MY NAME IS DAVID MURRAY,
DIRECTOR OF THE OFFICE OF
DISEASE PREVENTION.
I'M PLEASED TO WELCOME YOU ALL
TO THE 2022 ROBERT S. GORDON,
JR. LECTURE IN EPIDEMIOLOGY.
THE GORDON LECTURE IS AWARD EACH
YEAR TO A SCIENTIST WHO'S MADE
MAJOR CONTRIBUTIONS TO RESEARCH
OR TRAINING IN THE FIELD OF
EPIDEMIOLOGY OR IN THE CONDUCT
OF CLINICAL TRIALS.
THIS IS THE 27TH YEAR THAT THE
ODP HAS SPONSORED THE GORDON
LECTURE.
THE AWARD WAS ESTABLISHED IN
TRIB UNIT
TRIBUTE TO ROBERT S. GORDON AND
HIS DISTINGUISHED SERVICE TO
NIH.
OVER THE COURSE OF 30 YEARS, DRS
SENIOR LEADERSHIP POSITIONS
INCLUDING SPECIAL ASSISTANT TO
THE DIRECTOR AND CHIEF ADVISOR
FOR CLINICAL PRACTICE AND
RESEARCH.
DR. GORDON WAS AN EARLY
ORGANIZER OF EFFORTS TO ADDRESS
THE EMERGING PROBLEM OF HIV/AIDS
AND HE BECAME A KEY COORDINATOR
OF AIDS RESEARCH AT NIH.
TODAY'S SPEAKER IS DR. RENA
WELL-KNOWN ON HER RESEARCH ON
TREATMENT OF OBESITY AND ITS
APPLICATION IN TYPE 2 DIABETES.
SHE HAS PUBLISHED HUNDREDS OF
PEER REVIEWED ARTICLES ON THESE
TOPICS, CURRENTLY SHE'S THE
PRINCIPAL INVESTIGATOR ON THE
DIABETES PREVENTION PROGRAM AND
HAS DEVELOPED THE LIFESTYLE
INTERVENTION BEING USED IN ALL
THE CENTERS IN THAT STUDY.
DR. WING IS A MEMBER OF THE
COUNCIL FOR THE NATIONAL
INSTITUTE FOR DIABETES AND
DIGESTIVE AND KIDNEY DISEASES
AND SERVES ON THE NIDDK TASK
FORCE ON THE PREVENTION AND
TREATMENT OF OBESITY.
HER PRESENTATION IS ENTITLED
"SHOULD OLDER ADULTS WITH
DIABETES AND OBESITY LOSE
WEIGHT?"
PLEASE JOIN ME IN WELCOMING THE
2022 ROBERT S. GORDON JUNIOR
LECTURE AWARD RECIPIENT,
DR. REENA WING.
>>THANK YOU, DAVID.
THAT WAS A VERY NICE
INTRODUCTION.
I WANT TO THANK DR. MURRAY AND
THE OFFICE OF DISEASE PREVENTION
FOR SELECTING ME TO GIVE THIS
GORDON LECTURE IN EPIDEMIOLOGY
FOR THE YEAR 2022.
I'LL BE USING DATA FROM THE LOOK
AHEAD STUDY TO ADDRESS THE
QUESTION OF WHETHER OLDER ADULTS
WITH DIABETES AND OBESITY SHOULD
LOSE WEIGHT.
FOR THE PAST 22 YEARS, THAT'S
ALMOST A QUARTER OF A CENTURY,
I'VE HAD THE OPPORTUNITY TO BE
P.I. OF ONE OF THE SITES OF LOOK
AHEAD AND CHAIRMAN OF THE LOOK
AHEAD TRIAL.
SO YOU IT'S A GREAT PRIVILEGEO
HAVE THE CHANCE TO PRESENT TO
YOU THE RESULTS FROM THIS KEY
STUDY.
IT TAKES A VILLAGE, REALLY, TO
IMPLEMENT A STUDY SUCH AS THIS.
SO IF I WERE TO MAKE A LIST OF
ALL THE PEOPLE INVOLVED IN THE
LOOK AHEAD TRIAL, WE WOULD NEVER
GET TO ANY OF MY OTHER SLIDES.
SO WHAT I WANT TO DO IS JUST
ACKNOWLEDGE THE GROUPS OF PEOPLE
WHO HAVE BEEN INVOLVED IN THE
STUDY.
SO IT INCLUDES THE P.I., THE
COINVESTIGATORS AT EACH OF THE
16 SITES.
THE PROGRAM COORDINATORS WHO ARE
OFTEN NURSES OR INTERVENTIONISTS
AT EACH OF THE SITES WHO ARE
REALLY RESPONSIBLE FOR RUNNING
THE STUDY.
THE EXECUTIVE COMMITTEE THAT MET
ON PHONE CALLS EVERY WEEK FOR 22
YEARS.
NIH THAT WAS A PRIMARY SPONSOR
OF THIS TRIAL, AND PARTICULARLY
NIDDK, WHO PROVIDED MOST OF THE
FUNDING FOR THE STUDY.
I'VE ALSO SHOWN SOME OF THE
OTHER GROUPS THAT WERE INVOLVED
IN FUNDING THIS RESEARCH.
THE CDC AND OTHER FUNDING
AGENCIES WERE INVOLVED, AND IN
PARTICULAR, I WANT TO THANK THE
PARTICIPANTS IN THE TRIAL.
THIS STUDY COULD NOT HAVE BEEN
DONE WITHOUT THEM AND THEIR
LOYAL PARTICIPATION FOR 22
YEARS.
WHAT I WANT TO DO IS FIRST COVER
THE BACKGROUND TO LOOK AHEAD,
THEN I'LL TALK ABOUT THE DESIGN
OF THE TRIAL, THE PRIMARY
OUTCOME AND SOME OF THE POSSIBLE
EXPLANATIONS FOR THOSE RESULTS,
I'LL THEN DEAL WITH OTHER
OUTCOMES OF LOOK AHEAD AND COME
TO CONCLUSIONS AND IMPLICATIONS.
NOW WEIGHT LOSS IS RECOMMENDED
FOR OVERWEIGHT AND OBESE ADULTS.
ESPECIALLY FOR THOSE WITH TYPE .
HOWEVER, OBSERVATIONAL STUDIES
HAVE RAISED CONCERNS ABOUT THE
EFFECTS OF WEIGHT LOSS ON
MORTALITY IN OLDER ADULTS.
IN FACT, IN SOME OF THESE
STUDIES, WEIGHT LOSS NOT ONLY
DIDN'T IMPROVE MORTALITY, IT
ACTUALLY WORSENED MORTALITY.
THESE NEGATIVE EFFECTS
PERSISTED, EVEN AFTER
CONTROLLING FOR SOMETHING SUCH
AS SMOKING OR ILLNESSES SUCH AS
CANCER.
HOWEVER, OBSERVATIONAL STUDIES
CANNOT REALLY DISTINGUISH
INTENTIONAL VERSUS UNINTENTIONAL
WEIGHT LOSS.
THE BEST WAY TO DO THAT IS
THROUGH A CLINICAL TRIAL IN
WHICH SOME PEOPLE ARE RANDOMLY
ASSIGNED TO LOSE WEIGHT
INTENTIONALLY, AND THE OTHERS
ARE FOLLOWED IN A CONTROL GROUP
OR IN SOME OTHER GROUP OVER
TIME.
NOW PRIOR TO DOING LOOK AHEAD,
THERE HAD BEEN ALSO MANY SMALL
SHORT TERM CLINICAL TRIALS,
WHICH SUGGESTED THAT INTENTIONAL
WEIGHT LOSS HAS POSITIVE EFFECTS
ON GLYCEMIC CONTROL AND CVD RISK
FACTORS.
THERE WAS A META ANALYSES OF
THESE SMALL STUDIES THAT RAISED
A SUGGESTION THERE MIGHT BE A
POSITIVE EFFECT ON MORTALITY AS
WELL.
IT WAS CLEAR, THOUGH, THAT
ANSWERING THE QUESTION WOULD
REQUIRE A LARGE, LONG-TERM
RANDOMIZED TRIAL OF INTENTIONAL
WEIGHT LOSS IN OLDER ADULTS.
BASED ON THE STRONG INCIDENCE OF
OBESITY AND DIABETES, AND
CONCERNS REGARDING THE BENEFITS
OF WEIGHT LOSS, NIH DECIDED THAT
A CLINICAL TRIAL WAS NEEDED ON
THIS TOPIC AND THAT IT SHOULD BE
DONE IN TYPE 2 DIABETICS WITH
OVERWEIGHT AND OBESITY.
NOW I DON'T WANT YOU TO HAVE THE
FEELING THAT LOOK AHEAD JUST
SUDDENLY CAME TO PASS.
IT ACTUALLY STARTED IN THE YEAR
1999 OR 2000, BUT THE FOUNDATION
FOR THE TRIAL HAD BEEN LAID MANY
YEARS BEFORE.
IN THE 1980s AND 90s, THERE
HAD BEEN MANY SMALL TRIALS
TESTING COMPONENTS OF INTENSIVE
LIFESTYLE INTERVENTION.
FOR EXAMPLE, COMPARING DIET
VERSUS DIET PLUS EXERCISE, OR
JUST STUDIES SHOWING THE
BENEFITS OF INCLUDING MEAL
REPLACEMENT PRODUCTS AS PART OF
THE DIETARY PRESCRIPTION.
THE DIABETES PREVENTION PROGRAM,
ANOTHER LARGE RANDOMIZED TRIAL
FUNDED BY NIDDK, WAS CRITICAL IN
PAVING THE WAY FOR LOOK AHEAD.
THIS STUDY SHOWED THAT LIFESTYLE
INTERVENTIONS CAN BE
STANDARDIZED AND PRODUCE WEIGHT
LOSS IN DIVERSE POPULATIONS,
INCLUDING IN MINORITY GROUPS.
AND PERHAPS MOST IMPORTANTLY,
THE MODEST WEIGHT LOSSES CAN
PRODUCE CLINICALLY SIGNIFICANT
CHANGES IN HEALTH.
I'D LIKE TO ILLUSTRATE THAT WITH
A FEW SLIDES FROM THE DIABETES
PREVENTION PROGRAM.
