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<title>Diabetic Nephropathy</title></titleStmt>

<publicationStmt><distributor>BASE and Oxford Text Archive</distributor>


<availability><p>The British Academic Spoken English (BASE) corpus was developed at the

Universities of Warwick and Reading, under the directorship of Hilary Nesi

(Centre for English Language Teacher Education, Warwick) and Paul Thompson

(Department of Applied Linguistics, Reading), with funding from BALEAP,

EURALEX, the British Academy and the Arts and Humanities Research Board. The

original recordings are held at the Universities of Warwick and Reading, and

at the Oxford Text Archive and may be consulted by bona fide researchers

upon written application to any of the holding bodies.

The BASE corpus is freely available to researchers who agree to the

following conditions:</p>

<p>1. The recordings and transcriptions should not be modified in any


<p>2. The recordings and transcriptions should be used for research purposes

only; they should not be reproduced in teaching materials</p>

<p>3. The recordings and transcriptions should not be reproduced in full for

a wider audience/readership, although researchers are free to quote short

passages of text (up to 200 running words from any given speech event)</p>

<p>4. The corpus developers should be informed of all presentations or

publications arising from analysis of the corpus</p><p>

Researchers should acknowledge their use of the corpus using the following

form of words:

The recordings and transcriptions used in this study come from the British

Academic Spoken English (BASE) corpus, which was developed at the

Universities of Warwick and Reading under the directorship of Hilary Nesi

(Warwick) and Paul Thompson (Reading). Corpus development was assisted by

funding from the Universities of Warwick and Reading, BALEAP, EURALEX, the

British Academy and the Arts and Humanities Research Board. </p></availability>




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<item n="speechevent">Lecture</item>

<item n="acaddept">Medicine</item>

<item n="acaddiv">ls</item>

<item n="partlevel">UG2/PG</item>

<item n="module">Urinary System</item>




<u who="nm0454"> # <pause dur="0.3"/> now my name's <gap reason="name" extent="2 words"/> i'm a consultant nephrologist which means i'm a kidney doctor <pause dur="0.4"/> and i'm going to give you two talks this morning <pause dur="0.4"/> # both about forty-five minutes <pause dur="0.5"/> according to your books it should be glomerular disease then diabetes but just to confuse you we're doing it the other way round <pause dur="0.4"/> so we're going to do diabetes first <pause dur="0.3"/> and then glomerular disease <pause dur="1.2"/> and # last time i was asked to hand out handouts before the talk <pause dur="0.4"/> so i'm going to <event desc="passes out handouts" iterated="n"/> submit to your # <pause dur="0.4"/> your ways <pause dur="0.3"/> if you want to spread them around <pause dur="8.8"/> okay <pause dur="0.3"/> right <pause dur="0.2"/> sit down shush shush shush <pause dur="0.6"/> diabetes diabetic nephropathy <pause dur="4.9"/> actually can i have one of the handouts i might need to # <pause dur="0.7"/> refresh my memory <pause dur="2.9"/><event desc="takes handout from member of audience" iterated="n"/> thank </u><gap reason="break in recording" extent="uncertain"/> <u who="nm0454" trans="pause"> okay <pause dur="0.6"/> now <pause dur="0.4"/> why are we interested in diabetes and diabetic nephropathy <pause dur="1.6"/> you know by now my talk's interactive so if you don't answer i'll start picking on people <pause dur="0.4"/> so why are we interested in diabetes and diabetic

nephropathy <pause dur="0.5"/> is it just because you have an exam on the subject <pause dur="3.0"/> okay come on </u><pause dur="0.5"/> <u who="sm0455" trans="pause"> increases </u><u who="nm0454" trans="overlap"> anybody </u><u who="sm0455" trans="overlap"> morbidity and mortality </u><pause dur="0.4"/> <u who="nm0454" trans="pause"> sorry </u><u who="nm0454" trans="latching"> increases morbidity and mortality </u><u who="nm0454" trans="overlap"> yeah very good so diabetes is very bad for you it's also very common how common is it </u><pause dur="0.8"/> <u who="sf0456" trans="pause"> think it's one in five </u><pause dur="0.4"/> <u who="nm0454" trans="pause"> speak up </u><pause dur="0.4"/> <u who="sf0456" trans="pause"> one in five </u><pause dur="1.0"/> <u who="nm0454" trans="pause"> one in five <pause dur="0.4"/> well <pause dur="0.6"/> actually in some bits of the world you're right <pause dur="0.4"/> in some bits of Australia <pause dur="0.2"/> New Zealand and other countries it's <pause dur="0.2"/> it is probably one in five but it's <pause dur="0.2"/> it's probably about two per cent <pause dur="0.5"/> of <pause dur="0.6"/> the general population in the U-K <pause dur="0.3"/> five per cent of blacks and Asians so it makes it <pause dur="0.2"/> with schizophrenia rheumatoid disease one of the commonest chronic diseases <pause dur="0.4"/> and therefore <pause dur="0.2"/> #

just by chance one or two of you in this room should have diabetes <pause dur="1.4"/> okay <pause dur="0.3"/> so it's a very common disease <pause dur="0.3"/> # you need to know a lot about it and that's going to be one of the themes of this talk <pause dur="0.4"/> the second talk is about rare diseases <pause dur="0.3"/> that you <trunc>ha</trunc> know have to know a lot about because it's in your exam but not just <pause dur="0.2"/> not because it's <pause dur="0.4"/> biologically more common or more important <pause dur="1.0"/> so <pause dur="0.4"/> diabetes is very common diabetic nephropathy <pause dur="0.3"/> is quite rare <pause dur="0.5"/> why why do you think it's quite rare <pause dur="0.2"/> lady at <kinesic desc="indicates member of audience" iterated="n"/> the end </u><pause dur="1.2"/> <u who="sf0457" trans="pause"> # </u><pause dur="1.8"/> <u who="nm0454" trans="pause"> if you don't know guess </u><pause dur="1.4"/> <u who="sf0457" trans="pause"> because it takes a long time to get to that stage </u><u who="nm0454" trans="overlap"> yeah very good i mean that's exactly the answer <pause dur="0.5"/> because it takes a very long time to get it <pause dur="0.3"/> and what implication <pause dur="0.4"/> # does that have for most most blacks and Asians <pause dur="0.2"/> why why is that such <pause dur="0.7"/> if you forget everything else <pause dur="0.2"/> that i'm going to say this morning just remember what this lady said so <pause dur="0.3"/>

diabetic nephropathy takes a long time to get <pause dur="0.7"/> and why is that so important </u><pause dur="0.4"/> <u who="sf0458" trans="pause"> <gap reason="inaudible" extent="1 sec"/> </u><u who="sf0457" trans="overlap"> they tend to get it earlier </u><pause dur="0.7"/> <u who="nm0454" trans="pause"> well they tend to get it earlier but not that early <pause dur="0.4"/> anybody else </u><pause dur="0.7"/> <u who="sf0459" trans="pause"> do they not get treated <pause dur="0.2"/> <gap reason="inaudible" extent="1 sec"/> </u><u who="nm0454" trans="overlap"> they're not get they don't get treated and it gets missed <pause dur="0.5"/> and why does why does <pause dur="0.2"/> chronic diabetes and diabetic nephropathy <pause dur="0.5"/> get missed <pause dur="2.6"/> it's not a trick question <pause dur="0.4"/> why do diseases get missed in general </u><pause dur="1.0"/> <u who="sm0460" trans="pause"> 'cause they're asymptomatic </u><pause dur="0.3"/> <u who="nm0454" trans="pause"> it's asymptomatic and that's the problem <pause dur="0.4"/> so both diabetes and diabetic nephropathy and many other complications of diabetes <pause dur="0.3"/> are asymptomatic these are so-called silent killers like hypertension <pause dur="0.8"/> and this is the problem with them they're very common <pause dur="0.2"/> they're very lethal <pause dur="0.2"/> and you'll miss them unless you look for them <pause dur="1.4"/> so there's some facts there down for you on the sheet <pause dur="0.3"/> # i've

said at the top eighteen per cent of patients in the U-K <pause dur="0.2"/> on dialysis have diabetes and that's true from the latest data <pause dur="0.3"/> <unclear>generally</unclear> you go to renal-reg-dot-com where <pause dur="0.2"/> all British data is accumulated <pause dur="0.3"/> fascinating for <pause dur="0.2"/> us nerdy <pause dur="0.3"/> nephrological types <pause dur="0.5"/> # <pause dur="0.4"/> so <pause dur="0.2"/> it's a common cause of a rare disease which makes it rare <pause dur="0.4"/> but nonetheless it's going to be the focus of the talk this morning <pause dur="1.1"/> # <pause dur="1.1"/> let's get back to basics as John Major once said and let's get into a few definitions <pause dur="0.4"/> so <pause dur="0.2"/> # i've got a definition of diabetic nephropathy down there for you <pause dur="0.2"/> as you can see it's a rather vague one <pause dur="0.5"/> it's i'll read it out to you <pause dur="0.3"/> it's <pause dur="0.3"/> a usually progressive renal disease <pause dur="0.2"/> secondary to <pause dur="0.4"/> diabetes <pause dur="0.6"/> and what's wrong with that definition <pause dur="1.6"/><kinesic desc="writes on board" iterated="y" dur="3"/> why is it so difficult to define <pause dur="3.3"/><kinesic desc="indicates member of audience" iterated="n"/> gentleman there why why is it so difficult to define <pause dur="0.3"/> something like diabetic nephropathy </u><pause dur="0.7"/> <u who="sm0461" trans="pause">

it presents in very different forms it can present in many different ways and can have many different causative </u><pause dur="0.6"/> <u who="nm0454" trans="pause"> very good </u><u who="sm0461" trans="overlap"> <gap reason="inaudible" extent="1 sec"/> </u><u who="nm0454" trans="overlap"> very good so it can present in many different ways there are many different forms there are many different causes and when you've got a complicated disease like that it's not like a myocardial infarction <pause dur="0.2"/> which you can define in terms of a C-K rise <unclear>dropped T</unclear> <pause dur="0.3"/> typical symptom signs <pause dur="0.3"/> this is a vague concept <pause dur="0.4"/> and i'll explain a bit later on why it's such a vague concept <pause dur="0.3"/> one of the more fundamental reasons why diabetic nephropathy is difficult to define is 'cause diabetes is difficult to define <pause dur="0.5"/> let's have a go gentleman here <pause dur="0.4"/> have a go at # defining diabetes </u><pause dur="0.3"/> <u who="sm0462" trans="pause"> # which one do you want <gap reason="inaudible" extent="1 sec"/> </u><u who="nm0454" trans="overlap"> # either <pause dur="0.2"/> or all <pause dur="0.3"/> speak up so everybody can hear </u><u who="sm0462" trans="latching"> it's when the pancreas <pause dur="0.2"/> isn't producing insulin </u><pause dur="0.5"/> <u who="nm0454" trans="pause"> or </u><pause dur="0.2"/> <u who="sm0462" trans="pause"> or when the <trunc>s</trunc> tissues aren't responsive to insulin </u><u who="nm0454" trans="latching">

