The different forms
of diabetes no longer lend them selves to two simple categories.
Various efforts to refine the classification have been met with
controversy and complicated by evolving understanding. Here is my
attempt to summarize the current thinking.
Type 1: caused by
complete autoimmune destruction of the beta cells. A good practical
definition is that patients require exogenous insulin in order to
stay alive. That is, they will invariably develop ketoacidosis (DKA)
when deprived of insulin, even in the basal state.
It is important to specify
the basal state, because patients with other forms of diabetes can go
into DKA as well, but only in the presence of some stressor such as
sepsis, MI, stroke, etc. This
designation has changed little in recent decades and remains useful,
though it has seen some tweaks as noted below.
Type 1b aka 1.5: These
designations are no longer very
useful for a variety or
reasons. They originally
(especially 1b)
referred to a group of patients in certain ethnic groups with
phenotypic characteristics of both type 1 and type 2 diabetes who
seemingly transitioned from type 1 to type 2 and/or back, due
to a non autoimmune mechanism: intermittent reversible severe beta
cell failure due to an exaggerated form of glucotoxicity. This
group has subsequently been found to be more heterogeneous than
previously thought, both in terms of ethnicity and pathogenesis. To
confuse things further, these terms (especially
1.5) have also been used to
denote late autoimmune diabetes of adulthood (LADA), an unrelated
condition. The terms were partially
replaced in popular usage with ketosis prone type 2 diabetes but
that too has been waning in
popularity, largely
abandoned. The ADA,
recognizing that there are patients who develop DKA but lack
antibodies, created the category of “idiopathic type 1 diabetes.”
A more recently proposed
category recognizes the heterogeneity in these patients (and
subclassifies them accordingly) and is known as ketosis prone
diabetes (see below). To
confuse things a bit, KPD also incorporates patients who do not fit
this phenotype, in order to
encompass all diabetic patients who go into ketoacidosis apart from
some severe stress.
(Note: a very early designation for
patients seemingly transitioning between the phenotypes of DM 1 and 2
was Flatbush diabetes).
Ketosis
prone diabetes (KPD): This is a proposed designation to replace
the category immediately above and
adds some other mechanisms,
attempting to encompass all patients who spontaneously develop DKA.
It recognizes the heterogeneity of the phenotype above,
specifically the fact that
some forms have an autoimmune pathogenesis. Its
4 categories are based on the presence or absence of beta cell
reserve and the presence or absence of autoimmunity.
Type
2: DM 2 is pretty well defined and I will not spend a great deal of
time here other than to caution against defining it as any case of
diabetes that does not develop DKA in the basal state. That is to
say that some forms of diabetes, that don’t invariably cause DKA in
the basal state, are not appropriately classified as DM 2 as will be
discussed below. Although DM
2 is itself heterogeneous the patients have in common insulin
resistance, gradual beta cell fatigue and the metabolic syndrome.
Type
3: Here’s where it gets
even more confusing. While
often a wastebasket there are some forms of diabetes that rightfully
belong in this category though in current literature they have varied
and sometimes quite limited degrees of acceptance. There are
numerous subcategories. Here they are.
Type
3, no letter designation: This is a theoretical construct that Alzheimer
disease is essentially diabetes (insulin resistance) localized to the
brain and might be effectively treated with insulin sensitizing
agents.
Additional
categories of DM 3, designated by letter, were taken from this site:
Type 3 A refers to
genetic defects in beta cells, essentially MODY. Inheritance is
monogenic autosomal dominant as opposed to the polygenic inheritance
of DM 2.
Type 3 B refers to
severe genetically determined insulin resistance as seen in Donohue syndrome and related disorders.
Type 3 C is a more
accepted category and denotes diabetes due to damage to the pancreas
as a whole, eg pancreatitis, pancreatic cancer or pancreatic trauma.
[1] [2]. This is important because it is usually
misdiagnosed as DM 2 yet has unique treatment implications.
Type 3 D is DM
caused by other endocrinopathies eg Cushing’s.
Type 3 E refers to
DM caused by drugs such as corticosteroids.
Type 3 F refers to
DM caused by infection. In the cite referenced above congenital
rubella was given as the example. Would Hep C fit in here?
Type 3 G refers to
diabetes associated with unusual autoimmune diseases, eg stiff person
syndrome.
Type 3 H refers to
diabetes associated with Down’s syndrome.
Note: Although all
the entities mentioned above under type 3 are real I could find
little or no independent support in the literature for the
nomenclature except for the one with no letter designation
(Alzheimer disease) and type 3C.
Type 4 This is a
theoretical construct based on an animal model, attempting to
explain some instances of apparent DM 2 in lean adults. This may not
be an important entity in man if it exists at all and might be
confused with LADA.
Miscellaneous forms:
Latent autoimmune
diabetes in adults (LADA). It is sometimes been referred to as DM
1.5.
Double diabetes.
You could be unlucky and have both 1 & 2. Or, in DM 1, if you
treat overeating with more and more and more insulin and thereby gain
of sufficient weight the characteristics of DM 2 could develop
secondarily.
