“Natural
History of Type 2 Diabetes” is the heading of the first section of a scientific
paper by Ralph A. DeFronzo, M. D. The full text can be found on the PubMed site
here. It was
also the basis of his Banting award lecture at the 2008 annual meeting of the
American Diabetes Association in San Francisco. This paper caught my attention
for the statement (cited in The Nutrition Debate #86 here)
in which Dr. DeFronzo says in the section under Prediabetes, “In summary,
individuals with IGT [impaired glucose tolerance] are maximally or
near-maximally insulin resistant, they
have lost 80% of their β-cell
function, and they have an approximate 10% incidence of diabetic
retinopathy. By both pathophysiological and clinical standpoints, these pre-diabetic individuals with IGT
should be considered to have Type 2 diabetes” (emphasis mine).
Dr. DeFronzo
is using the medical phrase “natural history” to describe the progression of a
disease from incidence to full-blown diagnosis. In this blog I will comment on
quotes from this “history” section of Dr. DeFronzo’s paper to explain this
progression and attempt to simplify the language to make it more user-friendly
for the lay reader. I think his expert exposition of the stages of development
of Type 2 diabetes is so important that it is worth the slog. Dr. DeFronzo’s
point is that we need a “new paradigm” of early intervention: “The clinical
implications of these findings for the treatment of Type 2 diabetes are that
the physician must intervene early, at the stage of IGT [impaired glucose
tolerance] or IFG [impaired fasting glucose].The main thrust of his
presentation is that we need a “new paradigm”
where “the physician must intervene early.” In writing this blog
primarily for “patients” and other individuals who may have IGT or IFG, it is
my hope that they will see the
need to “intervene early” as well. It is much easier to control blood sugar if
you have some remaining beta cell function.
DeFronzo
begins, “Individuals destined to develop Type 2 diabetes inherit a set of genes
from their parents that make their tissues resistant to insulin.”(I don’t think
the gene set is definitively known yet, but it surely will be soon.) “In liver, the insulin resistance is
manifested by an overproduction of glucose during the basal state despite the
presence of fasting hyperinsulinemia and an impaired suppression of hepatic
glucose production in response to insulin, as occurs following a meal.” (The
liver overproduces glucose when we are in the fasting state despite low blood
insulin levels. That is why physicians now usually prescribe Metformin first to
both suppress this glucose production -- called gluconeogenesis – and improve
insulin sensitivity.)
“In muscle,
the insulin resistance is manifest(ed) by impaired glucose uptake following
ingestion of a carbohydrate meal and results in postprandial hyperglycemia.”
(Interesting. It’s the muscles.) “Although the origins of the insulin
resistance can be traced to their genetic background, the epidemic of diabetes
that has enveloped westernized countries is related to the epidemic of obesity
and physical inactivity. Both obesity and decreased physical activity are
insulin resistant states and, when added to the genetic burden of insulin
resistance, place a major stress on the pancreatic β-cells to augment their
secretion of insulin to offset the defect in insulin action.” (So, insulin
production increases to deal with the combination of elevated levels of
circulating glucose and our impaired insulin action due to insulin resistance.)
“As long as
the β-cells
are able to augment their secretion of insulin sufficiently to offset the
insulin resistance, glucose tolerance remains normal.” (So, we have two faulty mechanisms at work here yet our blood
glucose levels in response to both fed and fasting states are still normal.)
“However, with time the β-cells begin to fail and initially the postprandial plasma
glucose levels and subsequently the fasting plasma glucose concentration begins
to rise, leading to the onset of overt diabetes.” (Note that postprandial blood sugars rise first, then later
fasting blood glucose.) That is the reason that the HbA1c
test is rapidly replacing the fasting blood glucose test. The HbA1c
test measures the average of all blood glucose values over a 3-month period and
thus captures the elevated postprandial values in the average, whereas
obviously the fasting blood glucose test does not. Ask your doctor to do an HbA1c
test! An A1c over 5.5 indicates an increased risk for heart disease. In the
U.S., if you have indications of Metabolic
Syndrome, your insurance should pay for 4 tests per year.)
“Collectively,
the insulin resistance in muscle and liver and β-cell failure have been
referred to as the triumvirate. (This is again a reference to part of the title
of Dr. DeFronzo’s presentation.) “The resultant hyperglycemia [elevated blood
glucose] and poor metabolic control may cause further decline in insulin
sensitivity, but it is the progressive
β-cell failure that determines
the rate of disease progression.”
Dr. DeFronzo’s paper then continues to describe his
own research into the β-cell failure rate in detail but let this
suffice: “Although the plasma insulin response to the development of insulin
resistance typically is increased during the natural history of Type 2
diabetes, this does not mean that the β-cell is functioning normally. To the contrary,
recent studies from our group have demonstrated that the onset of β-cell
failure occurs much earlier and is more severe than previously appreciated.” That frightening statement is in pretty plain
English. I don’t think it requires any interpretation on my part.
Fantastic article, Dan. I appreciate Dr. De Fronzo's explanation of insulin resistance leading to beta cell failure. I'm often amazed that many health practitioners aren't aware of the risks related to high postprandial BG in prediabetes. As long as the fasting BG is below the level diagnostic for DM, they tell the patient they're "borderline." Meanwhile, the person may be sustaining damage to their blood vessels, nerves, and organs. Maintaining postmeal blood sugars under 140 (preferably lower) should be the goal for anyone wanting to avoid such complications.
ReplyDeleteThanks, Franziska. I afraid I am more cynical that you are, or can express, given that you are a health practitioner. I would say 'most,' even 'vast majority,' rather than many health practitioners..., but can afford to be impolitic.
DeleteI am inclined to think that pressures like 'standards of practice' and Medicare and insurance company reimbursement policies interfere even with those who would inform themselves of the current state of knowledge. Most practitioners still get their CEU credits at CDE educator seminars and AHA and ADA conventions, periodical and newsletters, etc., so they are oblivious to the cutting edge stuff. My doctor, who diet a few weeks ago, had very little to lose when he suggested I try Atkins Induction 10 1/2 years ago. He only read about it in the NYT Sunday Magazine cover story by Gary Taubes, "What If It's All Been a Big Fat Lie." He was a cardiologist but he was tempted by the ribeye steak on the cover photograph and tried it himself -- with no ill effects. So much for professional education! Thanks for commenting.
Readers might be interested in Franziska's website and blog: http://www.lowcarbdietitian.com/blog.html