very good that's actually probably the best definition i've heard from a <pause dur="0.2"/> a medical student it's # <pause dur="0.2"/> almost impossible to define i mean there are <gap reason="inaudible" extent="1 sec"/> definitions which are nice simple ones <pause dur="0.4"/> a fasting blood sugar of over </u><pause dur="0.7"/> <u who="ss" trans="pause"> seven </u><pause dur="0.2"/> <u who="nm0454" trans="pause"> seven <pause dur="0.2"/> and a random of over </u><u who="ss" trans="overlap"> eleven </u><pause dur="0.8"/> <u who="nm0454" trans="pause"> eleven okay <pause dur="0.3"/> so that's a nice simple one put it in the <trunc>bo</trunc> put it in the back of your brains useful in clinical practice <pause dur="0.3"/> at a deeper level of course diabetes is very difficult to define <pause dur="0.5"/> # and the gentleman there has probably come out with a pretty good one <pause dur="0.3"/> you know <pause dur="0.3"/> <shift feature="voice" new="mimicking northern English accent"/>it's trouble with pancreas <shift feature="voice" new="normal"/><pause dur="0.5"/> # <pause dur="0.2"/> you know either the pancreas doesn't make enough insulin or you can't respond to insulin <pause dur="1.1"/> if you want to have another go at defining it <pause dur="0.3"/> the typical group of symptoms and signs <pause dur="0.4"/> with a variety of causes <pause dur="0.7"/> associated <pause dur="0.3"/> with <pause dur="0.2"/> pancreatic trouble <pause dur="1.2"/> it's getting a bit vague now my

definition i'm running out of steam it's it's just impossible to define <pause dur="0.7"/> # in any <pause dur="0.2"/> concrete way because you've got gestational diabetes pregnancy-related diabetes <pause dur="0.4"/> is that diabetes it doesn't make you blind ten years later <pause dur="0.2"/> it's diabetes while you've got it <pause dur="0.8"/> so it is a very very difficult thing to define and it's quite interesting actually that one of the diseases that <pause dur="0.3"/> affects your whole course <pause dur="0.6"/> renal eyes heart everything is actually almost impossible to define <pause dur="0.5"/> and we could <pause dur="0.5"/> be defining it all wrong <pause dur="0.8"/> <trunc>b</trunc> <pause dur="0.2"/> what is the problem with the definition of diabetes related to absolute levels of of blood sugar <pause dur="6.0"/> what's the problem with that <pause dur="0.4"/> it's nice in a box back of the brain <pause dur="1.1"/> simple <pause dur="0.4"/> let us assume <pause dur="0.2"/> demonstrate it <pause dur="0.2"/> in the exams </u><pause dur="0.6"/> <u who="sf0463" trans="pause"> there's lots of variation in the range anyway </u><pause dur="0.3"/> <u who="nm0454" trans="pause"> yeah there's a lot of normal variation very good so <pause dur="0.4"/> by now you should realize that all normal ranges <kinesic desc="writes on board" iterated="y" dur="7"/> are a load of rubbish they're

all based on <pause dur="0.5"/> # <pause dur="0.2"/> the standard normal distribution so this could be height blood sugar <pause dur="0.2"/> et cetera et cetera and all normal ranges <pause dur="0.3"/> we take usually are two standard deviations from the mean <pause dur="0.3"/> so we say a normal blood sugar <pause dur="0.3"/> is what <kinesic desc="writes on board" iterated="y" dur="3"/> four to six <pause dur="0.3"/> and diabetes <pause dur="0.8"/> is a fastingness of seven <pause dur="0.2"/> or a random of over eleven <pause dur="0.2"/> but there's always going to be tail end Charlie <kinesic desc="writes on board" iterated="y" dur="1"/> who's quite normal who doesn't have diabetes <pause dur="0.6"/> but is has diabetes by a number definition <pause dur="0.9"/> and the other reason why it's so difficult to define of course <pause dur="0.3"/> is that the complications of diabetes <pause dur="0.3"/> are really the complications of what </u><pause dur="2.8"/> <u who="sm0464" trans="pause"> persistent hyperglycaemia </u><pause dur="0.3"/> <u who="nm0454" trans="pause"> speak up </u><pause dur="0.2"/> <u who="sm0464" trans="pause"> persistent hyperglycaemia </u><pause dur="0.3"/> <u who="nm0454" trans="pause"> # yeah yeah okay you're right but but <pause dur="0.2"/> what what <pause dur="0.6"/> what constellation of diseases <pause dur="1.0"/> large vessel diseases <pause dur="1.7"/> is <pause dur="0.9"/> the main <pause dur="0.3"/> problem <pause dur="0.8"/> with diabetes or one of the main problems with </u><pause dur="0.5"/> <u who="ss" trans="pause"> <gap reason="inaudible" extent="1 sec"/> </u><u who="nm0454" trans="overlap"> speak up </u><u who="sm0465" trans="latching">

ischaemic heart disease </u><u who="nm0454" trans="latching"> yeah ischaemic heart a part of atheroma <pause dur="0.6"/> and there is a danger <pause dur="0.2"/> of course that the large vessel complications of diabetes <pause dur="0.3"/> today we're going to talk about a small vessel complication of diabetes diabetic nephropathy <pause dur="0.7"/> but the large vessel complication of diabetes are atheroma <pause dur="0.5"/> and it's not impossible of course <pause dur="0.3"/> that <kinesic desc="writes on board" iterated="y" dur="18"/> we've all got our Venn diagrams mixed up <pause dur="0.7"/> and <pause dur="0.2"/> the <pause dur="0.3"/> atheroma Venn diagram <pause dur="0.3"/> is <pause dur="0.2"/> overlapping with the diabetes Venn diagram and of course it does 'cause diabetes <pause dur="0.2"/> does this but it's also possible <pause dur="0.3"/> that people with ischaemic heart disease people with <gap reason="inaudible" extent="1 sec"/> disease <pause dur="0.2"/> who happen to have <pause dur="0.3"/> a blood sugar of eight what's eight it's in the middle <pause dur="0.3"/> are labelled as having diabetes <pause dur="0.3"/> causing atheroma <pause dur="1.1"/> and i think <pause dur="0.4"/> there is so much overlap in what we now call Syndrome X which is this loose constellation of diabetes <pause dur="0.3"/> ageing hypertension atheroma <pause dur="0.2"/> eating

chips et cetera et cetera <pause dur="1.1"/> it is very very grey now <pause dur="0.5"/> nonetheless <pause dur="0.5"/> i've <pause dur="0.2"/> hopefully laid out a few rules for you a few simple rules but <pause dur="0.3"/> don't think about it's like most things in medicine if you think about it in too much detail <pause dur="0.6"/> it's all wrong <pause dur="0.5"/> and it's too complicated so just think about it simply <pause dur="1.4"/> okay <pause dur="0.2"/> so diabetes is difficult to define <pause dur="0.4"/> and therefore diabetic nephropathy is difficult to define but <pause dur="0.2"/> we have to <pause dur="0.2"/> work on some definitions <pause dur="0.3"/> we've talked a bit about <pause dur="0.4"/> # the prevalence already <pause dur="0.4"/> now <pause dur="0.9"/> how common is diabetic nephropathy on the sheet there <pause dur="0.2"/> i've put a few numbers for you <pause dur="0.3"/> i've said that <pause dur="0.2"/> forty per cent of people <kinesic desc="writes on board" iterated="y" dur="5"/> with IDDM <pause dur="0.8"/> and five per cent of people with NIDDM <pause dur="0.6"/> get diabetic nephropathy <pause dur="1.0"/> # <pause dur="1.3"/> again <pause dur="0.6"/> there's a lot of problem with all these numbers <pause dur="0.4"/> who's heard of <trunc>hea</trunc> of of linear bias <pause dur="1.2"/> any mathematicians <unclear>in the room</unclear> tell me about linear bias <pause dur="2.4"/> come on <pause dur="0.9"/> there's one of you deep down there <pause dur="0.4"/> <vocal desc="laughter" iterated="y" n="ss" dur="1"/> i know <pause dur="0.5"/> you read maths textbooks every night <pause dur="0.8"/> <vocal desc="laughter" iterated="y" n="ss" dur="2"/>

<unclear>this thick</unclear> you love it <pause dur="0.3"/><vocal desc="laugh" iterated="n"/><pause dur="0.5"/> come on <pause dur="0.3"/> linear bias <pause dur="1.6"/> well linear bias <pause dur="0.4"/> this is <gap reason="inaudible" extent="1 sec"/> i wasn't going to talk about it this morning but <pause dur="0.2"/> i was thinking about it in the car on the way here <pause dur="0.4"/> and i <trunc>s</trunc> <pause dur="0.5"/> # <pause dur="1.0"/> almost certainly decided to destroy my own talk <pause dur="0.4"/> linear bias <kinesic desc="writes on board" iterated="y" dur="2"/> affects the whole of medicine <pause dur="1.6"/> particularly chronic diseases but there are <pause dur="0.2"/> # some important there is some importance for <pause dur="0.2"/> acute diseases too <pause dur="0.4"/> okay so we've got these numbers we say <pause dur="0.3"/> X per cent of the population have Y A per cent of the population have B <pause dur="0.7"/> ten years later fifty per cent have cancer fifty per cent are dead <pause dur="0.7"/> where do these numbers come from <pause dur="0.5"/> where do they come from how do we develop these numbers <pause dur="0.8"/> <kinesic desc="indicates member of audience" iterated="n"/> lady on the end here </u><pause dur="1.4"/> <u who="sf0457" trans="pause"> # </u><pause dur="0.3"/> <u who="nm0454" trans="pause"> it's not a trick question <pause dur="0.8"/> if we said you know if i said to you <pause dur="1.4"/> fifty per cent of the population have <pause dur="0.5"/> diabetes <pause dur="0.3"/> where do you think that number comes from </u><pause dur="2.1"/> <u who="sf0457" trans="pause">

observing population <gap reason="inaudible" extent="1 sec"/></u><u who="nm0454" trans="overlap"> very good yes observing population <pause dur="0.2"/> cross-sectional analysis <pause dur="0.2"/> okay so taking a large population <pause dur="0.6"/> a hundred people a thousand people and and finding out who has diabetes <pause dur="1.0"/> but that's wrong isn't it because that's a <kinesic desc="writes on board" iterated="y" dur="1"/> snapshot <pause dur="0.5"/> it doesn't really tell you about the disease in the community <pause dur="1.3"/> and what you need to know <pause dur="0.5"/> in terms of <pause dur="0.2"/> how common is the disease now how common the disease was and how common the disease will be <pause dur="0.3"/> is actually nearly impossible to define <pause dur="0.3"/> so for example diabetes <pause dur="0.7"/><kinesic desc="writes on board" iterated="y" dur="3"/> we could take time X in the past <pause dur="0.6"/> nineteen-sixty-one when i was born <pause dur="0.3"/> long time ago <pause dur="0.6"/> # <pause dur="0.4"/> we define diabetes in a certain way <pause dur="0.2"/> and at that point we do a <kinesic desc="writes on board" iterated="y" dur="2"/> cross-sectional study and we say that one per cent of the population has diabetes <pause dur="1.4"/> time goes on <pause dur="0.2"/> and we say diabetes is bad

