diabetes. Hypothyroidism is perhaps the most common of these, and with a thyroxine of 0.6 and a thyroid-stimulating hormone of 4.5, antibody studies are pending. Her anemia is also autoimmune related as the in-hospital evaluation confirmed that the etiology of the anemia was vitamin B12 deficiency.

Hindsight is 20/20 vision, and the real clue to this patient’s correct diagnosis was the wide fluctuations in CBG when insulin was started. This patient was clearly telling us that she did not have insulin resistance!