THE DIABETES PREVENTION PROGRAM
INVOLVED 3,000 INDIVIDUALS WITH
PREDIABETES, SO AT HIGH RISK FOR
DEVELOPING DIABETES.
THESE INDIVIDUALS WERE RANDOMLY
ASSIGNED TO LIFESTYLE,
METFORMIN, WHICH IS A DRUG
THAT'S USED TO TREAT DIABETES,
OR TO PLACEBO.
I WAS THE PI OF THE LIFESTYLE
RESOURCE CORE.
WE DESIGNED THE INTERVENTION,
TRAIN THE INTERVENTIONISTS AND
ENSURE FIDELITY OF THE
INTERVENTION ACROSS THE SITES.
I BELIEVE THE LIFESTYLE
INTERVENTION GOALS WERE MODEST.
THE GOAL WAS FOR EACH PERSON TO
LOSE 7% OF THEIR BODY WEIGHT,
WHICH FOR SOMEBODY STARTING OUT
THE STUDY AT 200 POUNDS WAS JUST
ABOUT A 7-KILOGRAM OR 14-POUND
WEIGHT LOSS.
THE CALORIE GOAL TO ACHIEVE THAT
WAS PUT AT 1200 TO 1800 CALORIES
A DAY WITH LESS THAN 25% FAT AND
PARTICIPANTS WERE GRADUALLY
ENCOURAGED TO INCREASE THEIR
EXERCISE UNTIL THEY WERE DOING
175 MINUTES PER WEEK OF BRISK
ACTIVITY.
THIS SLIDE SHOWS THE WEIGHT
CHANGES THAT WERE ACHIEVED IN
THE DIABETES PREVENTION PROGRAM.
AS YOU CAN SEE, IT'S SIX MONTHS
PARTICIPANTS HAD LOST ABOUT
7 KILOGRAMS OR 7% OF THEIR BODY
WEIGHT, SO RIGHT ON TARGET.
THEY MAINTAIN THAT AT ONE YEAR
AND THEN GRADUALLY REGAIN SOME
WEIGHT OVER TIME.
HOWEVER, THROUGHOUT THE FOUR
YEARS, THEIR WEIGHT CHANGES IN
THE LIFESTYLE ARM WERE
SIGNIFICANTLY BETTER THAN THOSE
IN PLACEBO.
HOWEVER AS I EMPHASIZE BEFORE,
THESE WEIGHT LOSSES I BELIEVE
ARE QUITE MODEST AND YET THEY
HAD A VERY ROBUST EFFECT ON THE
INCIDENCE OF DIABETES.
SO AT THE VERY BEGINNING OF THE
TRIAL SHOWN ON THE LEFT OF THE
SIDE, YOU CAN SEE NOBODY HAD
DIABETES BECAUSE THEY WERE ALL
AT RISK FOR DEVELOPING IT BUT
NONE OF THEM HAD IT YET.
EACH SIX MONTHS, AN ORAL GLUCOSE
TOLERANCE TEST WAS CONDUCTED TO
SEE WHO HAD CONVERTED TO HAVE
DIABETES.
YOU CAN SEE BY THE END OF THE
FOUR YEARS, ABOUT 40% OF THE
PLACEBO PARTICIPANTS HAD
DEVELOPED DIABETES.
COMPARED TO ABOUT 30% IN
METFORMIN, OR 20% IN LIFESTYLE
INTERVENTION.
SO INTENSIVE LIFESTYLE
INTERVENTION REDUCED THE RISK OF
DEVELOPING DIABETES BY 58%.
AND WAS NEARLY TWICE AS
EFFECTIVE AS THE DRUG METFORMIN.
SO I BELIEVE THAT DPP REALLY
HELPED US ESTABLISH THAT WE CAN
PRODUCE WEIGHT LOSS IN A LARGE
TRIAL SUCH AS THIS AND EVEN A
MODEST WEIGHT LOSS OF 14 POUNDS
CAN HAVE A LARGE IMPACT ON
HEALTH.
I BELIEVE THAT'S WHAT LED NIH TO
BE CONFIDENT THAT THEY COULD
LAUNCH THE LOOK AHEAD TRIAL.
IN WHICH WE WERE TRYING TO ASK
THE QUESTION OF WHETHER
LIFESTYLE INTERVENTION COULD
REDUCE THE RISK EVER
CARDIOVASCULAR MORBIDITY AND
MORTALITY AND IN THOSE WHO ALY
HAD TYPE 2 DIABETES.
WE STARTED RECRUITMENT IN 2000
AND RECRUITED GRADUALLY OVER THE
NEXT COUPLE OF YEARS.
ALL WERE RANDOMLY ASSIGNED TO
EITHER INTENSIVE LIFESTYLE
INTERVENTION WHICH I'LL DESCRIBE
IN A MOMENT OR TO DIABETES
SUPPORT AND EDUCATION, WHICH WAS
THE CONTROL OR COMPARISON
CONDITION.
THE PRIMARY OUTCOME WAS A
COMPOSITE MEASURE OF
CARDIOVASCULAR MORBIDITY AND
MORTALITY.
NOW THE FIVE THOWN 145
PARTICIPANTS WHO ENTERED THIS
TRIAL CAME FROM 16 DIFFERENT
CLINICAL SITES THROUGHOUT THE
UNITED STATES.
THEY ALL HAD TYPE 2 DIABETES,
OVERWEIGHT AND OBESITY.
THEY WERE AGE 45 TO 76 WITH A
MEAN OF 59 YEARS.
37% WERE FROM MINORITY
ETHNIC/RACIAL GROUPS.
THAT WAS VERY IMPORTANT TO US
BECAUSE DIABETES
DISPROPORTIONATELY AFFECTS
MINORITY GROUPS SO WE WANTED OUR
STUDY TO HAVE POPULATION --
SIMILAR TO THE POPULATION
AFFECTED BY DIABETES.
IN ADDITION, THEY HAD TO PASS A
MAXIMUM CVD STRESS TEST.
THESE PARTICIPANTS WERE RANDOMLY
ASSIGNED TO DIABETES SUPPORT AND
EDUCATION WHICH WA THE CONTROL
GROUP OR INTENSIVE LIFESTYLE
INTERVENTION.
THE CONTROL GROUP ATTENDED THREE
TO FOUR EDUCATIONAL SESSIONS PER
YEAR RELATED TO DIET, EXERCISE,
OR SOCIAL SUPPORT.
THE INTERVENTION DWREUP WAS
REALLY A VERY INTENSIVE
INTERVENTION.
THEY RECEIVED WEEKLY COUNSELING
FOR THE FIRST YEAR, AND THEY HAD
A GOAL OF LOSING 10% OF THEIR
WEIGHT.
A SOMEWHAT HIRE GOAL WE HAD IN
DPP.
THEY WERE ABLE TO ACCOMPLISH
THAT BY EATING A LOWER CALORIE
DIET AND THEY USED MEAL
REPLACEMENT PRODUCTS WHICH AS I
SAID HAD BEEN SHOWN TO IMPROVE
WEIGHT LOSSES.
AND THEY GRADUALLY WERE
ENCOURAGED TO INCREASE THEIR
EXERCISE TO 175 MINUTES PER WEEK
OF PHYSICAL ACTIVITY.
AS IN DPP IN LOOK AHEAD, THE
INTERVENTION WAS STRONGLY
BEHAVIORAL, INCLUDING STRATEGIES
SUCH AS GOAL SETTING AND
SELF-MONITORING.
IN YEARS TWO TO FOUR, WE REDUCE
THE AMOUNT OF CONTACT BUT THEY
STILL HAD MONTHLY CONTACT AND IN
YEARS FIVE ON, WE KEPT IT AT
QUARTERLY CONTACT.
BUT THROUGHOUT YEARS TWO TO THE
END OF THE STUDY, THEY HAD
REFRESHER SESSIONS AS NEEDED TO
ENCOURAGE THEM TO STAY ON TRACK
WITH THEIR DIET AND EXERCISE.
THE INTERVENTION CONTINUED
THROUGH THE YEAR 2012 SO THAT
MEANS FOR NINE TO 11 YEARS, EACH
PARTICIPANT WAS RECEIVING
INTERVENTION.
OF IN DESIGNING THE STUDY, WE
MADE SERL DESIGN DECISIONS WHICH
ARE IMPORTANT FOR YOU TO THINK
ABOUT IN TERMS OF THE OUTCOMES
WE ACHIEVED.
ONE DECISION WE MADE WAS TO
ENRICH THE SAMPLE WITH
PARTICIPANTS WITH CVD HISTORY IN
ORDER TO INCREASE THE POWER OF
THE STUDY.
THIS IS TYPICALLY DONE IN CBD
STUDIES SO 14% OF OUR
PARTICIPANTS HAD A CBD HISTORY.
WE ALSO DECIDED AHEAD THAT
PARTICIPANTS AND THEIR
PHYSICIANS WERE TO BE GIVEN
FEEDBACK ON THEIR ANNUAL BLOOD
WORK.
AND THAT THEIR MEDICATION
ADJUSTMENTS WERE TO BE MADE BY
THEIR OWN PHYSICIANS, NOT BY THE
STUDY TRIAL.
AND WE ALSO DECIDED AHEAD THAT
ILI WOULD DECREASE IN INTENSITY
OVER TIME AS I JUST SHOWED YOU.
THE GOAL OF ILI WAS TO LOSE
WEIGHT AS I SAID, 10% WEIGHT
LOSS, AND TO INCREASE PHYSICAL
ACTIVITY.
THIS SLIDE SHOWS WE ACHIEVED OUR
WEIGHT LOSS GOALS.
INITIALLY, THE WEIGHT LOSS WAS
8.5% AT YEAR ONE.
NOT QUITE THE 10% BUT CLEARLY AN
EXCELLENT WEIGHT LOSS AND EVEN
GREATER THAN WE ACHIEVED IN DPP.
OVER TIME, THERE WAS SOME
REGAIN, BUT AS YOU CAN SEE HERE,
ILI, WHICH IS SHOWN IN BLUE, HAD
BETTER WEIGHT LOSSES THAN DSE
SHOWN IN RED THROUGHOUT THE
ENTIRE TRIAL.