for you and leads to complications <pause dur="0.3"/> it leads to <pause dur="0.3"/><kinesic desc="writes on board" iterated="y" dur="1"/> X per cent of people getting diabetic nephropathy that's why i was thinking about it in the car on the way here <pause dur="0.3"/> X per cent of people forty per cent of IDDMs five per cent of NIDDMs <pause dur="0.3"/> getting the complications which <pause dur="0.2"/> must be over <kinesic desc="writes on board" iterated="y" dur="1"/> ten years by definition that's also on your sheets <pause dur="0.6"/> and so they're getting the complications there <kinesic desc="indicates point on board" iterated="n"/> so that's bad for you because <pause dur="0.2"/> if you wait long enough you'll get the complication of diabetes <pause dur="0.4"/> then <kinesic desc="writes on board" iterated="y" dur="1"/> something else might happen you may get <pause dur="0.3"/> <unclear>away</unclear> from small to large vessel complications then you may die <kinesic desc="writes on board" iterated="y" dur="1"/><pause dur="0.9"/> and then <pause dur="0.2"/> people can't do studies on you when you're <kinesic desc="writes on board" iterated="y" dur="1"/> dead <pause dur="0.9"/> but from that <pause dur="0.2"/> passage of time <pause dur="0.3"/> we draw all the conclusions that based all of our knowledge <pause dur="0.5"/> but remember most of the analysis is done <kinesic desc="writes on board" iterated="y" dur="2"/> at various times <pause dur="0.4"/> it's cross-sectional data <pause dur="0.2"/> about a linear disease <pause dur="0.2"/> and it could all be wrong <pause dur="0.3"/> these are not the same patients <pause dur="0.4"/> society has changed <pause dur="0.2"/> the

planet has changed the universe has changed in that time <pause dur="0.6"/> and our definitions of chronic disease so <pause dur="0.2"/> the definition of rheumatoid arthritis might be quite different <kinesic desc="writes on board" iterated="y" dur="1"/><kinesic desc="indicates point on board" iterated="n"/> then <pause dur="0.2"/> from <kinesic desc="writes on board" iterated="y" dur="1"/><kinesic desc="indicates point on board" iterated="n"/> then <pause dur="1.4"/> and if you think about it most chronic diseases have this problem with linear bias <pause dur="0.5"/> and <pause dur="0.4"/> the bias leads to what <trunc>wh</trunc> what does it make researchers do <pause dur="2.9"/> <kinesic desc="indicates member of audience" iterated="n"/> lady there in the blue <pause dur="0.9"/> researchers who don't understand linear bias <pause dur="0.5"/> what do they what what what <pause dur="0.3"/> is the danger that they do </u><pause dur="2.7"/> <u who="sf0466" trans="pause"> <gap reason="inaudible" extent="1 sec"/></u><u who="nm0454" trans="overlap"> what happens as you get older <pause dur="1.0"/> hair falls out go grey <pause dur="0.3"/> everything goes floppy <pause dur="0.8"/> what happens <pause dur="1.1"/> to your brain as you get older <pause dur="1.0"/> what do old what do me and <gap reason="name" extent="1 word"/> talk about when <pause dur="0.2"/> when we're out of here we're sick of you lot <vocal desc="laughter" iterated="y" n="ss" dur="1"/> you're always

late <pause dur="0.5"/> moaning your mobiles are on <pause dur="0.3"/> what are we <trunc>mo</trunc> <pause dur="0.4"/> what are we <pause dur="0.5"/> what do we moan about <pause dur="2.6"/> anybody </u><pause dur="1.9"/> <u who="sm0467" trans="pause"> how it used to be </u><pause dur="0.5"/> <u who="nm0454" trans="pause"> how things used to be yeah <pause dur="0.2"/> the golden age <vocal desc="laughter" iterated="y" n="ss" dur="4"/><pause dur="0.2"/> when things were better <pause dur="0.2"/> when medical students wore <pause dur="0.2"/> ties and had briefcases <pause dur="0.5"/> the good old days when we were good at football <pause dur="0.2"/> we won the World <trunc>c</trunc> ah yeah we won a World Cup <unclear>earlier</unclear> <vocal desc="laughter" iterated="y" n="ss" dur="1"/><pause dur="0.6"/> i hope you all watched it <pause dur="0.4"/> # <pause dur="1.8"/> yeah we talk about the good old days the bygone era the golden age when things were good <pause dur="0.6"/> and it's all <kinesic desc="writes on board" iterated="y" dur="1"/> claptrap isn't it <pause dur="0.2"/> it's all claptrap it's just me and <gap reason="name" extent="1 word"/> getting older it's your and you're getting older too <pause dur="0.2"/> and it's linear bias again <pause dur="0.2"/> we're talking about some <pause dur="0.4"/> bygone era which never existed <pause dur="0.4"/> you know <pause dur="0.2"/> because time moves on <pause dur="0.4"/> and all of our conclusions that we draw about ourselves and society and

diabetes and diabetic nephropathy <pause dur="0.4"/> have the problem of linear bias in them <pause dur="0.7"/> 'cause all you need to do is change the definition <pause dur="0.8"/> <kinesic desc="writes on board" iterated="y" dur="4"/> from say four to six <pause dur="0.3"/> for diabetes to four to seven or rheumatoid arthritis in another way <pause dur="0.2"/> to completely change <pause dur="0.5"/> the whole of <pause dur="0.2"/> Western medicine and and the knowledge that we <pause dur="0.3"/> pass on to you <pause dur="1.7"/> how do we get rid of it we can't get rid of it actually because it's it's it's <shift feature="voice" new="laugh"/>part <shift feature="voice" new="normal"/>of time it's part of the course of the universe and it it is impossible to get rid of <pause dur="0.4"/> and so the best we can come out with is generalizations made from cross-sectional studies <pause dur="0.6"/> the important thing from your perspective is to know that it goes on <pause dur="0.4"/> and therefore you should be nice and cynical about any form of <trunc>i</trunc> <pause dur="0.2"/> information any form of statistics <pause dur="0.3"/> that anybody puts in front of you <pause dur="1.6"/> so <pause dur="0.7"/> let's # <pause dur="0.3"/> throw away the rule book <pause dur="0.6"/> <shift feature="voice" new="laugh"/>and # <shift feature="voice" new="normal"/><pause dur="0.8"/> move on <pause dur="0.6"/> so we've got to give you some numbers # <pause dur="0.5"/> we've said # that <pause dur="0.3"/> # diabetic nephropathy does

exist it's a small vessel complication of diabetes <pause dur="0.4"/> it's much more common in IDDMs but IDDM is a much rarer disease than NIDDM so <pause dur="0.4"/> by definition therefore far more people with NIDDM <pause dur="0.5"/> and that's where the problem lies get diabetic nephropathy <pause dur="0.3"/> and most of our patients in <gap reason="name" extent="1 word"/> <pause dur="0.2"/> the typical <gap reason="name" extent="1 word"/> <pause dur="0.3"/> patient <pause dur="0.2"/> is a late middle-aged fat Asian or black <pause dur="0.3"/> NIDDM <pause dur="0.3"/> <vocal desc="laughter" iterated="y" n="ss" dur="1"/> who presents late and that is the problem they present late as the gentleman <pause dur="0.2"/> said earlier <pause dur="0.2"/> it is an asymptomatic disease <pause dur="1.7"/> okay <pause dur="0.5"/> onset of the disease # most of the small vessel complications of diabetes come on after ten years <pause dur="0.6"/> so tell me some small vessel complications <pause dur="0.2"/> <kinesic desc="indicates member of audience" iterated="n"/> gentleman on the end there other than diabetic nephropathy <pause dur="0.4"/> small vessel </u><pause dur="1.8"/> <u who="sm0468" trans="pause"> don't know </u><pause dur="0.6"/> <u who="nm0454" trans="pause"> lady next to him </u><pause dur="1.1"/> <u who="sf0469" trans="pause"> # is retinopathy <gap reason="inaudible" extent="1 sec"/> </u><u who="nm0454" trans="overlap">

retinopathy okay <pause dur="0.2"/> there's another one which is usually classed as a small vessel any anybody else know <pause dur="3.6"/> neuropathy <pause dur="0.5"/> neuropathy <pause dur="0.5"/> # <pause dur="0.3"/> anything small <pause dur="0.2"/> is a usually a small vessel complication large vessel are <trunc>com</trunc> are complications of atheroma <pause dur="0.5"/> brain <pause dur="0.2"/> peripheral vascular disease of the heart <pause dur="0.8"/> # <pause dur="0.4"/> <trunc>cu</trunc> that's all rubbish though isn't it <pause dur="0.8"/> i mean <pause dur="0.3"/> i mean it doesn't take a a rocket scientist to work out that big blood vessels <pause dur="0.4"/> <kinesic desc="writes on board" iterated="y" dur="4"/> get smaller don't they <pause dur="1.9"/> and branch off in capillaries et cetera <pause dur="0.4"/> so # <pause dur="0.2"/> the whole classification of the complications of diabetes of small and large vessels is completely arbitrary 'cause what's small and what's large <pause dur="0.2"/> but nonetheless we do attempt to classify it in that way <pause dur="0.4"/> clearly most patients will have problems with both <pause dur="0.6"/> and that's very important for diabetic nephropathy because <pause dur="0.3"/> as well as having diabetic

nephropathy <pause dur="0.3"/> a small vessel complication <pause dur="0.3"/> <kinesic desc="indicates member of audience" iterated="n"/> lady there with the baseball cap <pause dur="0.4"/> what else do you think might affect the kidney <pause dur="1.5"/><kinesic desc="shrugs shoulders" iterated="n" n="sf0470"/> as well as <pause dur="0.7"/> problems with the small vessels </u><pause dur="2.6"/> <u who="sf0470" trans="pause"> <gap reason="inaudible" extent="1 sec"/> <pause dur="0.6"/> <gap reason="inaudible" extent="1 sec"/> </u><pause dur="0.4"/> <u who="nm0454" trans="pause"> speak up sorry </u><pause dur="0.3"/> <u who="sf0470" trans="pause"> <gap reason="inaudible" extent="1 sec"/> </u><pause dur="0.8"/> <u who="nm0454" trans="pause"> i can't hear you sorry </u><pause dur="0.6"/> <u who="nm0454" trans="pause"> i don't know <vocal desc="laughter" iterated="y" dur="1"/> </u><u who="nm0454" trans="overlap"> okay lady next to her <pause dur="0.2"/> what else might affect the kidney <pause dur="0.3"/> in <trunc>diabete</trunc> other than the small vessel complications </u><pause dur="3.9"/> <u who="sf0471" trans="pause"> large vessels <gap reason="inaudible" extent="1 sec"/> </u><u who="nm0454" trans="overlap"> large vessels such as the </u><pause dur="0.9"/> <u who="sf0471" trans="pause"> renal artery </u><u who="nm0454" trans="overlap"> renal artery okay and so <pause dur="0.3"/> # if you've had diabetes for over ten years <pause dur="0.3"/> <kinesic desc="writes on board" iterated="y" dur="2"/> you've usually got trouble in the large vessels <pause dur="0.3"/>

