Table 7 |
|
|
The Five Stages of T2DM: |
|
| The Natural Progressive History of T2DM. |
|
| I. |
LATENT STAGE:[EARLY] |
| Insulin Resistance: |
|
| Genetic Component |
|
| Environmental component. Modifiable: obesity/sedentary life style. Nonmodifiable:
aging |
|
| Beta Cell Defect: (Dysfunction) |
|
| Genetic ....... Abnormal processing, storage or secretion. |
|
| Intracellular/extracellular oligomers of Islet Amyloid toxicity to the Beta Cell.
Abnormal processing, storage or secretion |
|
| Islet Amyloid: Diffusion Barrier: Secretory Defect: Intra Islet Absorptive Defect: |
|
| II. |
TRANSITION STAGE:[MIDDLE] |
| Persistent Hyperinsulinemia, Hyperproinsulinemia. → Ang II Accelerated Atherosclerosis |
|
| Persistent Hyperamylanemia. → AngII Accelerated Atherosclerosis |
|
| Continued remodeling of the endocrine pancreas (amyloid). |
|
| Beta cell displacement, dysfunction, mass reduction due to the toxic effect of IAPP
oligomers and the progressive developing diffusion barrier. |
|
| III. |
IGT STAGE (Impaired Glucose Tolerance):[LATE] "Pre-diabetes" Human Health Services (HHS) and American Diabetes Association (ADA)
term. |
| [Start treatment at this time] |
|
| Diagnose earlier: rejuvenation of the 2 hour glucose tolerance blood sugar 140–199
mg/dl |
|
| Increased insulin resistance [Feeds forward] > Glucotoxicity [Feeds forward] > Insulin
resistance [Feeds forward] > Glucotoxicity: creating a vicious cycle. |
|
| Islet amyloid. Increasing beta cell defect. Loss of beta cell mass with displacement.
(Remodeling of islet architecture including extracellular matrix). Beta cell loss
centrally. |
|
| IV. |
IFG STAGE (Impaired Fasting Glucose):[LATER] "Pre-diabetes" Human Health Services (HHS) and American Diabetes Association (ADA)
term. |
| Blood sugar ranging [110–125 mg/dL] |
|
| *ADA new cut point IFG Nov 2003: [100–125 mg/dl] |
|
| Impaired hepatic glucose production: Increasing global insulin resistance (hepatic) with subsequent gluconeogenesis. Feeding
forward in the vicious cycle to accelerate insulin resistance globally. |
|
| V. |
OVERT STAGE:[TOO LATE] FBG 126 or greater: Random or 2 hour OGTT 200 or > |
| [50% loss of beta cell function at the time of clinical diagnosis] |
|
| Use medications that do not increase endogenous insulin or amylin. Use combination
therapy. Start treatment at stage III-IV (IGT-IFG). |
|
| . |
Paradigm Shift. → Diagnose Early → Start treatment Early → Stage III: IGT. |
|
|
|
|
Hayden and Tyagi Nutrition Journal 2004 3:4 doi:10.1186/1475-2891-3-4 |
|