BY THE WAY, I'LL KEEP THAT COLOR
SCHEME THROUGHOUT ALL MY SLIDES
SO THAT HOPEFULLY YOU'LL BE ABLE
TO FOLLOW THEM OVER TIME.
SO THE NEXT SLIDE SHOWS THE
CHANGES IN CARDIOVASCULAR
FITNESS WHICH ACHIEVED WITH
SUBMAXIMAL TESTS.
THESE WERE CONDUCTED AT YEARS
ONE, TWO AND FOUR, AND AS YOU
CAN SEE HERE, THEIR FITNESS
GREATLY IMPROVED IN ILI MUCH
MORE SO THAN IN DSE.
AGAIN, THOUGH, THE GREATEST
INCREASE WAS AT YEAR ONE AND
GRADUALLY DECREASED OVER TIME.
ALTHOUGH WE DID NOT ASSESS
FITNESS BEYOND YEAR 4, WE DID
FIND PHYSICAL FUNCTION MEASURES
SUCH AS GAIT SPEED REMAINED
FASTER IN ILI THROUGHOUT THE
TRIAL.
THIS NEXT SLIDE SHOWS YOU THE
IMPROVEMENTS IN HEMOGLOBIN A1C.
AND AGAIN, THEY REALLY PARALLEL
THE WEIGHT LOSSES I SHOWED YOU A
MINUTE AGO, WHERE AGAIN, ILI HAS
VERY BIG IMPROVEMENT INITIALLY,
LESS OVER TIME BUT REMAINS
SIGNIFICANTLY DIFFERENT THAN DSE
THROUGHOUT.
NOW, HAVING ACHIEVED OUR WEIGHT
LOSSES AND OUR HEMOGLOBIN A1C
IMPROVEMENTS AND OUR FITNESS
CHANGES, WE EXPECTED OR HOPED
THAT OUR CUMULATIVE HAZARD RATIO
FOR OUR PRIMARY OUTCOME WOULD BE
DIFFERENT THAN ILI MIGHT HAVE A
LOWER INCIDENCE OF PROBLEMS THAN
DSE.
HOWEVER, THE CUMULATIVE
INCIDENCE FOR FATAL AND
NON-FATAL MI AND STROKES OR
HOSPITALIZED ANGINA WHICH WAS
OUR PRIMARY OUTCOME SHOW NO
DIFFERENCES AS SEEN HERE.
I CAN'T IMAGINE TWO MORE
PARALLEL LINES, MORE SIMILAR
LINES FOR D DSE AND ILI OVER TE
10 YEARS.
THE SAME WAS TRUE FOR ALL OF THE
SECONDARY CVD COMPOSITE
OUTCOMES.
TO SUM, THIS WAS A SURPRISING OR
DISAPPOINTING FINDING.
LEADING TO SEVERAL DIFFERENT
EXPLANATIONS FOR THESE RESULTS.
PROBABLY THE CENTRAL MOST
APPROPRIATE INTERPRETATION IS
THAT WEIGHT LOSS DOES NOT AFFECT
CVD RISK IN OVERWEIGHT ADULTS
WITH DIABETES.
HOWEVER, OTHERS HAVE SOUGHT
OTHER EXPLANATIONS.
FOR EXAMPLE, SOMEONE SAID THE
SAMPLE WAS TOO SICK.
THEY HAD CVD.
OTHERS HAVE SAID THE SAMPLE WAS
TOO HEALTHY BECAUSE THEY HAD TO
PASS A TREADMILL TEST.
OTHERS HAVE SAID WELL, THERE WAS
BETTER RISK FACTOR MANAGEMENT
OVER TIME, AND THAT MAY HAVE
OBSCURED THE EFFECTIVE HE WAS
LOSS.
WEIGHT
LOSS.
ANOTHER POSSIBILITY IS THAT THE
WEIGHT LOSSES WERE NOT LARGE
ENOUGH, OR THAT THOSE WHO DID
NOT LOSE WEIGHT MAY HAVE BLUNTED
ANY POSITIVE EFFECTS OF WEIGHT
LOSS.
SOME HAVE QUESTIONED WHETHER THE
WEIGHT LOSS IS ES ACHIEVED BY I
CAN BE SUFFICIENT.
THEY POINT TO THE FACT THAT FROM
BARIATRIC SURGERY WHERE WEIGHT
LOSSES ARE MUCH BIGGER, THEY
HAVE BEEN ABLE TO SHOW THAT
THERE WERE DECREASES IN THE CVD
INCIDENCE.
SO IN LOOK AHEAD, WE CANNOT TEST
ANY OF THESE HYPOTHESES OR THESE
POSSIBILITY EXPLANATIONS.
BUT WE CAN LOOK AT POST HOCK
DATA ANALYSIS THAT MIGHT GIVE US
SOME GLIMPSE OF WHAT MIGHT HAVE
BEEN HAPPENING IN OUR TRIAL.
BUT KEEP IN MIND WE CAN'T
RANDOMIZE PEOPLE TO EITHER HAVE
A LARGER WEIGHT LOSS OR NOT AS
LARGE A WEIGHT LOSS.
SO LET'S LOOK AT EACH OF THESE
PROPOSED EXPLANATIONS FOR A
MINUTE.
ONE THAT I'M GOING TO FOCUS ON
WAS THAT THE SAMPLE MIGHT HAVE
BEEN TOO SICK.
NOW IN TERMS OF THIS HYPOTHESIS,
IT'S VERY INTERESTING TO DIVIDE
THE GROUPS INTO THOSE WITH A CVD
HISTORY AND THOSE WITHOUT AT
BASELINE.
SO IF YOU LOOK AT THE GROUP
WITHOUT A CVD HISTORY, IT
INCLUDES -- THIS IS THE GROUP
WITHOUT A CVD HISTORY.
AND THAT INCLUDED 86% OF OUR
SAMPLE HAD NO CVD HISTORY.
AND YOU CAN SEE THERE THAT THERE
WAS A SLIGHTLY BUT
NON-SIGNIFICANTLY LOWER RISK OF
THE PRIMARY OUTCOME IN ILI THAN
IN DSE IN THOSE WITH NO
CARDIOVASCULAR DISEASE HISTORY.
ODDS RATIO OF .86.
BUT IT WAS A NON-SIGNIFICANT
EFFECT.
OVER HERE IN THE CVD HISTORY
GROUP, THERE WAS ALSO A
NON-SIGNIFICANT EFFECT WITH S
IN THE OPPOSITE DIRECTION.
1.13 HAS A RATIO.
LEADING TO A NON-SIGNIFICANT
INTERACTION BUT VERY CLOSE TO
SIGNIFICANT.
YOU CAN ALSO SEE THE EXPECTATION
THAT PEOPLE WITH CVD HISTORY
WOULD HAVE GREATER RISK OF HEART
DISEASE OUTCOMES -- EXCUSE ME --
THAT THOSE WITH THE HISTORY
WOULD HAVE A GREATER RISK THAN
THOSE WITHOUT A HISTORY AND SURE
ENOUGH, WE FOUND THAT.
BUT IT DOES SUGGEST TO US THAT
IF WE HAVE DONE OUR INTERVENTION
WITH PEOPLE WHO DID NOT HAVE CVD
AT THE BEGINNING, WE MIGHT HAVE
ACHIEVED A DIFFERENT EFFECT.
NOW MORE RECENTLY, THERE'S BEEN
ANOTHER STUDY OF OURS, A POST
HOC EXPLANATION, THAT ALSO
SUGGESTS A SIGNIFICANT BENEFIT
ON CVD INCIDENCE IN THOSE WHO
ARE HEALTHIEST.
HERE INSTEAD OF USING CVD
HISTORY, WE USED THE DEFICIT
ACCUMULATION MODEL TO LOOK AT
THE TOTAL NUMBER OF HEALTH
DEFICITS A PERSON HAD AT
BASELINE.
WE DIVIDED PEOPLE INTO THREE
DIFFERENT TERTILES ACCORDING TO
PROBLEMS THEY HAD AT BASELINE.
WE USED THE MIDDLE TERTILE AS
OUR REFERENCE GROUP.
AND AS YOU CAN SEE HERE, THOSE
PEOPLE IN THE LOWEST SOMEBODY
TERTILE WITH THE FEWEST PROBLEMS
AT BASELINE ACTUALLY SHOWED A
SIGNIFICANT REDUCTION IN THE
HAZARD RATIO FOR THE PRIMARY CVD
OUTCOME.
IN CONTRAST, THERE WAS A
NON-SIGNIFICANT WORSENING IN
THEIR OUTCOMES, SO AGAIN, I'LL
SUGGEST THAT PERHAPS INTERVENING
EARLIER IS GOING TO BE HELPFUL.
THIS IS A POINT I'LL KEEP MAKING
THROUGHOUT THE TRIAL, THROUGHOUT
MY SLIDES TODAY.
SO ANOTHER PROPOSED EXPLANATION
IS IMPROVING THE RISK FACTOR
MANAGEMENT IMPROVED HEALTH OF
THE CONTROL CONDITION.
ILI IN BLUE, AS YOU CAN SEE
EVERY SLIDE AT EVERY TIME POINT,
THERE IS GREATER USE OF
ANTIHYPERTENSIVES, STATINS, AND
INSULIN IN THE CONTROL GROUP
THAN THERE WAS IN THE
INTERVENTION GROUP.
THIS SLIDE ALSO SHOWS MEDICAL
CARE WAS CHANGING DRAMATICALLY
OVER THE COURSE OF THE STUDY,
LIKELY REDUCING CVD EVENTS AND
STATISTICAL POWER AND ALSO
AFFECTING RESULTS.
YOU CAN SEE ANTIHYPERTENSIVE USE
GOING UP, STATINS GOING UP A
LOT, INSULIN USE GOING UP A LOT.
THE HIGHER USE OF STATINS IN DSE
LED TO LOWER LEVELS OF LDL IN
DSE THAN IN ILI, AS SHOWN HERE.
SO PERHAPS ONE EXPLANATION FOR
OUR RESULTS IS THAT WE HAD TWO
DIFFERENT MECHANISMS OPERATING
FOR THE TWO DIFFERENT ARMS.
IN ILI, PERHAPS IT WAS WEIGHT
LOSS.