and trouble in the small vessels <pause dur="0.4"/> # <pause dur="0.3"/> so <pause dur="0.4"/> diabetic nephropathy pure diabetic nephropathy <pause dur="0.3"/> is extremely unusual and most people have both <pause dur="0.9"/> and in fact <pause dur="0.2"/> there are other <pause dur="0.4"/> renal complications of diabetes <pause dur="0.2"/> they're listed down there for you just to <pause dur="0.3"/> # read a few of them out <pause dur="0.2"/> papillary necrosis which has other causes <pause dur="0.3"/> anyone like to tell me some other cause of papillary necrosis <pause dur="3.3"/> not fair as i'm sure you don't have a lecture on papillary necrosis <pause dur="0.6"/> fascinating disease actually <pause dur="0.3"/><vocal desc="clears throat" iterated="n"/><pause dur="1.9"/> the <pause dur="0.4"/> the papilli remember are part of a drainage system of the kidney these are the papilli <pause dur="0.7"/><kinesic desc="writes on board" iterated="y" dur="2"/> and they can fall off <pause dur="0.4"/> papillary necrosis <pause dur="2.1"/> sickle cell disease okay <pause dur="0.3"/> sickle cell disease and diabetes are <pause dur="0.2"/> two of the most important causes of <pause dur="0.4"/> of <pause dur="0.3"/> # papillary necrosis in this country but worldwide probably analgesic nephropathy are probably <pause dur="0.2"/> # as important in the developed country <pause dur="0.8"/> okay <pause dur="0.2"/> so diabetes can affect the kidney in many ways renal vascular diabetic nephropathy papillary necrosis <pause dur="0.2"/>

recurrent urinary <trunc>tr</trunc> <pause dur="0.2"/> tract infections are more likely to get <pause dur="0.2"/> contrast nephropathy <pause dur="0.3"/> after <pause dur="0.2"/> # an angiogram of any type <pause dur="1.4"/> one of the fascinating things about diabetic nephropathy <pause dur="0.5"/> and in fact all the complications of diabetes <pause dur="0.4"/> is <pause dur="0.4"/> the W question <pause dur="0.8"/> why <pause dur="1.0"/> followed by the H question <pause dur="1.2"/> which is how <pause dur="2.2"/> so <pause dur="0.4"/> you tell me <pause dur="2.1"/> how <pause dur="0.2"/> does diabetes damage the eyes <pause dur="0.3"/> the kidneys <pause dur="0.3"/> the nerves <pause dur="1.2"/> lady with the <kinesic desc="indicates member of audience" iterated="n"/> blue there <pause dur="0.2"/> third from the end </u><pause dur="1.8"/> <u who="sf0472" trans="pause"> # </u><pause dur="0.8"/> <u who="nm0454" trans="pause"> if you don't know give me a can you give me a calculated guess what <pause dur="0.2"/> what do you think the metabolic abnormalities in <pause dur="0.6"/> in diabetes might be </u><pause dur="3.4"/> <u who="sf0472" trans="pause"> there's lots of <gap reason="inaudible" extent="1 sec"/> under pressure if you're going to have <gap reason="inaudible" extent="1 sec"/> cirrhosis <gap reason="inaudible" extent="1 sec"/></u><u who="nm0454" trans="overlap"> very good i'm glad you said that actually 'cause <pause dur="0.4"/> the obvious thing to say is what you're obviously not a a lady of the obvious <pause dur="0.9"/> <vocal desc="laughter" iterated="y" n="ss" dur="1"/> what is

what is the obvious thing to say <pause dur="0.9"/> diabetes is characterized by <pause dur="0.8"/> quite </u><pause dur="0.5"/> <u who="ss" trans="pause"> <gap reason="inaudible" extent="1 sec"/> </u><u who="nm0454" trans="overlap"> hyper </u><pause dur="0.2"/> <u who="ss" trans="pause"> glycaemia </u><u who="nm0454" trans="overlap"> glycaemia <pause dur="1.1"/> and so the most likely cause of all the <pause dur="0.2"/> trouble <pause dur="0.3"/> is hyperglycaemia but <pause dur="0.3"/> there's a lot of research going on into the and of course nobody knows <pause dur="0.2"/> and the whole research department i don't know if it's a particular interest of of of </u><pause dur="0.2"/> <u who="nf0473" trans="pause"> me </u><u who="nm0454" trans="latching"> of # <gap reason="name" extent="1 word"/> or or or <pause dur="0.5"/> # <pause dur="1.0"/> research all over the U-K in physiology departments <pause dur="0.4"/> # is <unclear>obviously</unclear> is is <trunc>i</trunc> to these questions the why and the how questions <pause dur="0.4"/> how does diabetes do it <pause dur="0.8"/> of course nobody knows <pause dur="0.3"/> and <pause dur="0.2"/> a lot of research is now orientated towards pressure <pause dur="0.2"/> and it may be <pause dur="0.2"/> that the effects of blood pressure on small vessels are probably more important than hyperglycaemia <pause dur="0.2"/> there's lots of other theories <pause dur="0.2"/> insulin growth hormone <pause dur="0.2"/> cytokines just goes on and on and on <pause dur="0.3"/>

Brian Williams who's a professor of medicine in Leicester <pause dur="0.2"/> his whole research is oriented towards this area but it is quite interesting <pause dur="0.3"/> # <pause dur="0.2"/> that we haven't actually come that far since # Banting and Best <pause dur="0.3"/> who who were Banting and Best <pause dur="0.9"/> let's pick on somebody else lady in the <kinesic desc="indicates member of audience" iterated="n"/> black top there who were Banting and Bess </u><pause dur="1.1"/> <u who="sf0474" trans="pause"> they </u><u who="nm0454" trans="overlap"> have you heard of them </u><u who="sf0474" trans="overlap"> discovered insulin </u><pause dur="0.3"/> <u who="nm0454" trans="pause"> very good okay <pause dur="0.3"/> so even if you didn't know good <vocal desc="laughter" iterated="y" n="ss" dur="1"/> calculated guess <pause dur="0.4"/> # <pause dur="0.7"/> and # <pause dur="0.3"/> they they discovered well <pause dur="0.9"/> i don't know if they <trunc>d</trunc> discovered insulin they they they refined it perhaps <pause dur="0.4"/> # <pause dur="0.3"/> and # this story which <pause dur="0.2"/> i'm sure you're all familiar with of a medical student and a <pause dur="0.2"/> and a surgeon <pause dur="0.3"/> who were put on the task of finding out

what was the trouble in diabetes <pause dur="0.4"/> was it insulin could they refine insulin <pause dur="0.4"/> one of them i can't remember which one does anybody know <pause dur="1.2"/> Banting or Best one of them developed diabetes knew they were going to die 'cause in the the States they couldn't get <unclear>a patent on</unclear> insulin <pause dur="0.2"/> went off on a world tour <pause dur="0.4"/> # <pause dur="0.2"/> there were no mobiles no texting no e-mails <pause dur="0.3"/> he just assumed he was going to die on his world tour and then the other one refined insulin <pause dur="0.2"/> so had to have a ring round <pause dur="0.3"/> all the bars of <pause dur="0.3"/> Vienna and Paris you know find this drunken medical student <vocal desc="laughter" iterated="y" n="ss" dur="1"/> <pause dur="0.4"/> # <pause dur="0.2"/> and # <pause dur="0.2"/> just get them back get him back and say <pause dur="0.5"/> actually we've cracked it we've got insulin and here's an injection and they lived happily ever after no <pause dur="0.2"/> he lived for many years <pause dur="0.3"/> # <pause dur="0.2"/> <trunc>n</trunc> anybody know <pause dur="0.5"/> anybody know which one it was can't remember okay look it up Banting and Best <pause dur="0.6"/> # <pause dur="0.4"/> but we haven't actually come that much further since Banting and Best because we haven't answered <pause dur="0.4"/> the the W and the H questions for

diabetic nephropathy or any of the complications of diabetes <pause dur="0.7"/> and <pause dur="0.9"/> these are incredibly important questions because <pause dur="0.2"/> it's pretty unlikely we're going to be able to <pause dur="0.3"/> get at the factor that causes diabetes <pause dur="0.4"/> but we might be able to turn off some of the complications of diabetes if <gap reason="name" extent="1 word"/> can crack it in her in in in her lifetime <pause dur="0.9"/> okay <pause dur="1.5"/> bit of pathology <pause dur="0.4"/> # <pause dur="0.6"/> i know your course doesn't emphasize pathology <pause dur="0.2"/> and certainly <kinesic desc="writes on board" iterated="y" dur="6"/> i'm not going to emphasize it either because when i was a medical student they axed the pathology course which i thought was one of the best things they ever did <pause dur="0.5"/> # <pause dur="0.3"/> but you do need to know a little about it <pause dur="0.3"/> and # <pause dur="0.2"/> there are some characteristic findings of diabetic nephropathy <pause dur="0.6"/> we don't to be honest normally <pause dur="0.6"/> do a kidney biopsy on somebody with suspected diabetic nephropathy so in other words if they have <pause dur="0.3"/> renal problems and diabetes we assume <pause dur="0.3"/> by and large that it is diabetic nephropathy <pause dur="0.5"/> # and that can

be a dangerous assumption <pause dur="1.3"/> if you were to do a renal biopsy at the earliest stages you do see some <kinesic desc="writes on board" iterated="y" dur="2"/> characteristic abnormalities you see expansion of the mesangium you see <pause dur="0.3"/> # <pause dur="0.2"/> enlargement of the glomerular basement membrane <pause dur="0.3"/> but these are really non-specific and can be seen in other nephropathies such as membranous nephropathy <pause dur="0.7"/> there is a more specific lesion <pause dur="0.3"/> which <kinesic desc="writes on board" iterated="y" dur="1"/> all medical students know called the Kimmelstiel-Wilson lesion <pause dur="0.8"/> # <pause dur="0.3"/> and this is part of a <pause dur="0.2"/> so-called nodular glomerulosclerosis <pause dur="0.3"/> <kinesic desc="writes on board" iterated="y" dur="1"/> and it has a characteristic <pause dur="0.4"/> # lumpy appearance <pause dur="0.3"/> # i deliberately haven't brought any slides of it along <pause dur="0.4"/> # <pause dur="0.2"/> because that's going to be one of your tasks after this talk <pause dur="0.4"/> to go out and find out what a Kimmelstiel-Wilson lesion looks like <pause dur="0.4"/> and # if you're really interested find out who Kimmelstiel and Wilson were <pause dur="0.4"/> but

