Dan-Crowe-LADA-slides

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The Old Paradigm
• Type 2 diabetes- Insulin resistance leads to pancreatic
decline in insulin secretion.
• Think “Adult- Onset Diabetes Mellitus”. Still produce insulin, but
not enough (C-peptide +), not prone to DKA (Ketone -)
• Type 1 diabetes- Autoimmune attack on pancreatic
beta-cell leads to complete loss of insulin secretion and
to lifelong insulin-dependence
• Think “Juvenile Diabetes”.
No insulin
production (C- Peptide -), thus prone to DKA (Ketone +).
The New Paradigm
The Key Questions:
• Phenotype- Non-obese vs. Obese?
• Ketones?
• C-peptide present?
• Auto-antibodies present (GAD-65, Islet Cell
Ab)?
2 Fasting BG’s >100 mg/dll
Two 2 hr GTT >200 mg/dl
Classic Poly’s + random BG >200 mg/dl
A1c>6.5%????
Obese Phenotype
Non-Obese Phenotype
Ketosis-Prone?
Ketones C-Peptide +
YES
C-peptide ?
Ketones+
C-peptide+
Ketones +
C-Peptide -
No:
Type 1 diabetes
70% have autoantibodies
(GAD-65, Islet Cell Ab)
~50% of Type 1 diabetes occurs
After age 40 with another peak
In the 70’s-80’s.
Ketones +
C-Peptide -
No:
Non-obese Type 2
(~15% of Type 2’s)
Ketones+
C-peptide+
Yes:
Ketosis-Prone Diabetes
AKA “Flatbush Diabetes”
Most can be treated with OHA or
OHA plus Insulin
OR
Latent Autoimmune Diabetes of the Adult
Or LADA
Autoantibodies Present (GAD-65, Islet cell Ab)
Treat as Type 2 but test C-peptide periodically
As they will become Type 1 C-peptide negative
Type 1
diabetes
with
Type 2
Phenotype
Ketones C-Peptide +
Type 2 diabetes
85% of Type 2’s
Non-Obese Phenotype
•Non-obese Type 2 Diabetes- ~3.5 million Americans
KetoneC-peptide+
treat like other Type 2 diabetes patients
•Type 1 Diabetes- 1-1.5 million Americans
Ketone +
C-Peptide 70% Auto-antibody +
life-long insulin-dependence
•Ketosis-prone Diabetes
Ketone +
C-peptideMost can be treated with OHA or OHA+Insulin
•Latent Autoimmune Diabetes of the Adult-LADA
Ketones +/C-peptide +
Auto-antibodies +
Will likely eventually transition to C-peptide - Type 1 diabetes
Obese Phenotype
•Type 2 Diabetes- the vast majority of your patients
KetoneC-peptide +
85% of Type 2’s
D/E, Oral agents, Incretins, Insulin
•Type 1 with Type 2 Phenotype
Ketone +
C-Peptide Intensively-treated Type 1’s with genetic predispostion to central
obesity and insulin resistance
Life-long insulin dependence; consider Pramlintide
•Ketosis-Prone Diabetes
Ketone +
C-peptide+
To Confuse the Picture
Glucotoxicity- inhibition of insulin secretion
due to prolonged exposure to high-levels of
glucose; can be Ketone +, C-peptide -. Intensive
treatment allows pancreatic insulin secretion to
resume.
Lipotoxicity- inhibition of insulin secretion due
to prolonged exposure to high-levels of
circulating fatty acids
Type 1 diabetes
70% have autoantibodies
(GAD-65, Islet Cell Ab)
~50% of Type 1 diabetes occurs
after age 40 with another peak
in the 70’s-80’s.
OR
Latent Autoimmune Diabetes of the Adult
Or LADA
Autoantibodies Present (GAD-65, Islet cell Ab)
Treat as Type 2, but test C-peptide periodically
as they will become Type 1 C-peptide negative

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