IN THE LIFESTYLE INTERVENTION,
IT WAS IMPROVING OUR RISK OF
HEART DISEASE.
BULL IN BUT IN DSE, IT MIGHTN
THE LOWER LDL LEVELS LEADING TO
IMPROVEMENTS.
SO ANOTHER EXPLANATION WE
PROPOSED WAS THAT THE WEIGHT
LOSSES WERE NOT LARGE ENOUGH, OR
THAT THOSE WHO DID NOT LOSE
WEIGHT BLUNTED THE EFFECT OF
WEIGHT LOSS.
TO ADDRESS THIS HYPOTHESIS, WE
CONDUCTED A SECONDARY ANALYSIS
AND WE SHOWED THE RESULTS THAT
I'M GOING TO TALK ABOUT HERE.
USING EITHER THE DIABETES
SUPPORT AND EDUCATION GROUP AS A
WHOLE, ORTHOS IN ILI WHO GAINED
WEIGHT OR REMAINED WEIGHT STABLE
AS I'VE SHOWN HERE.
WE FOUND A SIGNIFICANT REDUCTION
IN THE PRIMARY OUTCOME, BUT ONLY
FOR THOSE INDIVIDUALS WHO LOST
10% OR MORE OF THEIR BODY
WEIGHT.
THE RIGHT-HAND BAR.
THIS GROUP HAD A SIGNIFICANT
REDUCTION IN THEIR RISK OF
PRIMARY OUTCOME RELATIVE TO HERE
THE GAINERS OR THE STABLE.
THIS ANALYSIS IS INTERESTING AND
IT SUGGESTS THAT LARGER WEIGHT
LOSSES MAY HAVE BEEN NEEDED TO
PRODUCE A GREATER EFFECT.
OR THAT WE NEEDED A GREATER
NUMBER OF PARTICIPANTS LOSING
10%.
BUT THIS IS A POST HOC ANALYSIS.
NOT A RANDOMIZED COMPARISON.
SO ALTHOUGH WE INCLUDED
COVARIATES IN OUR ANALYSES,
THOSE INDIVIDUALS WHO LOST MORE
WEIGHT SHOWN IN THE RIGHT BAR
MAY HAVE DIFFERED FROM THOSE WHO
WERE GAINING OR WEIGHT STABLE IN
MANY DIFFERENT WAYS THAT WE
COULDN'T KNOW ABOUT OR DIDN'T
CONTROL FOR.
DUE TO THE LACK OF SIGNIFICANT
DIFFERENCES IN THE PRIMARY
OUTCOME AND OF FUTILITY
ANALYSIS, NIH DECIDED TO STOP
ALL OF THE INTERVENTIONS IN THE
YEAR 2012.
BUT CONTINUED LOOK AHEAD AS AN
OBSERVATIONAL STUDY.
THIS PROVIDED US WITH A
WONDERFUL OPPORTUNITY TO EXAMINE
THE EFFECT OF THE FIRST 10 YEARS
OF INTERVENTION ON OTHER HEALTH
OUTCOMES RELATED TO DIABETES AND
OBESITY.
IT ALSO PROVIDED AN OPPORTUNITY
FOR US TO ADD NEW MEASURES
RELEVANT TO AGING.
THE LOOK AHEAD TRIAL IS STILL
ONGOING.
IT'S NOW FUNDED BY NIA, AND IT'S
BEING DONE ENTIRELY BY PHONE
CONTACT WITH OUR PARTICIPANTS.
BUT I DID WANT TO ADVISE YOU OR
LET YOU KNOW THAT IT IS ONGOING.
NOW ALTHOUGH THE PRIMARY OUTCOME
OF CBD WAS NOT SIGNIFICANT,
INTENSIVE LIFESTYLE INTERVENTION
WAS FOUND TO HAVE MANY POSITIVE
EFFECTS ON MANY OTHER OUTCOMES.
SIEF SELECTED I'VE SELECTS
LIST YEAR AND I'M EVEN GOING TO
PICK A SMALLER NUMBER OF THOSE
TO TALK ABOUT IN THESE NEXT FEW
SLIDES.
SO ONE THING THAT HAS BEEN SHOWN
IS THERE WAS AN ASSOCIATION
BETWEEN BEING IN INTENSIVE
LIFESTYLE INTERVENTION AND THE
POSSIBILITY OF REMISSION OF TYPE
2 DIABETES.
NOW REMISSION WAS DEFINED AS NOT
NEEDING DIABETES MEDICATIONS AND
STILL HAVING NORMAL GLUCOSE OR
GLUCOSE LEVELS IN A NON-DIABETIC
RANGE.
ILI HAD GREATER PREVALENCE OF
REMISSION IN YEARS 1, 2, 3 AND .
THE GREATEST BENEFITS WERE IN
YEAR ONE, AND ALSO THE GREATEST
BENEFITS WERE IN THOSE WHO WERE
HEALTHIEST AT BASELINE.
ANOTHER POSITIVE EFFECT WAS ON
THE INCIDENCE OF NEPHROPATHY.
SO ONE OF THE MICROVASCULAR
COMPLICATIONS OF DIABETES WAS
ALSO MARKETEDLY MARKEDLY R
LIFESTYLE INTERVENTION.
AS SEEN HERE, THE CONTROL GROUP
IN BLUE HAS A MUCH HIGHER RISK
OF DEVELOPING THIS HIGH RISK
CHRONIC KIDNEY DISEASE RELATIVE
TO OUR INTENSIVE LIFESTYLE
INTERVENTION.
I THINK THIS IS ONE OF THE OTHER
INTERESTING FINDINGS OF LOOK
AHEAD.
BECAUSE IT DEALS REALLY WITH
TREATMENT, NOT JUST PREVENTION
OF SOMETHING.
BUT IT DEALS WITH TREATMENT OF
AN ONGOING PROBLEM, IN THIS
CASE, SLEEP APNEA.
IN THIS SUBGROUP OF 264 ADULTS
WITH TYPE 2 DIABETES AND
PREVIOUSLY DIAGNOSED OBSTRUCTIVE
SLEEP APNEA, WE FOUND AN
INTENSIVE LIFESTYLE INTERVENTION
REDUCED THE INCIDENCE OF OSA,
AND IT WAS FAR GREATER REDUCTION
IN THE INTERVENTION GROUP THAN
IN THE CONTROL GROUP.
THIS SLIDE SHOWS YOU THE
INCIDENCE -- THE REDUCTION,
EXCUSE ME, IN OBSTRUCTIVE SLEEP
APNEA IN THESE PATIENTS AT YEAR
FOUR, AND YOU CAN SEE HERE THE
MARKED NUMBER OF PEOPLE WITH
IMPROVED OSA IN ILI VERSUS DSE.
IF YOU ACTUALLY LOOK AT
REMISSION RATES AT FOUR YEARS,
ILI HAD 20.7% OF THEIR
PARTICIPANTS NO LONGER HAD
OBSTRUCTIVE SLEEP APNEA COMPARED
TO ONLY 4% IN THE CONTROL GROUP.
NOW I'D LIKE TO JUST LOOK AT ONE
OF THE PUBLIC HEALTH KIND OF
OUTCOMES, SO I HOPE I'VE COVERED
SOME PREVENTION AND TREATMENT
OUTCOMES, NOW I JUST WANTED TO
LOOK AT ONE PUBLIC HEALTH ONE,
WHICH IS THAT ILI HELPED REDUCE
HEALTHCARE COSTS.
IT WAS A 15% REA DUCKS IN E
NURM BER OF DAYS IN THE
HOSPITAL, 5% REDUCTION IN
MEDICATION COST, LEAVING TO A
SAVINGS OF $5,280 PER PERSON
OVER THE 10 YEARS.
HOWEVER, THE COST OF OFFERING
ILI EXCEEDED THAT OF THE COST OF
DSE.
SO ILI COST $1,500 PER
PARTICIPANT PER YEAR VERSUS ONLY
$122 PER PARTICIPANT PER YEAR
FOR DSE WHEN AVERAGED OVER THE
10 YEARS.
IN TERMS OF COST-EFFECTIVENESS,
OUR OUTCOME IS REALLY DEPENDENT
ON WHICH MEASURE OF HEALTH
UTILITIES WE UTILIZED.
NOW I DON'T WANT YOU TO HAVE THE
IDEA THAT EVERYTHING WAS
POSITIVE FROM ILI, ALTHOUGH I
WOULD ARGUE THAT MOST OF THEM
WERE, BUT THERE WERE SOME
NEGATIVE EFFECTS OF ILI ON
HEALTH, PARTICULARLY IN TERMS OF
LOSS OF LEAN BODY MASS, AND AN
INCREASED RISK OF FRACTURES.
WE COMPLETED DEXA MEASURES ON A
SUBSET OF PARTICIPANTS AT
BASELINE YEARS 1, 4, 8 AND AT
THE END OF THE TRIAL.
AS PARTICIPANTS LOST WEIGHT AT
YEAR ONE, THEY HAD MARKED
IMPROVEMENTS IN BOTH THEIR FAT
MASS AND THEIR LEAN MASS.
HERE, BY THE WAY, THE DSE GROUP
IS SHOWN IN THE SOLID LINE AND
THE ILI IN THE DOTTED LINE.
BUT AS ILI GRADUALLY REGAINED
WEIGHT BETWEEN YEARS 1 AND 4 OR
YEARS 1 AND 8 EVEN, YOU CAN SEE
THAT THEIR FAT MASS INCREASED
BUT THEIR LEAN MASS DID NOT
INCREASE.
WE'RE NOT SURE WHAT THE HEALTH
CONSEQUENCES OF THIS WILL BE,
BUT ONE POSSIBILITY IS THAT IT
WOULD INCREASE THE RISK OF
FRACTURES IN ILI RELATIVE TO
DSE.
THERE WERE NO DIFFERENCES IN THE
INCIDENCE OF TOTAL FRACTURES.
HOWEVER, AS SHOWN HERE, THERE
WERE DIFFERENCES IN THE
CUMULATIVE INCIDENCE OF FRAILTY
FRACTURES, WHICH ARE FRACTURES
OF THE HIP, PELVIS, UPPER ARM OR
SHOULDER.