again <pause dur="0.2"/> it's not that specific to diabetes <pause dur="0.2"/> and there are other renal diseases such as light chain <pause dur="0.4"/> deposition disease and other causes of these lumps <pause dur="0.4"/> of <pause dur="0.3"/> # <trunc>sclero</trunc> of nodular glomerulosclerosis <pause dur="0.9"/> okay <pause dur="0.5"/> so i've talked a bit about the pathogenesis we don't know the answers to the the how and the why question <pause dur="0.9"/> # <pause dur="0.4"/> having <pause dur="0.3"/> destroyed all your ideas <pause dur="0.3"/> of diabetes diabetic nephropathy linear bias the definition of disease statistics et cetera <pause dur="0.4"/> # i've put a nice little table in there for you 'cause then you can go away <pause dur="0.3"/> and assume that is completely correct <pause dur="0.3"/> and you can # <pause dur="0.2"/> regurgitate that <pause dur="0.3"/> <kinesic desc="writes on board" iterated="y" dur="8"/> the so-called Mogensen classification <pause dur="0.4"/> of diabetic nephropathy <pause dur="0.4"/> # <pause dur="0.5"/> i don't know how useful it is but it is something that i would expect you to know about <pause dur="0.3"/> # <pause dur="0.4"/> and <pause dur="1.0"/> it <pause dur="0.2"/> Mogensen in nineteen <pause dur="0.3"/> can't remember when it was <pause dur="0.3"/> eighty-two came up with this classification of four stages of diabetic nephropathy <pause dur="0.4"/> and i just want to go through those <pause dur="0.2"/>

briefly with you <pause dur="0.6"/> # <pause dur="0.5"/> the first stage is perhaps one of the most interesting one <pause dur="0.9"/> and <pause dur="0.3"/> # i i've got no idea how they found this information out <pause dur="0.4"/> but apparently at the early stage of diabetic nephropathy <pause dur="0.2"/> you go through a hyperfiltration stage which is very similar to the <pause dur="0.2"/> first trimester of pregnancy <pause dur="0.5"/> # <pause dur="1.0"/> do you know <gap reason="name" extent="1 word"/> <pause dur="0.4"/><gap reason="inaudible" extent="1 sec"/> </u><pause dur="0.3"/> <u who="nf0473" trans="pause"> no </u><u who="nm0454" trans="overlap"> does anybody know <pause dur="0.2"/> have you done any research into diabetes <pause dur="0.3"/> for previous degrees <pause dur="1.5"/> no <pause dur="0.7"/> ah yes you do <pause dur="0.5"/> one of you knows you're just not telling me <pause dur="0.4"/> the the # <pause dur="0.4"/> i <trunc>d</trunc> <pause dur="0.3"/> i don't know how they found out and obviously they they had a very accurate way of measuring G-F-R in the earlier stages of diabetes and we're talking <pause dur="0.3"/> you know <pause dur="0.2"/> the first couple of years of diabetes <pause dur="0.5"/> # and if you measure G-F-R at this stage apparently it is increased 'cause the kidney <pause dur="0.2"/> hyperfiltrates and apparently actually enlarges <pause dur="0.3"/> there are very few causes of <pause dur="0.2"/> of renal enlargement does anybody know any others <pause dur="2.3"/> apart from

diabetes </u><pause dur="1.6"/> <u who="sm0475" trans="pause"> removal of the other kidney </u><pause dur="0.3"/> <u who="nm0454" trans="pause"> yeah very good actually yeah <pause dur="0.3"/> absolutely removal of the other kidney <pause dur="0.2"/> any any any <pause dur="0.2"/> any other that's about the only guaranteed thing <pause dur="0.3"/> course nobody knows the mechanism of how your body knows you've lost a kidney and <pause dur="0.2"/> how it knows to enlarge the other one <pause dur="0.4"/> other causes of # of of a <trunc>lar</trunc> <trunc>l</trunc> enlarging kidneys </u><pause dur="0.7"/> <u who="sf0476" trans="pause"> tumour </u><pause dur="0.4"/> <u who="nm0454" trans="pause"> speak up </u><pause dur="0.2"/> <u who="sf0476" trans="pause"> tumour </u><pause dur="0.3"/> <u who="nm0454" trans="pause"> tumour yeah no <pause dur="0.2"/> yes a bit <pause dur="0.2"/> i mean you get a big lump <pause dur="0.2"/> the whole kidney itself doesn't enlarge </u><u who="sf0477" trans="latching"> cysts </u><pause dur="0.3"/> <u who="nm0454" trans="pause"> cyst yes polycystic kidney disease but it <trunc>c</trunc> <pause dur="0.3"/> the actual renal tissue doesn't enlarge <pause dur="0.2"/> but sort of and sort of </u><pause dur="0.3"/> <u who="sm0478" trans="pause"> hypertension </u><pause dur="0.2"/> <u who="nm0454" trans="pause"> <trunc>hyper</trunc> no <pause dur="0.3"/> no <pause dur="0.2"/> <vocal desc="clears throat" iterated="n"/><pause dur="0.9"/> ameloid ameloid is a characteristic cause of <trunc>so</trunc> enlarging kidneys <pause dur="0.3"/> and some <gap reason="inaudible" extent="1 sec"/>

you were half right <pause dur="0.2"/> lymphoma and leukaemia <pause dur="0.3"/> # if they directly infiltrate the kidney can cause the kidneys to enlarge <pause dur="0.4"/> but there are relatively few causes # of of a large kidney <pause dur="0.4"/> # <pause dur="0.2"/> and most of them are impossible to detect as the changes are so small <pause dur="0.4"/> and you need very accurate <pause dur="0.3"/> # ultrasound technology <pause dur="0.9"/> okay <pause dur="0.3"/> the second stage it starts to get a <trunc>bot</trunc> bit more interesting <pause dur="0.5"/> the glomerular <pause dur="0.2"/> disease that i've described <pause dur="0.4"/> the if you were to do a biopsy at that point <pause dur="0.3"/> the mesangial enlargement <pause dur="0.3"/> the thickening of the glomerular basement membrane <pause dur="0.3"/> # starts happening <pause dur="0.3"/> # the patient is unaware of this <pause dur="0.4"/> the G-F-R is still more than it was <pause dur="0.3"/> there's still no protein in the urine they still have normal blood pressure <pause dur="0.4"/> and # the creatinine is is still normal <pause dur="0.8"/> # <pause dur="0.5"/> this is # a very important stage <pause dur="0.3"/> and # and and i think that <pause dur="0.2"/> we we very often or or too often maybe this is what Mogensen was getting at in his classification <pause dur="0.4"/> think about stage three <pause dur="0.3"/> as the starting point in diabetes

diabetic nephropathy which is the micro <pause dur="0.2"/> <trunc>albin</trunc> albuminuria stage <pause dur="1.3"/> tell me about microalbuminuria gentleman <kinesic desc="indicates member of audience" iterated="n"/> at the back there with the green <pause dur="0.5"/> on the on the right tell me about microalbuminuria <pause dur="1.2"/> or microalbuminuria <pause dur="0.3"/> can't say it </u><pause dur="0.2"/> <u who="sm0479" trans="pause"> # </u><pause dur="1.3"/> <u who="nm0454" trans="pause"> have you heard of the concept </u><pause dur="0.6"/> <u who="sm0479" trans="pause"> no <pause dur="0.4"/> but it's <pause dur="0.8"/> # </u><pause dur="1.8"/> <u who="nm0454" trans="pause"> i'll tell you what it is and this when i was a student i thought it was small albumin molecules </u><pause dur="0.2"/> <u who="sm0479" trans="pause"> that's what i said as well </u><u who="nm0454" trans="latching"> <shift feature="voice" new="laugh"/>yeah <shift feature="voice" new="normal"/><vocal desc="laughter" iterated="y" n="ss" dur="1"/> <pause dur="1.0"/> ah it's not actually <pause dur="0.4"/> ask somebody else <pause dur="0.3"/> <kinesic desc="indicates members of audience" iterated="n"/> two ladies at the back there <pause dur="0.8"/> what what do you think <trunc>micro</trunc> have you heard of the phrase microalbuminuria </u><pause dur="1.3"/> <u who="sf0480" trans="pause"> is it just an amount of <pause dur="0.2"/> protein </u><pause dur="0.6"/> <u who="nm0454" trans="pause">

speak up yep </u><u who="sf0480" trans="latching"> it's amount of protein in the blood <pause dur="0.7"/> <gap reason="inaudible due to overlap" extent="1 sec"/> </u><u who="nm0454" trans="overlap"> yeah yeah <pause dur="0.2"/> anybody want to expand on that </u><pause dur="0.5"/> <u who="sm0481" trans="pause"> does it mean you can see it in a microscope but not </u><pause dur="0.4"/> <u who="nm0454" trans="pause"> no no i mean that's what i <shift feature="voice" new="laugh"/>used to think isn't it <shift feature="voice" new="normal"/>it's not such a silly answer </u><pause dur="1.0"/> <u who="sm0482" trans="pause"> 'cause there's <unclear>some</unclear> albumin in the <trunc>bl</trunc> in in the blood </u><pause dur="0.7"/> <u who="nm0454" trans="pause"> no it's microalbuminuria so it's in the urine </u><pause dur="0.5"/> <u who="sm0483" trans="pause"> <unclear>is it</unclear> just small quantity of small amounts of microalbumin </u><u who="nm0454" trans="overlap"> very good small amounts of albumin in the urine <pause dur="0.2"/> and <pause dur="0.3"/> very small amounts which cannot be detected by <trunc>stick</trunc> dipstick testing <pause dur="0.4"/> are present in the early stage of diabetic nephropathy <pause dur="0.9"/> # <pause dur="0.2"/> in my second talk i'm going to talk more about dipstick testing and the <pause dur="0.2"/> reliability and unreliability of dipstick testing <pause dur="0.5"/> # <pause dur="0.3"/> and <pause dur="0.8"/> the importance of it is it's said to be the forerunner <pause dur="0.2"/> of <pause dur="0.3"/> full-blown diabetic nephropathy but it's more important than that because <pause dur="0.4"/> it's possibly the forerunner <pause dur="0.2"/> of <pause dur="0.2"/> all the small and large vessel complications of diabetes and possibly <pause dur="0.3"/> also <pause dur="0.3"/> the complications the large

vessel complications of diabetes <pause dur="0.7"/> in a non-diabetic <pause dur="0.3"/> in other words atheroma <pause dur="0.2"/> in somebody who doesn't have diabetes and there is evidence from the <pause dur="0.3"/> the Framingham study <pause dur="0.2"/> that microalbuminuria is one of the most important <pause dur="0.7"/> things you can measure in a human being when they're twenty <pause dur="0.2"/> if you want to find out whether they're going to be alive when they're forty <pause dur="1.0"/> # <pause dur="0.2"/> and <pause dur="0.2"/> it seems that the kidney can in some way <pause dur="0.2"/> show <pause dur="0.3"/> you know what's going to happen in the rest of your life <pause dur="0.5"/> # <pause dur="0.2"/> and so if you have significant amounts of microalbuminuria yours at your earlier stage <pause dur="0.2"/> you know <pause dur="0.2"/> smoke <pause dur="0.3"/> you might as well enjoy it <pause dur="0.3"/> it's very bad news microalbuminuria <pause dur="0.6"/> just <pause dur="0.3"/> anybody tell me about the Framingham study what's the Framingham study lady at the front <kinesic desc="indicates member of audience" iterated="n"/><pause dur="0.6"/> have you heard of it </u><u who="sf0484" trans="latching"> no </u><pause dur="0.4"/> <u who="nm0454" trans="pause"> lady next to her <pause dur="0.4"/> very important study landmark study still going on <pause dur="1.1"/> i'm going to pick on you <kinesic desc="indicates member of audience" iterated="n"/> again <pause dur="0.4"/> what </u><pause dur="0.4"/> <u who="sf0485" trans="pause"> i don't know either </u><u who="nm0454" trans="overlap"> any anybody anybody Framingham study </u><u who="sm0486" trans="overlap">

