Ketosis-Prone Diabetes

Does presenting with diabetic ketoacidosis (DKA) mandate indefinite insulin treatment? Not always. Since the mid-1990s, we’ve increasingly observed and recognized patients that don’t neatly fit into either type 1 diabetes (T1DM) or T2DM. Ketosis-prone type 2 diabetes mellitus (KPDM) is underrecognized and distinctive. First described by Winter and colleagues in 1987, 12 African-American patients initially presented with DKA, but their disease course unfolded more like that of an individual with T2DM.¹ KPDM was initially thought to be a variant of maturity onset diabetes of the young (MODY). Other names include Flatbush diabetes (named for the part of Brooklyn, NY where young African-Americans were described to have these clinical features of KPDM), type 1.5 diabetes, and atypical diabetes. 

Here are some helpful clinical pearls.

1. A large number of KPDM patients present without a previous diagnosis of DM and without a known precipitating cause for the DKA.

>75% of KPDM patients fit this description. Most patients are African-American or Hispanic, overweight or obese, male (there’s a two- to three-fold greater prevalence in men compared with women), in their 40s or 50s at the time of diagnosis.

2. If the patient’s insulin requirements rapidly decline in the first several weeks after presenting, think of possible KPDM.

Smiley and colleagues² recommend that:

i. Patients test pre-meal glucose at least 2 times/day, and check in with their health care professional team every 2 weeks for the first 2 months after being discharged from the hospital to titrate insulin, and subsequently every 2 or 3 months, as extent of control warrants.

ii. Clinicians begin tapering insulin by 25% at each visit, once fasting glucose declines below 130 mg/dL for 2 weeks, or if the patient develops hypoglycemia.

3. Many patients with KPDM will spontaneously remit.

Most patients can discontinue insulin by 12 weeks post-discharge. While most meet the definition of remission (a hemoglobin A1c <7% and a fasting glucose <130 mg/dL that persists after being off insulin), about 70% may cycle between relapsing and remitting within 2 years after being diagnosed with KPDM. Studies have examined the role of oral antihyperglycemic agents, such as glipizide.³ One study at Emory was completed recently comparing metformin and sitagliptin on preserving remission.

To go from needing insulin when first diagnosed with diabetes, to not requiring this medication at all in a matter of months, would appear to be very unusual and highly counterintuitive. KPDM reminds us that some patients defy ready classification into broad, established categories -- that medicine is constantly evolving, and, in the words of one of my mentors, Dr. Daniel Porte, “Life often gets more complicated.”

References:

1. Winter WE, et al. Maturity-onset diabetes of youth in black Americans. N Engl J Med. 1987;316(6):285-291.

2. Smiley D, et al. Update on diagnosis, pathogenesis and management of ketosis-prone Type 2 diabetes mellitus. Diabetes manag (Lond). 2011;1(6):589-600.

3. Banerji MA, et al. Prolongation of near-normoglycemic remission in black NIDDM subjects with chronic low-dose sulfonylurea treatment. Diabetes. 1995;44(44):466-470.