THESE WERE GREATER IN FEMALES
THAN IN MALES, AND WITHIN EACH
GENDER WERE GREATER IN THE
INTERVENTION GROUP THAN IN THE
CONTROL GROUP.
SO THIS IS A CONCERN TO US
BECAUSE OBVIOUSLY YOU DO NOT
WANT TO HAVE PEOPLE HAVING
FRAILTY FRACTURES, AND THIS MAY
HAVE BEEN RELATED TO THEIR LOSS
OF LEAN MASS.
NOW, I ALSO WANT TO EMPHASIZE
THE FACT THAT THERE WERE NO
SIGNIFICANT EFFECTS OF ILI ON
HEALTH FOR SEVERAL VERY KEY
HEALTH PROBLEMS.
I'VE ALREADY POINTED OUT THAT
FOR OUR PRIMARY OUT COME OF CVD,
THERE WERE NO EFFECTS.
I ALSO WANT TO TELL YOU THAT
THERE WERE NO EFFECTS FOR
CANCER, COGNITIVE FUNCTION, OR
COGNITIVE IMPAIRMENT DEMENTIA.
I'LL SHOW YOU SOME EXAMPLES OF
THIS ON THE NEXT SLIDES.
THIS SLIDE LOOKS AT THE RISK OF
CANCER, AND YOU CAN SEE HERE
NONE OF THE P VALUES ARE
SIGNIFICANT.
NO DIFFERENCES STATISTICALLY
SIGNIFICANT DIFFERENCES BETWEEN
DSE AND ILI FOR CANCER RISK.
THERE'S A TREND FOR A POSITIVE
EFFECT IN OBESITY-RELATED
CANCERS BUT IT'S JUST A P OF
.10.
NO DIFFERENCES AGAIN IN CANCER
MORTALITY.
WE ALSO HAD NO EFFECTS ON
COGNITIVE FUNCTION, BUT WE DID
HAVE POSITIVE EFFECTS ON BRAIN
STRUCTURE WITH POSITIVE BENEFITS
IN ILI VERSUS DSE.
HOWEVER WE HAVE NOT FOUND ANY
EFFECTS THUS FAR ON COGNITIVE
IMPAIRMENT.
MILD COGNITIVE IMPAIRMENT OR
DEMENTIA.
THIS MAY BE BECAUSE OUR RATES OF
BOTH OF THESE PROBLEMS HAS BEEN
SO LOW THUS FAR.
SO OUR ADJUDICATED MCI WAS ONLY
6.4% IN BOTH ILI AND DSE AND
ADJUDICATED DEMENTIA WAS ONLY
1.8% IN BOTH.
SO THAT'S ONE OF THE REASONS
WE'LL BE ABLE TO CONTINUE WITH
FUNDING TO LOOK AT THESE
COGNITIVE IMPAIRMENTS OVER TIME.
AGAIN THOUGH THERE WERE
SIGNIFICANT INTERACTIONS BETWEEN
BASELINE BMI AND CVD HISTORY.
NOW MOST RECENTLY, WE HAVE ADDED
ANOTHER NON-SIGNIFICANT EFFECT
OF ILI ON HEALTH.
IT'S IN TERMS OF OVERALL
MORTALITY.
WITH ADJUDICATED MORTALITY AND
ITS CAUSES OVER THE ENTIRE
STUDY, AND WE'VE JUST PUBLISHED
THESE RESULTS IN A VERY RECENT
ISSUE OF DIABETES CARE.
THIS SLIDE SHOWS THE TOTAL
MORTALITY OVER THE ENTIRE STUDY.
DURING THE INTERVENTION, THE
TRANSITION, AND THE POST
INTERVENTION PHASES.
OVER THIS ENTIRE PERIOD, THE
HAZARD RATIO WAS .92.
SO THERE WAS AN 8% REDUCTION IN
ALL CAUSE MORTALITY FOR ILI
VERSUS DSE, BUT THIS WAS NOT
SIGNIFICANT, A P OF .16.
SO ILI NEITHER IMPROVED NOR
WORSENED ALL CAUSE MORTALITY
RELATIVE TO DSE.
HERE I'VE SHOWN YOU THE THE
ADJUDICATED PRIMARY CAUSES OF
DEATH.
THERE WERE NO DIFFERENCES IN
CANCER RISK, CVD OR OTHER.
HOWEVER, ONE OF THE THINGS I
THINK THAT'S INTERESTING IN THIS
SLIDE IS THAT CANCER AND OTHER
ARE HIGHER ADJUDICATED PRIMARY
CAUSES OF DEATH IN THIS
POPULATION.
AGAIN, WE'VE CONDUCTED A POST
HOC ANALYSIS COMPARING ALL CAUSE
MORTALITY IN ILI ACCORDING TO
THE MAGNITUDE OF THEIR WEIGHT
LOSSES, COMPARED TO DSE AS A
WHOLE.
WE SHOW THAT THOSE INDIVIDUALS
WHO HAD THE BIGGEST WEIGHT
LOSSES AT ONE YEAR, SO THAT'S A
WEIGHT LOSS OF 10% OR MORE, HAD
LESS MORTALITY OVER THE
SUBSEQUENT PERIOD OF THE STUDY.
SO BETWEEN YEARS TWO AND THE END
OF THE TRIAL IN ILI VERSUS DSE.
IN CONTRAST, THOSE INDIVIDUALS
WHO HAD THE LEAST WEIGHT LOSS OR
ACTUALLY GAINED HAD ALMOST
SIGNIFICANT WORSENING IN THEIR
MORTALITY BUT NOT QUITE
SIGNIFICANT, .088.
SO AGAIN, THIS IS A POST HOC
ANALYSIS, BUT IT'S VERY
INTERESTING BECAUSE IT GOES
ALONG WITH SOME OF OUR OTHER
POST HOC ANALYSES, SUGGESTING
THAT THOSE INDIVIDUALS WHO LOST
THE MOST WEIGHT IN ILI, 10% OR
MORE, DID SHOW BENEFICIAL
EFFECTS RELATIVE TO DSE AS A
WHOLE.
AND THAT THOSE INDIVIDUALS WHO
GAINED WEIGHT MAY HAVE HAD A
SLIGHT WORSENING IN THEIR RISK.
NOW FINALLY, IN ANOTHER RECENT
MANUSCRIPT THAT WE PUBLISHED IN
DIABETES CARE, WE EXAMINED WHAT
HAPPENED WITH WEIGHT OVER THE
FULL COURSE OF LOOK AHEAD.
SO NOW LOOKING AT WEIGHT CHANGES
PARTICULARLY DURING THE POST
INTERVENTION PERIOD.
AS YOU CAN SEE HERE, BOTH ILI
AND DSE LOST WEIGHT OVER THE
LAST SIX TO 10 YEARS OF THE
STUDY.
WE USE TRAJECTORY ANALYSES TO
DETERMINE IF THERE WERE
DIFFERENT PATTERNS OF WEIGHT
CHANGES AFTER THE END OF
INTERVENTION.
THIS ANALYSIS IDENTIFIED FOUR
DIFFERENT TRAJECTORIES.
GAINERS, A STABLE GROUP, A
STEADY LOSS GROUP, AND A STEEP
LOSS GROUP.
THE STEEP LOSS GROUP INCLUDED
ONLY 10% OF THE PARTICIPANTS.
BUT I WANT TO POINT OUT HOW
STEEP THEIR WEIGHT LOSSES WERE.
ON AVERAGE, THESE INDIVIDUALS
LOST ALMOST 20% OF THEIR BODY
WEIGHT OVER THE EIGHT YEARS FROM
YEAR EIGHT TO 16.
THAT'S FAR GREATER THAN WE
ACHIEVED WITH OUR ILI PROGRAM
DURING THE ORIGINAL
INTERVENTION.
WE ALSO FOUND THAT THESE STEEP
LOSER, THESE 10% OF THE GROUP,
HAD AN INCREASED RISK OF
MORTALITY.
30% OF THESE INDIVIDUALS PASSED
AWAY, VERSUS 10 TO 19% IN OUR
OTHER THREE GROUPS.
THEY WERE ALSO OLDER, SICKER,
AND THEY REPORTED LESS USE OF
HEALTHY WEIGHT LOSS STRATEGIES.
SO THESE DATA SUGGEST TO US THAT
PERHAPS THEIR WEIGHT LOSSES WERE
UNINTENTIONAL, NOT INTENTIONAL.
AGAIN, SUGGESTING THAT
UNINTENTIONAL WEIGHT LOSS MAY
HAVE A NEGATIVE EFFECT ON
HEALTH, EVEN IF INTENTIONAL
WEIGHT LOSS IS HELPFUL.
SO IN CONCLUSION, ILI HAD NO
EFFECT ON SEVERAL IMPORTANT
THINGS, INCLUDING THE PRIMARY
OUT COME OF CVD.
IT ALSO HAD NO EFFECT ON CANCER,
COGNITION OR MORTALITY.
HOWEVER, ILI HAS HAD A POSITIVE
EFFECT ON MANY HEALTH ISSUES,
INCLUDING DIABETES REMISSION,
CHRONIC KIDNEY DISEASE, SLEEP
APNEA, AND OTHERS THAT I DIDN'T
EVEN DISCUSS.
THESE POSITIVE EFFECTS WERE
OFTEN GREATEST AT YEAR ONE AND
DIMINISHED OVER TIME.
THERE WAS HETEROGENEITY IN THE
RESPONSE TO ILI RELATIVE TO DSE.
ILI HAD A POSITIVE IMPACT IN
THOSE WHO WERE HEALTHIEST AT
BASELINE.
AND IN THOSE WHO LOST GREATER
THAN 10% OF THEIR BODY WEIGHT AT
ONE YEAR.
SO NOW I WANT TO RETURN TO MY
ORIGINAL QUESTION, SHOULD OLDER
ADULTS WITH DIABETES AND OBESITY
BE ENCOURAGED TO LOSE WEIGHT?
MY ANSWER, AND I WANT TO POINT
OUT THAT THIS IS MY ANSWER, NOT
EVERYONE WILL AGREE, IS YES, I
THINK THEY SHOULD BE ENCOURAGED.