it's a big study in America where </u><u who="nm0454" trans="overlap"> yep </u><u who="sm0486" trans="overlap"> it <trunc>s</trunc> started since nineteen-sixty-four or something like that and it </u><u who="nm0454" trans="overlap"> yes </u><u who="sm0486" trans="overlap"> it's been following <pause dur="0.4"/> a group of people living in Framingham </u><pause dur="0.2"/> <u who="nm0454" trans="pause"> yes </u><u who="sm0486" trans="latching"> for different diseases </u><u who="nm0454" trans="latching"> yes <pause dur="0.3"/> absolutely okay <pause dur="0.3"/> so there's a small study <pause dur="0.3"/> # <pause dur="0.2"/> does he know all the stuff <kinesic desc="indicates member of audience" iterated="n"/> this bloke <pause dur="1.3"/><vocal desc="laughter" iterated="y" n="ss" dur="1"/> well <pause dur="0.9"/> # # proud of you <pause dur="0.4"/><kinesic desc="writes on board" iterated="y" dur="1"/> # and <pause dur="0.2"/> it it's an attempt to get rid of linear bias i mean i don't think they realized that when they set <trunc>i</trunc> set it up <pause dur="0.2"/> small town <pause dur="0.3"/><event desc="audience noise" iterated="y" dur="1"/> on the east coast shush <pause dur="0.2"/> east coast of the United States in Framingham <pause dur="0.3"/> where they took a cohort of people <pause dur="0.3"/> who traditionally didn't tend to move too much from Framingham a bit like Coventry people <pause dur="0.3"/> <vocal desc="laughter" iterated="y" n="ss" dur="4"/> they just stay there basically miserable might as well stay here and nowhere else to go and the train's rubbish <pause dur="0.3"/>

but the <pause dur="0.2"/> # <pause dur="0.2"/> and <trunc>f</trunc> for the people of Framingham tend to stay around <pause dur="0.2"/> it's not that large a group it's in the tens of thousands of people rather than <trunc>hun</trunc> and that's <pause dur="0.2"/> maybe also one of the reasons why the study worked and is still ongoing <pause dur="0.2"/> and they've been followed since the sixties <pause dur="0.4"/> and and and a lot of what we teach you <pause dur="0.3"/> about <pause dur="0.3"/> # the <pause dur="0.2"/> pathogenesis <pause dur="0.3"/> and the cause of atheroma and diabetes all comes from the Framingham study there's a massive website that's all about the Framingham study <pause dur="0.3"/> they're publishing papers every week <pause dur="0.4"/> # and and and and much <trunc>o</trunc> <trunc>o</trunc> of <pause dur="0.3"/> of traditional Western medicine actually comes from Framingham <pause dur="0.2"/> i don't think the people of Framingham realize that <pause dur="0.9"/> and what we know about microalbuminuria i don't know <pause dur="0.5"/> how they had the foresight in the early sixties <pause dur="0.3"/> to start looking for very small amounts of protein in the urine but they did <pause dur="0.5"/> and # and and this is a a very # clever idea <pause dur="0.8"/> the reason i emphasize the

first two stages is that i think <pause dur="0.2"/> that if we're going to do anything about diabetic nephropathy and anything about the other complications the retinopathy <pause dur="0.2"/> it's before Framingham <pause dur="0.3"/> it's before microalbuminuria it's when they're normal <pause dur="0.5"/> it's when they are <pause dur="0.2"/> the IDDMs <pause dur="0.2"/> are <pause dur="0.6"/> four <pause dur="0.5"/> are six <pause dur="0.2"/> are ten years old <pause dur="0.4"/> then you start them on an ACE inhibitor <pause dur="0.2"/> then you do what you need to do <pause dur="0.2"/> to stop them <unclear>from getting any</unclear> complications not when they're twenty not when they're thirty <pause dur="0.8"/> but there lies the rub <pause dur="0.2"/> because the majority of patients i said are NIDDMs and they present late <pause dur="0.4"/> they've had a blood sugar of eight for five years of nine for another five years <pause dur="0.2"/> then it's picked up on routine testing <pause dur="0.4"/> and it's all over by then <pause dur="0.3"/> the eyes are starting to go they they're in stage three more likely stage four of diabetic nephropathy <pause dur="0.2"/> there's nothing you can do <pause dur="0.3"/> so if you want to really help diabetics i think it's <pause dur="0.2"/> it's premicroalbuminuria or at least at microalbuminuria stage <pause dur="1.1"/> and this is

true for the not just for the kidneys but for the eyes and all the other complications <pause dur="0.9"/> okay <pause dur="0.2"/> so can we isolate specific patients to focus on <pause dur="0.6"/> well <pause dur="0.5"/> not really # <pause dur="0.3"/> race <pause dur="0.3"/> # black and Asian people are more likely to get the small vessel complications that <pause dur="0.2"/> they're more likely to get diabetes and they're more likely to get the bad diabetes <pause dur="0.8"/> there are strong genetic factors which <pause dur="0.3"/> # <pause dur="0.2"/> are probably polygenic and haven't really been worked out but <pause dur="0.2"/> there are certainly <pause dur="0.2"/> patients who are born with a predisposition to develop bad diabetes <pause dur="1.0"/> and this is one this is the counter-argument <pause dur="0.4"/> for being a touchy-feely person going out in the community <pause dur="0.2"/> starting all black and Asian people <pause dur="0.2"/> on an ACE inhibitor as soon as they're born <pause dur="0.3"/> <trunc>a</trunc> and that studies <pause dur="0.2"/> such as that have been done there were some islands on the north coast of Australia <pause dur="0.3"/> where <pause dur="0.4"/> people just couldn't get away and they put entire communities with and without <pause dur="0.4"/> # diabetes on ACE inhibitors <pause dur="0.2"/> and this is one of the few things you

can do for a diabetic <pause dur="0.4"/> and they've dramatically reduced the dialysis rates <pause dur="0.4"/> the mortality cardiac mortality <pause dur="0.4"/> # <pause dur="0.6"/> look it up <pause dur="0.6"/> northern Australia islands <pause dur="0.3"/> diabetic nephropathy <pause dur="0.3"/> # you'll find <pause dur="0.2"/> loads and loads of papers <pause dur="0.3"/> # <pause dur="0.2"/> and they're actually fascinating studies where you take an entire community <pause dur="0.4"/> and reduce their glomerular capillary pressure and see what happens <pause dur="0.2"/> and a lot happens <pause dur="1.1"/> the reason i emphasize this is i think that <pause dur="0.4"/> racial and family <pause dur="1.0"/> # predisposition to developing bad diabetes <pause dur="0.2"/> is probably the most important factor <pause dur="0.2"/> and that of course we can do nothing about you can't change your parents <pause dur="0.6"/> and it does seem that forty per cent or so of diabetics <pause dur="0.5"/> get <pause dur="0.7"/> bad diabetes including the eyes the kidneys et cetera and so if you were a cynic you'd say well why bother for those forty per cent 'cause they're <pause dur="0.2"/> buggered anyway <pause dur="0.3"/> # but nonetheless i think we have to # adopt a positive approach and try and treat <pause dur="0.2"/> the hundred <pause dur="0.3"/> # not not just the sixty <pause dur="1.0"/> # <pause dur="1.5"/> glycaemic control <pause dur="0.6"/>

oh God <pause dur="0.4"/> i've got to tell you about this haven't i <pause dur="0.5"/> this is one of the things that i've i've i i have to tell you about <pause dur="0.3"/> because you you'll be expected to regurgitate it but i don't particularly believe in myself <pause dur="0.5"/> # <pause dur="3.2"/> what's the Judaeo-Christian <pause dur="0.2"/> method of controlling people <vocal desc="laughter" iterated="y" n="ss" dur="1"/> </u><pause dur="1.8"/> <u who="sm0487" trans="pause"> <gap reason="inaudible" extent="1 sec"/> </u><pause dur="0.9"/> <u who="nm0454" trans="pause"> Islamic as well <pause dur="1.7"/> come on <pause dur="0.3"/> bit of politics <pause dur="1.4"/> how lady here <kinesic desc="indicates member of audience" iterated="n"/><pause dur="0.6"/> how do we control people in the <pause dur="0.6"/> Judaeo-Christian <pause dur="0.2"/> way </u><pause dur="0.3"/> <u who="sf0488" trans="pause"> you have <pause dur="0.7"/> one partner </u><pause dur="0.6"/> <u who="nm0454" trans="pause"> yeah <pause dur="0.3"/> yeah <pause dur="0.3"/> okay <pause dur="0.7"/> fair enough yeah <pause dur="0.2"/> i'm talking more about <pause dur="0.2"/> society how do we control society </u><u who="sf0488" trans="overlap"> well you don't marry your cousin you don't <pause dur="0.6"/> have children <gap reason="inaudible" extent="1 sec"/> family <vocal desc="laugh" iterated="n"/></u><u who="nm0454" trans="overlap"> mm yeah but a bit broader <pause dur="0.3"/> politics <vocal desc="laughter" iterated="y" n="ss" dur="2"/> cynicism i want </u><pause dur="0.7"/> <u who="sm0489" trans="pause">

indoctrination </u><pause dur="0.2"/> <u who="nm0454" trans="pause"> sorry </u><u who="sm0489" trans="latching"> indoctrination </u><u who="nm0454" trans="latching"> indoctrination </u><pause dur="0.6"/> <u who="sm0490" trans="pause"> fear </u><pause dur="0.4"/> <u who="nm0454" trans="pause"> fear ah fear <vocal desc="cough" iterated="n"/> that's how we control people <pause dur="0.2"/> in the Judaeo-Christian way isn't it fear <pause dur="0.4"/> the stick and the carrot <pause dur="0.5"/> # <pause dur="0.6"/> and <pause dur="0.2"/> if you're a good boy <pause dur="0.9"/> what happens </u><pause dur="0.4"/> <u who="sm0491" trans="pause"> you're rewarded </u><pause dur="1.1"/> <u who="nm0454" trans="pause"> you go to heaven <pause dur="1.1"/> <vocal desc="laughter" iterated="y" n="ss" dur="1"/> good things happen <pause dur="0.3"/> if you're a bad boy or girl <pause dur="1.0"/> it's very bad isn't it <pause dur="0.6"/> so <pause dur="0.2"/> if you're a good boy you get rewarded by stuff you do good things you don't eat chips you don't go to McDonalds you don't smoke you don't have <pause dur="0.3"/> God it's boring isn't it <pause dur="1.7"/> <vocal desc="laughter" iterated="y" n="ss" dur="1"/> and if you're a bad boy you do all those things and then bad things happen you have diabetes you get fat you eat chips and you go to McDonalds <pause dur="0.4"/> and it all goes horribly wrong <pause dur="1.3"/> and <pause dur="0.6"/> the problem <pause dur="0.6"/> with the Judaeo-Christian-Islamic <pause dur="0.3"/> method of controlling people is we extended it to medicine of course because you know

