Re: The Ticking-Clock Hypothesis?

x-no-archive: yes

Larry wrote: 
Susan: I'll buy that if you say it COULD be sub-optimal. In Doctor talk
(I'm not) "normal" for a lab value means within normal range
established in the community.


Larry, I didn't know this was a negotiation!  :-)

"In the "community" diabetes and CVD *are* normal, so why aspire to it?

I can't say what you propose, because I don't believe it. A very large study of hundreds of Scandinavian men over 25 years time found that risk of death by heart attack increased 400% between the lowest quintile and the highest quintile of *normal* fasting blood glucose, with increased risk at every point between. (I can't find the cite, I wish I'd copied the article). Studies show that glucose tolerance worsens along the entire spectrum of the glucose continuum.

Here are a couple of cites I *can* put my hands on:

Blood Glucose Concentration Linked to>Cardiovascular Risk in Nondiabetic Men>
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WESTPORT,>CT (Reuters Health) Jan 04 - Increased glycated hemoglobin
(HbA1c)>concentrations are predictive of cardiovascular mortality among
all men,>not only those with diabetes, according to a report in the
British>Medical Journal for January 6.

Dr. Kay-Tee Khaw and colleagues, from>the University of Cambridge
School of Clinical Medicine, UK, collected>data on all-cause mortality
and cardiovascular mortality in 4662 men, 45>to 79 years of age, who
participated in the Norfolk UK cohort of the>European Prospective
Investigation into Cancer and Nutrition>(EPIC-Norfolk). At baseline,
from 1995 to 1997, HbA1c was measured and>the subjects were followed
until December 1999.

As expected, Dr.>Khaw's group found that diabetic men had increased
mortality for all>causes, cardiovascular disease and ischemic disease.
They also noted that>HbA1c concentrations were "continuously related to
subsequent all-cause,>cardiovascular, and ischemic mortality through
the whole population." The>lowest mortality rates were associated with
HbA1c concentrations below>5%.

Further, the group noted that a 1% increase in HbA1c was>associated
with a 28% increased risk of death, which was independent of>age, blood
pressure, cholesterol, body mass index and>smoking.

"Eighteen percent of the population excess mortality risk>associated
with a HbA1c concentration of 5% or more occurred in men with>diabetes,
but 82% occurred in men with concentrations of 5% to 6.9% (the>majority
of the population)," Dr. Khaw and colleagues point>out.

The researchers propose that an elevated concentrations of>HbA1c is a
marker for greater absolute risk among all men, and>"preventive
treatment with blood pressure- or cholesterol-lowering drugs>should be
considered in such patients."

They point out that if>the population of nondiabetic men was able to
lower its HbA1c>concentration by 0.1%, total mortality could be reduced
by 5%, and if the>concentration could be lowered by 0.2%, then total
mortality could be>reduced by 10% in this population.

And another:


Ann Intern Med 1998 Apr 1;128(7):524-33



Metabolic risk factors worsen continuously across the spectrum of nondiabetic glucose tolerance. The Framingham Offspring Study.

Meigs JB, Nathan DM, Wilson PW, Cupples LA, Singer DE
Massachusetts General Hospital, Harvard Medical School, Boston University School of Public Health, 02114, USA. jmeigs@xxxxxxxxxxxxxxxxxxx

BACKGROUND: Categorical definitions for glucose intolerance imply that risk thresholds exist, but metabolic risk for type 2 diabetes mellitus or cardiovascular disease may increase continuously as glucose intolerance increases. OBJECTIVE: To examine the distributions of the following metabolic risk factors across the spectrum of glucose tolerance: overall and central obesity, hypertension, low levels of high-density lipoprotein cholesterol, and increased triglyceride and insulin levels. DESIGN: Cross-sectional analysis. SETTING: The community-based Framingham Offspring Study. PARTICIPANTS: 2583 adults without previously diagnosed diabetes. MEASUREMENTS: Clinical data; fasting glucose, insulin, and lipid levels; and glucose and insulin levels taken 2 hours after oral challenge were collected from 1991 to 1993. Glucose tolerance was determined by 1980 World Health Organization criteria. Patients with normal glucose tolerance were categorized into quintiles of fasting glucose. The distributions of each metabolic risk factor and the metabolic sum of the six risk factors were assessed across seven categories from the lowest quintile of normal fasting glucose level through impaired glucose tolerance and previously undiagnosed diabetes. RESULTS: The mean age of patients was 54 years (range, 26 to 82 years); 52.7% of patients were women. Glucose tolerance testing found that 12.7% of patients had impaired glucose tolerance and 4.8% had previously undiagnosed diabetes. Multivariable-adjusted mean measures of risk factors and odds ratios for obesity, elevated waist-to-hip ratio, hypertension, low levels of high-density lipoprotein cholesterol, elevated triglyceride levels, and hyperinsulinemia showed continuous increases across the spectrum of nondiabetic glucose tolerance. Although a threshold effect near the upper range of nondiabetic glucose tolerance could not be ruled out for triglyceride levels in men and for insulin levels 2 hours after oral challenge in men and women, no other metabolic risk factors showed clear evidence of thresholds for increased risk. CONCLUSIONS: Metabolic risk factors for type 2 diabetes mellitus and for cardiovascular disease worsen continuously across the spectrum of glucose tolerance categories, beginning in the lowest quintiles of normal fasting glucose level.

PMID: 9518396, UI: 98175274


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the above report in MacintoshPCUNIX


--


Susan
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