BECAUSE GIVEN THE MANY
OUTCOMES OF WEIGHT LOSS IN THESE
OLDER INDIVIDUALS, I BELIEVE
CONTINUING TO RECOMMEND WEIGHT
LOSS IS APPROPRIATE.
HOWEVER, I THINK WE NEED TO BE
RECOMMENDING INTENTIONAL WEIGHT
LOSS AT APPROPRIATE RATES, AND
THAT OLDER, SICKER PATIENTS WHO
ARE LOSING WEIGHT TOO RAPIDLY,
SHOULD RAISE OUR CONCERNS.
NOW FOR MORE INFORMATION ABOUT
THESE STUDIES OR FOR MORE
INFORMATION ABOUT OUR TRIAL LOOK
AHEAD, I WOULD ENCOURAGE YOU TO
LOOK AT THIS RECENT ARTICLE I'VE
PUBLISHED IN OWE OBESITY, WHIH
REALLY SUMMARIZED MANY OF THE
FINDINGS FROM THE LOOK AHEAD
RANDOMIZED TRIAL AND INCLUDES
ALL THE DATA I WAS TALKING ABOUT
TODAY AND ALL THE REFERENCES FOR
WHAT I WAS TALKING ABOUT TODAY.
THERE'S ALSO THE
WWW.LOOKAHEADTRIAL.ORG WEBSITE
WHICH INCLUDES THE PROTOCOL FOR
THE DIFFERENT PHASES OF LOOK
AHEAD AND THE FULL BIBLIOGRAPHY.
AND FINALLY, WE'VE BEEN PUTTING
ALL OF OUR DATA GRADUALLY ON THE
NIDDK WEBSITE ON THE REPOSITORY,
AND WE'VE BEEN SENDING BLOOD
SAMPLES TO THE NIDDK REPOSITORY.
SO THOSE WILL ALL BE AVAILABLE
TO INVESTIGATORS WITHIN LOOK
AHEAD OR OUTSIDE OF LOOK AHEAD,
WHO WANT TO PROPOSE NEW USES OF
OUR DATA, NEW PROJECTS, OR NEW
USES OF OUR SAMPLES.
SO FOR EXAMPLE, WE HAD A GWAS OF
PARTICIPANTS.
I DID NOT GO INTO ANY OF THE
GENETIC ANALYSES IN MY FINDINGS
TODAY, BUT THEY ARE ALL
AVAILABLE IF YOU WANT TO GO TO
THIS REPOSITORY.
SO I JUST WANT TO END BY
THANKING YOU ALL AND
PARTICULARLY THANKING THE OFFICE
OF DISEASE PREVENTION FOR
SUGGESTED ME AS A SPEAKER TODAY.
THANK YOU.
>> THANK YOU, DR. WING, VERY
MUCH FOR A FASCINATING
PRESENTATION.
LOTS OF QUESTIONS TO CONSIDER.
AND WE HAVE A LITTLE TIME TO DO
THAT.
SO LET ME START.
WHY WOULD OBSERVATIONAL STUDIES
SHOW HIGHER MORTALITY AND WEIGHT
LOSS WHERE A TRIAL LIKE LOOK
AHEAD SHOWED MANY HEALTH
BENEFITS FROM WEIGHT LOSS?
>> I BELIEVE THAT'S REALLY
BECAUSE OF THE PROBLEM OF
DISTINGUISHING INTENTIONAL
VERSUS UNINTENTIONAL WEIGHT
LOSS.
SO IN AN OBSERVATIONAL STUDY YOU
HAVE A LOT OF PEOPLE LOSING
WEIGHT BUT YOU DON'T KNOW WHY OR
HOW.
IN A CLINICAL TRIAL, WHAT YOU'VE
DONE IS TAKE IN HALF THE PEOPLE
AND RANDOMLY ASSIGN THEM TO
INTENTIONALLY LOSE WEIGHT.
YOU'VE TAUGHT THEM HEALTHY
STRATEGIES TO DO IT, AND YOU'VE
FOLLOWED THEM OVER TIME.
SO I BELIEVE THAT THAT'S THE
DIFFERENCE.
IT'S IN THE METHODOLOGY AND THE
DESIGN OF THOSE TWO TYPES OF
STUDIES.
>> THANK YOU.
I SHOULD HAVE SAID THIS AT THE
BEGINNING OF THE QUESTION AND
ANSWER PERIOD BUT LET ME DO IT
NOW.
THE CODE FOR CONTINUING MEDICAL
EDUCATION CREDITS IS 37947.
SO THOSE OF YOU WHO ARE
INTERESTED IN THAT, 37947.
NOW, RETURNING TO QUESTIONS.
SOME PEOPLE HAVE SUGGESTED THAT
WE DON'T NEED TO DO THESE LARGE,
EXPENSIVE CLINICAL TRIALS
ANYMORE, THAT WE CAN INSTEAD USE
SOPHISTICATED CAUSAL MODELING
TECHNIQUES WITH FAR LESS
EXPENSIVE OBSERVATIONAL DATA TO
ANSWER THESE QUESTIONS.
WHAT'S YOUR VIEW?
>> I'VE HEARD THAT OFTEN TALKED
ABOUT WITH EMR DATA, SO FOR
EXAMPLE, TAKING A GROUP OF
PEOPLE AND THEN FOLLOWING THEM
THROUGH EMR DATA, BUT I WOULD
REALLY QUESTION THAT.
FIRST OF ALL, I WOULD QUESTION
HOW YOU'RE EVER GOING TO
DISTINGUISH THOSE PEOPLE WHO ARE
LOSING WEIGHT INTENTIONALLY AND
USING HEALTHY STRATEGIES, VERSUS
THOSE PEOPLE WHO ARE LOSING
WEIGHT UNINTENTIONALLY BECAUSE
THEY'RE ALREADY ILL.
SO YOU CAN TRY TO DO THAT BY
SAYING OKAY, LET'S LEAVE OUT
ANYBODY WHO'S A SMOKER, LET'S
LEAVE OUT ANYBODY WHO HAS CANCER
IN THE FIRST TWO OR THREE YEARS
AND LOOK AT THEIR MORTALITY
SUBSEQUENT.
THAT'S WHAT THEY'VE DONE IN
OBSERVATIONAL STUDIES BEFORE.
BUT I THINK THOSE ARE ALL STILL
OPEN TO CRITICISM BECAUSE THEY
REALLY CAN'T DISTINGUISH THE
TWO, INTENTIONAL VERSUS
UNINTENTIONAL WEIGHT LOSS.
>> OKAY.
LOOK AHEAD DID A GREAT JOB IN
RECRUITING MINORITY
PARTICIPANTS.
37% IN THE EARLY 2,000s IS
MUCH BETTER THAN A LOT OF OTHER
STUDIES THAT WERE UNDERWAY AT
THE SAME TIME.
HOW DID YOU MANAGE THAT?
>> THAT WAS A LOT OF WORK BUT IT
WAS GREAT.
WE ACHIEVED IT.
FIRST OF ALL, OUR SITES WERE
SELECTED TO BE ALL OVER THE
UNITED STATES.
SO WE HAD A SITE IN TEXAS THAT
WAS RECRUITING, WE HAD A SITE IN
BALTIMORE THAT WAS ABLE TO
RECRUIT A LOT OF AFRICAN
AMERICANS.
WE HAD A SITE IN L.A. THAT WAS
ABLE TO RECUTE A LOT OF
HISPANICS AND ACTUALLY TRANSLATE
A LOT OF THE MATERIAL INTO
SPANISH FOR THESE PARTICIPANTS.
AND NEW YORK HAD A SITE.
SO BY PUTTING SITES IN DIFFERENT
CENTERS AROUND THE COUNTRY, WE
WERE ABLE TO RECRUIT DIFFERENT
MINORITY GROUPS PLUS IN
ADDITION, THAT WAS A REAL GOAL
IN THE STUDY.
SO EVERYBODY WAS ENCOURAGED TO
TRY VERY HARD TO RECRUIT THOSE
MINORITY GROUPS.
>> IT CLEARLY WORKED.
>> I SHOULD HAVE ALSO MENTIONED
THAT WE ALSO HAD SITES WITH THE
INDIAN TRIBES, AND THAT THE
INDIAN HEALTH SERVICE ALSO
HELPED FUND THE STUDY.
>> GREAT.
LOOK AHEAD HAD A TARGET OF
175 MINUTES OF PHYSICAL
ACTIVITY.
WHAT KIND OF PHYSICAL ACTIVITY
QUALIFIED OR COUNTED TOWARDS
THAT 175 MINUTES?
>> I SHOULD POINT OUT, IT'S
175 MINUTES PER WEEK.
>> OKAY.
>> SO IT'S ABOUT 35 MINUTES EACH
DAY, YOU KNOW, FIVE DAYS A WEEK.
AND WHAT REALLY COUNTS IS
SOMETHING EQUIVALENT TO BRISK
WALKING.
AND THAT'S WHAT MOST OF OUR
PARTICIPANTS DID.
KEEP IN MIND OUR PARTICIPANTS
WERE 60 YEARS OLD WHEN THEY
STARTED THE STUDY, SO NOW ON
AVERAGE, THEY'RE IN THEIR 80s.
SO BRISK WALKING IS AN
APPROPRIATE TYPE OF EXERCISE AS
PEOPLE ARE AGING.
THEY DON'T NEED ANY EQUIPMENT,
THEY DON'T NEED ANY SPECIAL
PROGRAMS OR ANYTHING TO DO BRISK
WALKING.
SO THAT'S WHAT WE TYPICALLY
ENCOURAGE, THAT'S WHAT WE
ENCOURAGE IN DPP AND THAT'S WHAT
WE ENCOURAGED IN LOOK AHEAD TOO.
>> YOU MENTIONED THAT A
PARTICIPANT'S PHYSICIAN COULD
CHANGE THEIR MEDICATIONS DURING
THE TRIAL.
DID THAT APPLY TO METFORMIN AND
IN DPP?
I REALIZE THAT'S NOT LOOK AHEAD,
THAT WAS DPP.
WAS THAT POSSIBLE THERE OR --
AND MORE GENERALLY IN LOOK
AHEAD, HOW DID CHANGES IN
MEDICATIONS, HOW WERE THOSE
MONITORED AND DEALT WITH IN THE
ANALYSIS?
