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March 07-08, 2019 | London, UK

Journal of Diabetology | Volume 3

Annual Summit on

Diabetes, Obesity & Heart

Diabetes, Endocrinology and Metabolic Syndrome

International Conference on

Joint Event

Why is hyperglycemia bad?

David W Moskowitz

GenoMed Inc., USA

ince the isolation of insulin from dog pancreases by banting

and best almost a century ago, treatment of diabetes has

focused on controlling glucose. It is generally assumed that

glucose’s effect is mediated through an increase in blood

osmolality and viscosity (PMID: 12871609), as occurs in the lens

of the eye. But blood viscosity increases only 5% when glucose

increases from 100 to 300 mg/dl. First, the 300% increase

must be divided by 18 for the molecular weight of glucose

(180g/mole), and, second, osmolality is due mostly to sodium

and chloride. Blood is essentially sea water, not lemonade.

There must be an amplification step, something beyond mere

osmolality/viscosity. One amplification step appears to be

ACE, which is activated by viscosity, since ACE appears to be

a mechanosensor (PMID: 12685804). But there’s another way

ACE is activated, even more strongly by glucose. ACE appears

to be glucose’s partner in a redox reaction (PMID: 15379656).

Raising glucose to 300mg/dl may increase osmolality by only

5%, but it should increase ACE activity one-for-one: for every

glucose molecule oxidized from an aldehyde to a carboxylic

acid, one active site of ACE is revealed. This appears to have

special importance for the kidney (PMID: 12396747) and lung

(PMID: 16510756); both organs sense oxygen levels. A corollary

is that a “normal” glucose level of 100 mg/dl is still chemically

active. Perhaps aging is due to glucose activation of ACE as redox

partners. Diabetes looks like accelerated aging because the

glucose level, and the amount of ACE activation, is increased. In

other tissues, like nerves, where ACE inhibitors have no effect,

glucosemay have unknown redox partners responsible for local

complications. We are still in the early steps of exploring this

hypothesis. My hope is that retinopathy will respond to high-

dose quinapril as diabetic kidney disease has done for the past

24 years. In summary, blocking glucose’s amplification partners

may be just as important clinically as controlling glucose.

Notes: