MEDSCAPE

Ketosis-Prone Type 2 Diabetes

Author: Richard S Krause, MD; Chief Editor: George T Griffing, MD
Updated: Dec 20, 2013

Background
The original schema for classifying diabetes mellitus (DM) consisted of 2 categories
known as type 1 diabetes mellitus and type 2 diabetes mellitus. Type 1 diabetes
was also known as insulin-dependent diabetes. Patients with this type of diabetes
were considered prone to develop diabetic ketoacidosis (DKA).
Patients with type 1 diabetes were found to have an absolute insulin deficiency due
to autoimmune destruction of pancreatic beta cells. Patients with type 2 diabetics,
or noninsulin-dependent diabetes, were not considered to be at risk for DKA. Type 2
diabetes is strongly associated with obesity and a family history of diabetes. These
patients have peripheral insulin resistance with initially normal or elevated
circulating levels of endogenous insulin.
Pathophysiology
Since the mid-1990s, the number of patients who presented with DKA but did not
require long-term insulin therapy has increased. Many such patients had conditions
that resembled traditionally defined type 2 diabetes, in that they were obese and
often had a family history of diabetes. Subsequent to these observations, new ways
to classify diabetes were devised.
The system of classification that most accurately predicts the need for insulin
treatment 12 months after presentation with DKA is known as the A system. This
system classifies diabetics into 4 groups as follows:

A+- - Autoantibodies present, cell function absent

A++ - Autoantibodies present, cell function present

A-- - Autoantibodies absent, cell function absent

A-+ - Autoantibodies absent, cell function present

The commonest ketosis-prone diabetes (KPD) subgroup in a longitudinal study was

A-+ (54%), followed by A-- (20%) A+- (18%) and A++ (8%). [1] As noted above,
in the A-+ subgroup of patients with KPD cell antibodies are absent and cell
function is present. The triggering mechanisms leading to DKA in these patients are
not well defined. Viral infections, other metabolic factors such as oxidative stress
with concomitant G6PD deficiency, and genetic factors have been implicated.
Patients who are in the A++ and A-+ subgroups have clinical characteristics of
type 2 diabetes. The American Diabetes Association system classifies them as
having type 2 diabetes.[2] Patients with this metabolic and clinical profile who
experience DKA have ketosis prone type 2 diabetes.

Etiology
Ketosis-prone type 2 diabetes is prevalent in the United States among blacks and
Hispanics, who account for 20-50% of newly diagnosed patients. [3] Although
dependent on the baseline demographics of the study area, black ethnicity has
been noted in as many as 100% of cases of newly diagnosed type 2 KPD. As with
type 2 diabetes, most patients are obese and have a family history.
Prognosis
The long term prognosis of KPD varies with the A status. Patients who are require long term insulin therapy for glycemic control. Most patients in the A-+
subgroup have-long term remission (do not continue to require insulin) after
treatment of an initial DKA episode followed by a period of insulin therapy.
Patient Education
Patient education materials are available from various sources; an excellent
resource is the American Diabetes Association.