>> I WANT TO ANSWER THE LOOK
AHEAD ONE BECAUSE I CAN'T QUITE
REMEMBER ALL THE DETAILS OF THE
DPP STUDY, BUT IN LOOK AHEAD, I
CAN TELL YOU WHAT HAPPENED.
IN LOOK AHEAD, WE HAD A VERY
STANDARD ALGORITHM FOR
MODIFICATIONS IN THEIR DIABETES
MEDICATION DURING THE FIRST
PERIOD OF INTENSIVE LIFESTYLE
INTERVENTION.
SO FOR EXAMPLE, IF YOU HAVE A
PERSON ON INSULIN AND THEY'RE
GOING TO START TO LOSE WEIGHT
RAPIDLY OR HOPEFULLY NOT TOO
RAPIDLY BUT APPROPRIATELY, BHU
THEY ARE GOING TO BUT
THEY ARE GOING TO LOSE WEIGHT
QUICKLY AT THE BEGINNING, YOU
DON'T WANT THEM TO STAY ON TOO
LONG -- WE HAD A VERY SPECIFIC
ALGORITHM AS TO HOW MUCH THEY
SHOULD CUT BACK THEIR INSULIN.
WE MONITORED THEIR BLOOD SUGAR
AND ADJUSTED THEIR MEDICATIONS.
SO THAT WAS THE ONLY PART OF THE
TRIAL WHERE WE AS A TRIAL WERE
DOING ANYTHING WITH MEDICATIONS.
THROUGHOUT THE REST OF THE
TRIAL, WE FELT THAT IT WAS MORE
APPROPRIATE FOR THE
PARTICIPANTS' OWN PHYSICIAN TO
BE MAKING ALL OTHER ADJUSTMENTS
IN THEIR MEDICATIONS.
SO THAT INCLUDED THEIR
ANTIHYPERTENSIVES, THEIR
STATINS, OR INSULIN OR ANY OTHER
MEDICATIONS FOR DIABETES OVER
TIME.
THAT WAS DONE IN PART FOR COST
REASONS BECAUSE IT WOULD HAVE
BEEN VERY EXPENSIVE IF WE HAD
TAKEN ON ALL THE MEDICAL
MANAGEMENT OF 5,000 INDIVIDUALS.
PLUS WE FELT THAT THAT WAS MORE
THE WAY THAT IT SHOULD BE DONE
IN A CLINICAL TRIAL SUCH AS
THIS.
NOW THAT'S A QUESTION THAT CAN
COME BACK AND HAUNT US A LITTLE
BIT NOW AND IS SOMETHING THAT WE
CAN CERTAINLY DISCUSS IF YOU
WOULD LIKE.
>> WHAT WERE THE BENEFITS OF THE
INTERVENTION IN DIFFERENT RACIAL
GROUPS?
I'M TRYING TO REMEMBER -- YOU
HAD GOOD REPRESENTATION OF
MINORITY GROUPS BUT I DON'T
RECALL RESULTS IN YOUR
PRESENTATION BY RACE OR
ETHNICITY.
>> I DIDN'T ACTUALLY PRESENT IT
BECAUSE MOST OF OUR RESULTS DID
NOT DIFFER BY RACE/ETHNICITY.
A FEW OF THEM DID BUT MOST OF
OUR RESULTS DID NOT.
SO I HAVE NOT COVERED THOSE.
BUT THEY ARE COVERED, I THINK,
TO SOME EXTENT MORE IN MY REVIEW
PAPER AND CERTAINLY BY GOING
BACK AND CHECKING EACH OF THOSE
REFERENCES DEPENDING ON WHICH
OUT COME YOU'RE MOST INTERESTED
IN.
>> I THINK IT'S ACTUALLY A VERY
GOOD OUTCOME THAT YOU FOUND FEW
IF ANY DIFFERENCES AMONG RACIAL
OR ETHNIC GROUPS, WHICH MEANS
IT'S QUITE GENERALIZED, IT WORKS
FOR EVERYONE.
>> WE FOUND SLIGHT DIFFERENCES
IN WEIGHT LOSS INITIALLY AS IS
OFTEN FOUND WITH AFRICAN
AMERICANS LOSING LESS WEIGHT
THAN CAUCASIANS, WHITES, BUT
OVER TIME, EVERYBODY CAME
TOGETHER.
SO THAT OVER TIME, YOU DON'T SEE
BIG DIFFERENCES IN THE WEIGHT
LOSS OUTCOMES.
SO I THINK THAT WAS ONE.
INTERESTING FINDINGS.
>> HAS ANYONE PROPOSED THE
REBOUND OBSERVED IN WEIGHT GAIN
OR WEIGHT LOSS AND PHYSICAL
ACTIVITY EXERT NEGATIVE EFFECTS
FOR THE PRIMARY OUTCOMES OF THE
STUDY?
>> I CERTAINLY AGREE WITH THAT,
THAT CERTAINLY COULD BE PART OF
WHAT IS HAPPENING.
I'VE SHOWN YOU WHAT HAPPENED
WITH OUR WEIGHT LOSSES AND OUR
FITNESS.
WE GOT OUR BEST EFFECTS AT YEAR
ONE, WITH GRADUALLY DIMINISHING
EFFECTS AND TOWARDS THE END OF
THE STUDY, BOTH GROUPS WERE
LOSING WEIGHT.
SO ALL OF THOSE DIFFERENCES MAY
HAVE AFFECTED OUR OUTCOMES BUT
WE HAVE NOT DONE ANALYSES
LOOKING AT SPECIFICALLY WEIGHT
LOSS OR REGAINED OR SPECIFIC
PERIODS OF TIME.
LOTS OF DATA FOR ANYBODY THAT
WAS LIKE TO ANALYZE IT.
>> THAT'S A GOOD SEGUE TO THE
NEXT QUESTION.
YOU INDICATED THAT LOOK AHEAD IS
CONTINUING, EVEN 22 YEARS AFTER
IT BEGAN.
WHAT'S THE FUTURE OF THE STUDY?
>> IT'S NOW ENTIRELY BEING DONE
BY PHONE CALLS FROM THE
COORDINATING CENTERS.
SO WE ORIGINALLY HAD 16 SITES
BUT AT THIS POINT IN TIME, WE
CONVERTED TO JUST THE
COORDINATING CENTER CALLING ALL
OUR PARTICIPANTS.
AND WE WENT FROM ORIGINALLY
HAVING YEARLY VISITS WITH EACH
PATIENT TO DURING THE
OBSERVATIONAL PERIOD EVERY OTHER
YEAR VISITS WITH THE PATIENTS TO
NOW DOING IT ENTIRELY BY PHONE.
THAT'S PARTIALLY BECAUSE NOW
THAT THESE PATIENTS HAVE AGED,
IT'S MUCH, MUCH MORE DIFFICULT
TO GET THEM INTO THE CLINIC,
IT'S MUCH MORE DANGEROUS FOR
THEM TO TRY TO ARRIVE TO THE
CLINIC, FOR US TO GET THEM ON AN
EXAM TABLE, ET CETERA, ET
CETERA, ET CETERA.
SO FOR MANY REASON, WE MOVED THE
WHOLE STUDY TO BE A PHONE
CONTACT STUDY.
WE WILL BE FOLLOWING SOME OF THE
KEY OUTCOMES OF AGING, SO FOR
EXAMPLE, COGNITIVE FUNCTION WILL
BE ONE OF THE VERY IMPORTANT
OUTCOMES WITH ADJUDICATION AGAIN
OF DEMENTIA AND MILD COGNITIVE
IMPAIRMENT.
WE'RE ALSO FOLLOWING OTHER
PROBLEMS THAT ARE RELATED TO
OLDER INDIVIDUALS.
SO FOR EXAMPLE, DEPRESSION,
QUALITY OF LIFE, SLEEP PROBLEMS.
THERE'S A WHOLE BIG ANCILLARY
STUDY ON SLEEP THAT'S BEING
CONDUCTED.
AND THEN WE'RE ALSO WORKING WITH
DR. PETER HUCKFELT AT UNIVERSITY
OF MINNESOTA WHO IS ACCESSING
THE MEDICARE DATABASES AND WILL
BE ABLE TO LOOK AT HEALTH COSTS
AND HEALTH SAVINGS OVER THE
COURSE OF LOOK AHEAD, USING THE
MEDICARE DATABASES.
>> SOUNDS LIKE THERE'S LOTS OF
OPPORTUNITY FOR NEW WORK.
WITH THE TRANSITION TO THIS
TELEPHONE OPERATION, IT RAISES
QUESTIONS ABOUT RELYING ON SELF
REPORT DATAVERSE US DATA
DIRECTLY COLLECTED ON BEHALF OF
THE STUDY.
THAT WOULD APPLY TO SOME
VARIABLES, PERHAPS, LIKE WEIGHT
OR HEIGHT.
IT MIGHT NOT APPLY TO SOME OTHER
VARIABLES, I'M NOT SURE HOW YOU
MEASURE COGNITIVE FUNCTIONING
OVER THE PHONE, BUT PERHAPS YOU
COULD ENLIGHTEN US.
>> SURE.
THERE ARE VERY GOOD STANDARDIZED
WAYS TO MEASURE COGNITIVE
FUNCTION OVER THE PHONE SO YOU
CAN ADMINISTER MANY OF THESE
COGNITIVE FUNCTION TESTS WITH
VALIDATED MEASURES OVER THE
PHONE WITH OLDER INDIVIDUALS.
IT'S BEING DONE IN OTHER TRIALS
AT THE MOMENT, WE'LL BE ADOPTING
THE SAME PROCEDURES IN OUR
TRIAL.
NOW MEASURING WEIGHT IS MORE
DIFFICULT.
SO AT THE MOMENT, WE ARE NOT
DOING ANYTHING TO MAKE CERTAIN
THAT OUR RESULTS ARE RELIABLE
FOR WEIGHT OR VALID FOR WEIGHT.
WE ARE USING SELF-REPORT.
HOWEVER, THAT'S BEEN AN AREA
WHERE MANY OF US HAVE TALKED
ABOUT DOING AN ANCILLARY STUDY,
WHERE WE COULD EITHER PROVIDE
SCALES WITH REMOTE CAPABILITIES
SO THAT THEY COULD DWSH WHEN THE
PERSON GOT ON THE SCALE, WE
COULD SEE THEIR WEIGHT, OR AT
LEAST HAVING PEOPLE TAKE
PICTURES OF THEMSELVES AS
THEY'RE WEIGHING THEIRSELVES.
