1. β-Cell Centric Classification of Diabetes:
Implications for Classification, Diagnosis, Prevention, Therapy, Research
INSULIN** RESISTANCE
Environment* G E N E
Epigenetics
Inflammation/
Immune Regulation
Polygenic
Monogenic
β-Cell
secretion/mass
FINAL COMMON
DENOMINATOR
*Environment=Genetic suceptibility to
eg: viruses, endocrine disruptors, food AGEs, Gut Biome
**Insulin Resistance= Centrally Induced, Peripheral, Stress Hormones, Gut Biome

2. Primary Hyperinsulinemia- Genetic propensity( Corkey)
INACTIVITY,DIET
FFAs
INFLAMMATION, OXIDATIVE STRESS
INCREASED PAI-1,NFKB,MMPS,
ROS,AP-1,Egr-1

3. Hyperinsulinemia Early in Natural History of DM: ie: May Cause Diabetes by Causing Insulin Resistance in PI3 Kinase Pathway
But reduced insulin right after bariatric op- results in
Fast improvement in resolution of diabetic state
(PI-3 Kinase pathway, before IR improved
Pories WJ, MacDonald KG Jr, Morgan EJ, et al. Surgical
treatment of obesity and its effect on diabetes: 10-y followup.
Am J Clin Nutr 1992;55(2 Suppl):582S-5S.
Jimenez A, Perea V, Corcelles R, Moize V, Lacy A, Vidal J.
Metabolic effects of bariatric surgery in insulin-sensitive
morbidly obese subjects. Obes Surg 2013;23:

4. Potential Causes of Insulin Resistance and Their Interplay
Central IR
Loss of dopamine surge in SCN
increased appetite
Increased sympathetic tone
Hyperinsulinemia
Biome IR
Peripheral IR
Inflammation IR

5. Natural History of ALL DM
Age
Macrovascular Complications
Disability
IR Phenotype
MI CVA Amp
IGT ALL DM
DEATH
Blindness Amputation CRF
ETOH BP Smoking
Eye Nerve Kidney
Disability
Microvascular Complications
Risk of Dev. Complications 5

6. Genes,
Inflam
Envir
Hyperinsulinemia
FINAL
COMMON
DENOMINATOR

7. ARE THE SAME AS THOSE THAT DAMAGE THE Beta-Cell* * * *