1. Strategies for the Practical Management of Type 2 Diabetes
Aaron Vinik MD, PhD, FCP, MACP, FACE
Murray Waitzer Endowed Chair for Diabetes Research
Professor of Medicine, Neurobiology and Pathology
The Leonard Strelitz, Diabetes and Metabolic Institute
Neuroendocrine Unit, Norfolk VA 23510
3/20/16

2. Contents Physiology and pathophysiology of type 2 diabetes
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Contents
Physiology and pathophysiology of type 2 diabetes
Role of Incretins, DPP IV inhibitors, SGLT 2, inhibitors,
How intensively should we treat and are there problems
Contents
Now we will discuss the role of incretins.

3. diagnosed–leading to rises in fasting and postprandial glucose levels.
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Development and Progression of Type 2 Diabetes
Speaker notes
This conceptual diagram shows a recently proposed paradigm on the development and progression of pathophysiology in type 2 diabetes.
The horizontal axis in the figure shows the years from diagnosis of diabetes.
Insulin resistance rises during disease development and continues to rise during impaired glucose tolerance (IGT). Over time, insulin resistance remains stable during the progression of type 2 diabetes.1,2
The insulin secretion rate increases, to compensate for the decrease in insulin effectiveness due to insulin resistance. This increase is often misperceived as an increase in beta-cell function. Thus, beta-cell function can decrease even as insulin secretion increases. Over time, beta-cell compensatory function deteriorates and insulin secretion decreases. Beta-cell function progressively fails.
Initially, fasting glucose is maintained in near-normal ranges. The pancreatic beta cells compensate by increasing insulin levels, leading to hyperinsulinemia. This compensation keeps glucose levels normalized for a time, but as beta cells begin to fail, IGT develops with mild postprandial hyperglycemia. As the disease progresses, the beta cells continue to fail, resulting in higher postprandial glucose levels. With further loss of insulin secretory capacity, fasting glucose and hepatic glucose production increase.
Once beta cells cannot secrete sufficient insulin to maintain normal glycemia at the fasting or postprandial stage, type 2 diabetes (hyperglycemia) becomes evident.
Insulin resistance and beta-cell dysfunction are established well before type 2 diabetes is diagnosed.1,3
Purpose:
To address the common misconception that an increase in insulin secretion (hyperinsulinemia) connotes an improvement in beta-cell function.
Takeaway:
Both insulin resistance and beta-cell dysfunction start early–and well before diabetes is
diagnosed–leading to rises in fasting and postprandial glucose levels.
References
1. Ferrannini E. Symposium: When does hyperglycemia become diabetes? Impaired β-cell function. Presentation at 65th ADA in Washington, DC, Available at Accessed October 2006.
2. Ramlo-Halsted BA, Edelman SV. The natural history of type 2 diabetes. Implications for clinical practice. Prim Care. 1999;26:771–789.
3. Kahn SE. The relative contributions of insulin resistance and beta-cell dysfunction to the pathophysiology of type 2 diabetes. Diabetologia. 2003;46:3–19.

4. Insulin and appetite interact in the brain when neurotransmitters in the hypothalamus signal satiety in response to increased insulin.
Adding brain and neurotransmitter dysfunction to the pathogenic picture of type 2 diabetes gives us the ominous octet. 4

5. 5/11

6. Too Many Notes: Up and Down the Scales of Diabetic Therapy
Aaron Vinik MD Guest Editor;
Clinical Therapeutics 29: 1227, 2007

7. “All who drink of this treatment recover in a short time
“All who drink of this treatment recover in a short time. Except for those who died. Thus, it appears to be effective in all but the incurable cases.”
Galen

8. Patient-Centered Care

9. Modern Antihyperglycemic Agents

10. Failure to Achieve Goals
Complex disease; Difficult lifestyle
Natural progression of disease
Low health literacy/ lower social strata
Multiple medications – costs associated
Lack of suppression of Glucagon
Drug side effects
Weight gain
Hypoglycemia
GI side effects
Change in blood pressure
Cardiovascular safety
Restricted use (Elderly, CHF, Renal Impairment)
Failure of health professionals

12. “I don’t want to make the wrong mistake.”
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“I don’t want to make the wrong mistake.”
Y Berra