>> I WOULD VOTE FOR THE
BLUETOOTH TECHNOLOGY.
>> YES.
IT'S BETTER IF WE CAN AFFORD IT.
>> YEAH, YEAH, AND YOU MIGHT BE
ABLE TO DO THAT IN A SUBSET.
>> EXACTLY.
WHAT WE'RE HOPING.
THE STUDY IS STILL ONGOING SO
THERE'S LOTS OF OPPORTUNITIES
FOR PEOPLE TO GET INVOLVED IN
THE STUDY.
EITHER AS I SAID LOOKING AT SOME
OF OUR DATA, LOOKING AT SOME OF
OUR BLOOD WORK OR PROPOSING
ANCILLARY STUDIES.
SO WE'RE VERY OPEN TO ANCILLARY
STUDIES GOING ON AT THIS TIME.
>> I WOULD THINK THAT ONE OF THE
BIGGEST FRUSTRATIONS FOR YOU AND
THE OTHER INVESTIGATORS WAS THE
REBOUND AFTER THE FIRST YEAR.
YOU HAD SUCH A GREAT EFFECT IN
THE FIRST YEAR, AND THEN THE
EFFECT AT LEAST FOR WEIGHT OR
PHYSICAL ACTIVITY DECLINED NOT
QUITE BACK TO BASELINE LEVELS
BUT CERTAINLY BACK IN THAT
DIRECTION.
WHAT CAN WE DO IN FUTURE STUDIES
TO TRY TO PREVENT THAT REA
BOUND?
REBOUND?
WOULDN'T IT BE FUND TO SEE WHAT
THE EFFECT OF THIS INTERVENTION
WAS, IF YOU CAN HOLD THAT?
>> I TOTALLY AGREE WITH YOU.
I HAVE BEEN WORKING ON THAT
PROBLEM FOR YEARS AND YEARS AND
YEARS.
WAY BEYOND THE 22 YEARS INVOLVED
IN LOOK AHEAD.
WE DON'T KNOW WHAT WE CAN DO.
SO SOME PEOPLE HAVE SUGGESTED
THAT IF WE EDIT A MEDICATION, IT
MIGHT HELP.
THERE'S DIFFERENT APPROACHES
THAT WE COULD POSSIBLY USE.
WE COULD HAVE TRIED MORE
AGGRESSIVE APPROACHES TO WEIGHT
LOSS OR HAVING PEOPLE HAVE
DIFFERENT APPROACHES.
SO OURS WAS A CALORIE-BASED
DIET.
MAYBE OVER TIME WE COULD HAVE
GONE TO A CARBOHYDRATE
RESTRICTED DIET, YOU KNOW,
CHANGING THE TYPE OF DIET MIGHT
HELP WITH VARIETY.
BUT I THINK ALL OF THOSE ARE
STILL GOING TO SHOW THIS WHAT I
LIKE TO CALL A CHECKMARK TYPE OF
PATTERN WHERE YOU GET YOUR BEST
RESULTS INITIALLY, AND THEN THEY
GRADUALLY REGAIN WEIGHT OVER
TIME.
SO THAT'S A CHECKMARK THAT
UNFORTUNATELY HAS CHARACTERIZED
EVERY BEHAVIORAL WEIGHT LOSS
STUDY THAT I KNOW OF, AND ONLY A
FEW OF THE DRUG STUDIES HAVE NOT
HAD THAT CHECKMARK PART TOO.
>> IT'S A CHALLENGE.
SO THIS STUDY AND OTHERS HAVE
SHOWN US THAT LIFESTYLE CHANGES
CAN HAVE HUGE POSITIVE EFFECTS.
HOW -- NOT JUST ON HEALTH BUT ON
COST OF HEALTHCARE.
HOW DO WE EDUCATE SOCIETY ABOUT
THAT WHEN PEOPLE ARE CONSTANTLY
BOMBARDED WITH CONTRARY MESSAGES
OVER SOCIAL AND OTHER MEDIA?
>> THAT'S VERY INTERESTING
QUESTION, I THINK IT'S A REALLY
PROVOCATIVE ONE, PARTICULARLY AT
THIS MOMENT BECAUSE THERE'S A
LOT OF EMPHASIS RIGHT NOW ON NOT
EMPHASIZING WEIGHT LOSS, THAT WE
SHOULD NOT BE FOCUSING ON
WEIGHT, WE SHOULD BE FOCUSING
ONLY ON HEALTH OUTCOMES.
HOWEVER, IF YOU TALK TO MOST
PATIENTS, THEY REALLY DO WANT TO
LOSE WEIGHT, NOT ONLY SHOW
IMPROVEMENTS IN THEIR DIABETES
OR THEIR HEART DISEASE.
THEY WANT TO ALSO SHOW IT ON THE
SCALE OR IN THEIR CLOTHES.
SO WE'RE IN A LITTLE BIT OF A
CONUNDRUM OF HOW WE DO THIS, HOW
WE EMPHASIZE BOTH WEIGHT LOSS
AND HEALTH ALL AT THE SAME TIME.
AND I THINK MANY OF US ARE
PUTTING OUR HEADS TOGETHER AND
THINKING ABOUT HOW DO WE BEST DO
THAT FOR OUR PATIENTS.
>> AS A CLOSING QUESTION, I
WOULD ASK, WHAT ADVICE YOU WOULD
GIVE TO A YOUNG INVESTIGATOR, A
POSTDOC, A GRADUATE STUDENT
WHO'S THINKING ABOUT A YEAR
FOCUSED ON HEALTH AND WEIGHT.
WHAT ARE THE QUESTIONS THAT ARE
IMPORTANT TO CONSIDER OVER THE
NEXT FIVE TO TEP 10 YEARS, AND
YOU DISCOURAGE SOMEONE, WOULD
YOU ENCOURAGE THEM?
WHAT ADVICE WOULD YOU OFFER?
>> I THINK THAT'S A GREAT
QUESTION.
I WOULD STRONGLY ENCOURAGE THEM,
BECAUSE I THINK THIS IS STILL A
BURNING PROBLEM IN OUR COUNTRY.
I MEAN, IT'S SO PROMINENT, IT'S
SO MUCH ON EVERYBODY'S MIND.
AND WE STILL DON'T KNOW WHAT TO
DO.
I THINK AS YOU POINTED OUT THAT
FACT THAT THERE IS SO MUCH
REGAIN IS A PROBLEM.
AND IT'S ONE THAT WE HAVE TO
WORK ON AND TRY TO SOLVE.
BUT AS OF YET, I DON'T BELIEVE
WE'VE CRACKED THAT.
I WOULD ALSO ARGUE THAT THERE'S
SO MANY QUESTIONS THAT COULD
STILL BE TACKLED.
LIKE WHY IS WEIGHT LOSS SO
EFFECTIVE FOR SOME PEOPLE, WHY
ARE SOME PEOPLE ABLE TO COME
INTO THE SAME PROGRAM AND LOSE
WEIGHT AND OTHERS CANNOT?
WE KNOW THAT ON DAY ONE, SOME
PEOPLE -- IF I TALK TO A GROUP
OF PATIENTS ABOUT TO START A
PROGRAM, I CAN TELL THEM AHEAD
THAT SOME OF YOU ARE GOING TO DO
GREAT, SOME OF YOU ARE GOING TO
DO TERRIBLY, BUT I CAN'T FOR THE
LIFE OF ME TELL YOU WHO'S WHO.
NOTHING WE HAVE BEEN ABLE TO
FIGURE OUT IN TERMS OF
BEHAVIORAL, PSYCHOLOGICAL,
GENETIC PREDICTORS REALLY HAS
TOLD US THE ANSWER TO THAT.
THERE'S GOT TO BE SOME WAY TO
FIGURE OUT AHEAD WHO IS GOING TO
LOSE WEIGHT ON THIS PARTICULAR
PROGRAM AND WHO IS NOT.
AND THEN BE ABLE TO TELL
PARTICIPANTS THAT.
THIS WOULD BE A GOOD PROGRAM FOR
YOU OR NOT A GOOD PROGRAM FOR
YOU.
WE CAN'T DO THAT.
YEARS AND YEARS AGO, WHEN I WAS
FIRST STARTING MY OWN CAREER IN
RESEARCH ON OBESITY, A GENTLEMAN
CAME UP TO ME WHO SAID TO ME --
HE WAS STUDYING DRUGS AND HE
SAID TO ME, RENA, WE KNOW WE'RE
ON THE CUSP OF GETTING DRUGS.
WE JUST WANT TO YOU DO THE
PHENOTYPES.
BECAUSE IF YOU TELL US WHO
YOU'VE GOT, WE'LL BE ABLE TO
GIVE YOU A DRUG THAT MATCHES
THAT PERSON.
SO IF YOU HAVE A PERSON WHO'S
GOT OVEREATING PROBLEMS, WE'LL
GIVE YOU THAT DRUG AND IF
THEY'VE GOT A LOW METABOLIC
RATE, WE'LL GIVE YOU ANOTHER
DRUG.
WELL, I'M STILL WAITING FOR THE
DRUG AND FOR THOSE ANSWERS.
HAVEN'T HAD THEM YET.
SO MEANWHILE, I WOULD ENCOURAGE
ANYBODY WHO WANTS TO KEEP
WORKING ON THIS PROBLEM AND
WORKING ON BOTH MEDICATIONS,
DRUGS, SURGERY, AND BEHAVIORAL
APPROACHES TO IT.
>> GREAT.
I THINK THAT'S TERRIFIC ADVICE,
AND I WANT TO THANK YOU VERY
MUCH FOR A TERRIFIC
PRESENTATION, FOR A GREAT
CONVERSATION HERE AT THE END
DEALING WITH MANY OF THE
QUESTIONS THAT CAME IN FROM OUR
AUDIENCE.
AND I WANT TO THANK
EVERYBODY FOR JOINING IN TODAY'S
GORDON LECTURE, AND PARTICULARLY
DR. RENA WING.
THANK YOU.