we're part <trunc>o</trunc> <pause dur="0.2"/> of this culture we can't get away from it <pause dur="0.4"/> so <pause dur="0.2"/> and this is true of all chronic diseases whether it's rheumatoid arthritis schizophrenia <pause dur="0.3"/> you're a bad boy you didn't take your tablets you didn't have electric shocks to the head you didn't have injections once a month so what's going to happen you go out you go kill people <pause dur="0.3"/> that's bound to happen <pause dur="0.4"/> # <pause dur="0.5"/> and <pause dur="0.5"/> we have linked it to diabetes as well and the classic way we've linked it is <kinesic desc="writes on board" iterated="y" dur="4"/> glycaemic control <pause dur="1.5"/> and for years decades it has been assumed <pause dur="0.3"/> that if <pause dur="0.5"/> the blood sugar is the bad thing in diabetes which it probably isn't it's probably the blood pressure <pause dur="0.7"/> # <pause dur="0.2"/> then if you have tight diabetic control you can prevent the complications <pause dur="1.2"/> and this was dogma in Western medicine for for decades <pause dur="0.3"/> # until what what landmark study <pause dur="4.2"/> not many studies you need to know about in detail but there are a couple in diabetes <pause dur="0.3"/> anybody <pause dur="2.6"/> <kinesic desc="writes on board" iterated="y" dur="7"/>

the D-C-C-T <pause dur="0.4"/> in nineteen-ninety-one New England Journal of Medicine <pause dur="0.8"/> the U-K-P-D-S <pause dur="1.6"/> B-M-J the Lancet look these up <pause dur="0.4"/> very important studies <pause dur="0.6"/> if you ever get me in a viva i'll ask you about them the reference the page number <pause dur="0.2"/><vocal desc="laughter" iterated="y" n="ss" dur="1"/> the exact number of <pause dur="0.3"/> patients in each study <pause dur="0.2"/> i will not forget <pause dur="0.2"/> okay <pause dur="0.3"/> so don't come across me in a viva and don't know both studies sideways those are landmark studies <pause dur="0.7"/> # <pause dur="0.6"/> and the bottom line is that the first study <pause dur="0.6"/> attempted to address <pause dur="0.6"/> the Judaeo-Christian concept <pause dur="0.3"/> of <pause dur="0.2"/> tight diabetic control <pause dur="0.5"/> leads to good result <pause dur="1.2"/> in IDDMs and the U-K-P-D-S done in the U-K <pause dur="0.2"/> did the same in NIDDMs <pause dur="0.4"/> and both studies i'm not going into them in detail today <pause dur="0.2"/><kinesic desc="writes on board" iterated="y" dur="2"/> have been interpreted or <pause dur="0.3"/> misinterpreted as being <pause dur="0.2"/> positive <pause dur="1.5"/> # <pause dur="0.3"/> in that the patients who achieved tight diabetic control <pause dur="0.2"/> had less complications <pause dur="1.0"/> and they did <pause dur="0.4"/> to an extent <pause dur="0.4"/> but the end points were all soft <pause dur="0.6"/> such as <pause dur="0.6"/> can anybody think of a soft end point in diabetic nephropathy or <pause dur="0.3"/> eye disease <pause dur="0.9"/> let's pick on somebody else

gentleman <kinesic desc="indicates member of audience" iterated="n"/> there <pause dur="0.2"/> if you were do a <trunc>s</trunc> design a study <pause dur="0.5"/> of <pause dur="0.3"/> does <pause dur="0.5"/> tight diabetic control prevent the complications <pause dur="0.4"/> and you wanted to look at the complications of <pause dur="0.7"/> diabetes such as nephropathy or eye disease <pause dur="0.4"/> what what would be a possible soft end point <pause dur="0.8"/> that you could look at <pause dur="0.4"/> # i i <pause dur="0.6"/> wishy-washy <pause dur="0.3"/> end point <pause dur="0.8"/> difficult to <pause dur="0.5"/> define and prove <pause dur="2.6"/> anybody else <pause dur="0.4"/> ladies up <kinesic desc="indicates member of audience" iterated="n"/> lady in the white there soft end point diabetes </u><pause dur="0.3"/> <u who="sf0492" trans="pause"> disturbance in vision </u><pause dur="0.4"/> <u who="nm0454" trans="pause"> yeah disturbance in vision would be a good one <pause dur="1.2"/> proteinuria <pause dur="0.3"/> rate of decline of <pause dur="0.2"/> renal failure <pause dur="0.3"/> lots just think about it there's lots of soft end points <pause dur="0.5"/> and the soft end points <pause dur="0.2"/> were affected by tight diabetic control <pause dur="0.2"/> so there is some evidence of tight diabetic control <pause dur="0.5"/> but # if you look at the studies <pause dur="1.1"/> and i stress i will ask you about them if i ever meet you in a viva <pause dur="0.4"/> # <pause dur="0.5"/> and i will

create hell if you don't know about them <pause dur="0.8"/> # <pause dur="1.6"/> the hard end points weren't there <pause dur="0.4"/> death <pause dur="0.3"/> dialysis chop your legs off blindness they weren't there there was no significant improvement <pause dur="0.4"/> in the hard end points <pause dur="0.2"/> now you can say # back to linear bias well what does that <pause dur="0.3"/> what does that <kinesic desc="writes on board" iterated="y" dur="3"/> matter that you don't stop people from from dying <pause dur="0.4"/> # <pause dur="0.4"/> # and you don't <pause dur="0.4"/> # chop their legs off if you can delay <kinesic desc="writes on board" iterated="y" dur="1"/> chopping their legs off <pause dur="0.9"/> by a year <pause dur="0.5"/> then that's a good thing <pause dur="0.2"/> obviously <pause dur="0.6"/> but that wasn't proven either <pause dur="0.8"/> # <pause dur="0.2"/> because the study didn't really incorporate this problem of linear bias into it <pause dur="0.3"/> now but these are the best studies that we have and they are landmark studies <pause dur="0.4"/> and and you should know about them <pause dur="2.4"/> okay <pause dur="0.4"/> # <pause dur="1.0"/> they well probably <pause dur="0.5"/> several hundred people's life work <pause dur="0.2"/> so i shouldn't <shift feature="voice" new="laugh"/> knock them too much <shift feature="voice" new="normal"/><pause dur="0.3"/> # <pause dur="0.3"/> you know these were tens of thousands of patients putting them in in into into both studies <pause dur="0.4"/> and they are the the best data that we have <pause dur="0.4"/>

but look at them critically <pause dur="1.4"/> as just out of interest apart from <pause dur="0.3"/> get away from my ideas of <pause dur="0.3"/> the Judaeo-Christian method of controlling people what <pause dur="0.2"/> what <trunc>wh</trunc> why why do you think <pause dur="0.4"/> who do you think set up the studies and why <pause dur="2.1"/> lady there <kinesic desc="indicates member of audience" iterated="n"/> the in the black jumper <pause dur="0.3"/> who do you think </u><pause dur="0.4"/> <u who="sf0493" trans="pause"> # </u><pause dur="0.4"/> <u who="nm0454" trans="pause"> would an old cynic like me set up a study </u><pause dur="1.5"/> <u who="sf0493" trans="pause"> # </u><u who="nm0454" trans="latching"> who would set up such a study and why </u><pause dur="0.8"/> <u who="sf0493" trans="pause"> i guess people that <pause dur="0.3"/> <unclear>can</unclear> # <pause dur="0.3"/> didn't believe that # <pause dur="0.7"/> it had a difference </u><pause dur="0.5"/> <u who="nm0454" trans="pause"> so either the <pause dur="0.2"/> the the knockers <pause dur="0.3"/> like me <pause dur="0.5"/> or more likely </u><pause dur="0.6"/> <u who="sf0493" trans="pause"> people trying to prove it </u><pause dur="0.2"/> <u who="nm0454" trans="pause"> the believers </u><u who="sf0493" trans="overlap"> yeah </u><u who="nm0454" trans="overlap"> and who are the believers </u><pause dur="0.2"/> <u who="sf0494" trans="pause"> drug companies </u><pause dur="0.8"/> <u who="sm0495" trans="pause">

pharmaceutical companies </u><u who="nm0454" trans="overlap"> pharmaceutical companies yeah ah there's a cynic <pause dur="0.3"/> that's what i like to hear <pause dur="0.8"/> <vocal desc="laughter" iterated="y" n="ss" dur="1"/> excellent i know i know where to get the cynical pharmaceutical companies yeah <pause dur="0.6"/> diabetologists <pause dur="0.4"/> it's their raison d'être <pause dur="0.4"/> you know <pause dur="0.2"/> if tight diabetic control doesn't lead to good outcomes what's the point of a diabetologist don't tell other people <pause dur="0.3"/> don't tell <pause dur="0.4"/> all these professors Professor <gap reason="inaudible" extent="1 sec"/> and everybody <pause dur="0.4"/> don't tell them don't even mention my name i didn't exist <pause dur="0.4"/> don't <trunc>exi</trunc> i wasn't here <pause dur="0.3"/> but you know it's their raison d'être <pause dur="0.2"/> and it may not be true <pause dur="0.9"/> now you can <trunc>s</trunc> you can be just as cynical about kidney medicine as well renal units well i've come back from Australia drop it in the conversation <pause dur="0.2"/><vocal desc="laughter" iterated="y" n="ss" dur="1"/> i visted a a renal unit in in north-west Australian <pause dur="0.3"/> there were no nephrologists there they don't need one <pause dur="0.2"/> they worked it out themselves <pause dur="0.2"/> and a forty-bedded <pause dur="0.2"/>

dialysis is run by nurses and G-Ps so you know <pause dur="0.4"/> do we need nephrologists maybe not <pause dur="0.7"/> and it's quite interesting actually slight aside i i asked one of the G-Ps <pause dur="0.3"/> # <pause dur="0.2"/> <trunc>h</trunc> how how she knows so much about # <pause dur="0.6"/> # dialysis and kidney transplantation <pause dur="0.3"/> she said <shift feature="voice" new="mimicking Australian accent"/>well mate i've got a bit of paper <shift feature="voice" new="normal"/> <pause dur="1.1"/> and <shift feature="voice" new="laugh"/>she showed <shift feature="voice" new="normal"/>it's absolutely brilliant she showed so we had a bit of paper on the wall <pause dur="0.4"/> and the whole of nephrology was <pause dur="0.3"/> # summarized on one single bit of paper and it was absolutely brilliant you know <pause dur="0.2"/> creatinine goes up put them on the whirly they've got oedema put them on the whirly <pause dur="0.3"/> diabetes it's probably diabetic nephropathy put them on the whirly <pause dur="0.5"/> and <pause dur="0.3"/> <vocal desc="laughter" iterated="y" n="ss" dur="2"/> # <pause dur="0.3"/> and it was all there one bit of paper <pause dur="0.6"/> and i thought <shift feature="voice" new="mimicking an angry voice"/> my whole specialty <vocal desc="laughter" iterated="y" n="ss" dur="1"/>on one bit of paper this is terrible <shift feature="voice" new="normal"/> <pause dur="0.6"/> # but the same

can be said of of of of most specialties you know what is the the point of us <pause dur="0.3"/> # i don't know <pause dur="0.2"/> that's not for for for me to judge <pause dur="0.8"/> okay <pause dur="0.5"/> # <pause dur="1.8"/> treatment <pause dur="0.2"/> treatment so we talked about some treatments that # might work <pause dur="0.4"/> could work should work <pause dur="0.3"/> in fact <gap reason="inaudible" extent="1 sec"/><pause dur="0.5"/> let's <pause dur="0.2"/> be a bit less cynical <pause dur="0.8"/> and think about what we can do <pause dur="1.3"/> well we can only do what we can do we can only do what what what <pause dur="0.4"/> powers are given to us what drugs are given to us <pause dur="0.5"/> and the important <pause dur="0.2"/> thing in <trunc>diabe</trunc> diabetic nephropathy is to rationalize the problems <pause dur="0.4"/> to rationalize the problems in an early stage and attempt to do something about it <pause dur="0.2"/> even if it's all claptrap <pause dur="0.3"/> at least it gives the patient something to do <pause dur="1.1"/> the sort of things you can do <pause dur="0.2"/> you can achieve <pause dur="0.2"/> tight diabetic control that's what the D-C-C-T and U-K-P-D-S <pause dur="0.2"/> that's what i think they really showed <pause dur="0.3"/> they showed it was possible and nobody had ever shown it was possible <pause dur="0.9"/> tight diabetic control as shown by H-B-A-one-C <pause dur="0.6"/> you can get the blood pressure down <pause dur="0.3"/>

you can favour ACE inhibitors and <unclear>ACE</unclear> antagonists <pause dur="0.2"/> these things do work <pause dur="0.2"/> they do affect <pause dur="0.2"/> soft end points <pause dur="0.9"/> at the later stages if you have people with advanced <pause dur="0.7"/> complicated diabetes diabetic retinopathy <pause dur="0.5"/> it's going to get a bit <unclear>vague</unclear> <pause dur="0.2"/> <unclear>later</unclear> <pause dur="0.7"/> diabetic nephropathy <pause dur="1.0"/> prepare them for dialysis <pause dur="0.7"/> diabetic legs <pause dur="0.8"/> not much you can do <pause dur="0.3"/> send them to Mr <gap reason="name" extent="1 word"/> <pause dur="0.4"/> # <pause dur="0.3"/> but <pause dur="0.5"/> there are things we can do at these earlier stages and <trunc>wi</trunc> to those of you who are going to be G-Ps it's very important to recognize these early stages and do something about them <pause dur="0.5"/> don't be a cynical Dr <gap reason="name" extent="1 word"/> don't wait till their legs fall off go blind <gap reason="inaudible" extent="1 sec"/> <pause dur="0.4"/> try to prevent that stage if you can <pause dur="1.8"/> okay <pause dur="0.2"/> so i don't particularly want to talk about the the treatment <pause dur="0.3"/> of end-stage renal failure which is the final stage of diabetic nephropathy in any great detail today <pause dur="0.3"/> other than to say that it exists <pause dur="0.4"/> the treatment's for them really the same as for <pause dur="0.2"/> non-diabetic diseases <pause dur="0.3"/> dialysis peritoneal dialysis haemodialysis

transplantation <pause dur="1.2"/> kidney alone transplants <pause dur="0.4"/> what i would like to leave you with is some thoughts for the future <pause dur="0.3"/> in terms of the treatment of of diabetic nephropathy <pause dur="0.3"/> until <pause dur="0.8"/> <gap reason="name" extent="1 word"/> can crack it and we can sort out the the how and the why question <pause dur="0.3"/> we have to go back to a bit of our old agricultural medicine <pause dur="0.7"/> which is <pause dur="0.2"/> chopping things out of other people <pause dur="0.4"/> and putting them into other people <pause dur="0.6"/> and <pause dur="0.3"/> the modern treatment for diabetic nephropathy in an IDDM <pause dur="0.4"/> <trunc>wh</trunc> <trunc>wh</trunc> <kinesic desc="indicates member of audience" iterated="n"/> why would it not work in a NIDDM <pause dur="0.4"/> it's a kidney pancreas transplant why would that not work in a NIDDM </u><pause dur="1.2"/> <u who="sf0496" trans="pause"> because the tissues will have been </u><pause dur="1.1"/> <u who="nm0454" trans="pause"> what's </u><u who="sf0496" trans="overlap"> <gap reason="inaudible" extent="1 sec"/> </u><u who="nm0454" trans="overlap"> what's the difference between IDDM and NIDDM in terms of <pause dur="0.6"/> the the the the the the the underlying problem <pause dur="0.5"/> <event desc="noise from audience" iterated="y" dur="1"/> shush listen </u><pause dur="0.4"/> <u who="sf0497" trans="pause"> 'cause in a NIDDM it's more of the tissues being non-receptive <gap reason="inaudible" extent="1 sec"/> </u><u who="nm0454" trans="overlap"> very good okay so in <pause dur="0.4"/> IDDM you don't make it in NIDDM you can't respond to it <pause dur="0.3"/> and

therefore if you put a new kidney pancreas into somebody it won't it work won't make any difference they won't respond to it <pause dur="1.3"/> and <pause dur="0.2"/> it can sometimes <pause dur="0.2"/> be quite difficult to tell the difference between IDDM and NIDDM because <pause dur="0.4"/> younger people are getting fatter linear bias again the things aren't as good as they used to be <pause dur="0.3"/> but you know <pause dur="0.4"/> people are getting <shift feature="voice" new="laugh"/>fatter actually <shift feature="voice" new="normal"/><pause dur="0.2"/> and # and # even even if you chuck out linear bias <pause dur="0.3"/> and with it diabetes is getting more complicated <pause dur="0.2"/> so we now see people in their thirties fat people <pause dur="0.3"/> with diabetes and it's sometimes quite difficult to tell whether they're <pause dur="0.3"/> a new IDDM <pause dur="0.3"/> # <pause dur="0.3"/> or an insulin-requiring NIDDM <pause dur="0.5"/> # you can measure <pause dur="0.3"/> what can you measure <pause dur="1.1"/> one <pause dur="2.2"/> biochemical test which is useful </u><pause dur="0.2"/> <u who="sm0498" trans="pause"> <gap reason="inaudible" extent="1 sec"/> insulin </u><pause dur="0.3"/> <u who="nm0454" trans="pause"> yes C-peptides are quite good at at # differentiate them so we don't normally do it because usually <pause dur="0.3"/> # it it is it is clinically obvious <pause dur="1.1"/> so the problem with combined kidney pancreas

transplantation <pause dur="0.3"/> is <pause dur="0.4"/> it's only good for a few fit usually white IDDMs <pause dur="0.2"/> so it isn't <pause dur="0.5"/> the saviour of the free world it isn't the saviour <pause dur="0.2"/> <trunc>o</trunc> of diabetes <pause dur="0.3"/> and in Coventry i've established a link with Guy's which is one of the units in the U-K which <pause dur="0.3"/> does kidney pancreases <pause dur="0.3"/> and we have <pause dur="0.2"/> # a couple of patients on their waiting list and one has <pause dur="0.3"/> has # received a kidney pancreas transplant <pause dur="0.4"/> # <pause dur="0.3"/> about six months ago and she now has <pause dur="0.5"/> a normal blood sugar <pause dur="0.2"/> and normal kidney function <pause dur="0.4"/> hoorah <pause dur="0.6"/> # her hair's falling out due to tacrolimus <pause dur="0.3"/> her face is fat <pause dur="0.3"/> due to prednisolone <pause dur="0.4"/> and she was beautiful <pause dur="0.3"/> and now she isn't but she's got normal kidney function <pause dur="0.3"/> and # she doesn't have diabetes <pause dur="0.5"/> she's also oh yeah she's had to spend six <pause dur="0.2"/> months living in London <pause dur="0.3"/> which she didn't want to do <pause dur="0.4"/> but # <pause dur="0.6"/> the the it is possible <pause dur="0.2"/> # they are being done not in any great numbers i mean Guy's last year did about twelve and you know they're covering a lot of the <pause dur="0.2"/> a lot of the United Kingdom so <pause dur="0.3"/> in statistical

terms it's <pause dur="0.2"/> as important <pause dur="0.4"/> # or less important than a heart transplant about two-hundred heart transplants done in the U-K every year <pause dur="1.4"/> # <pause dur="0.3"/> so what about the future future # pancreatic islet transplantation has been tried in the U-K before <pause dur="0.3"/> # <pause dur="0.3"/> didn't really work i was in <gap reason="inaudible" extent="1 sec"/> in the early nineties and we tried it and it all went horribly wrong <pause dur="0.6"/> # <pause dur="0.3"/> so we we aborted a programme quite early <pause dur="0.3"/> # <trunc>s</trunc> there's a group in Canada who's come up with a new protocol <pause dur="0.2"/> and # various units in the U-K are starting to copy that now <pause dur="0.2"/> and the idea is you graft pancreatic islet cells in the laboratory <pause dur="0.3"/> and <pause dur="0.2"/> inject them into where does anybody know where we inject them into </u><pause dur="0.2"/> <u who="sm0499" trans="pause"> liver </u><u who="nm0454" trans="latching"> into the liver <pause dur="0.2"/> and # <pause dur="0.3"/> they spread through the liver and other organs and form little <pause dur="0.3"/> # pancreases little islets of of Langerhans <pause dur="0.6"/> # <pause dur="0.8"/> so <pause dur="0.2"/> that may be the future of stem cell research <pause dur="0.3"/> there

are some <pause dur="0.2"/> advances in the near future which i think will come through things like inhaled insulin <gap reason="inaudible" extent="1 sec"/> <pause dur="0.6"/> # <pause dur="0.3"/> but there are some small things <pause dur="0.2"/> which which are coming through <pause dur="0.3"/> i don't personally feel that we're going to <pause dur="0.2"/> # <pause dur="0.2"/> be treating diabetes much better than Banting and Best <pause dur="0.4"/> until <pause dur="0.2"/> somebody clever <vocal desc="laugh" iterated="n"/> <pause dur="0.5"/> like <gap reason="name" extent="1 word"/> <pause dur="0.3"/> # <pause dur="0.2"/> actually cracks the the how and the why question <pause dur="0.2"/> i think our our treatments are still # agricultural <pause dur="0.9"/> okay that's it on diabetes have a <pause dur="0.3"/> ten <pause dur="0.6"/> minute break before you go any questions on diabetes and then <trunc>w</trunc> when you come back it'll be glomerular disease <pause dur="0.6"/> any questions diabetes </u><pause dur="0.2"/> <u who="sm0499" trans="pause"> yes </u><u who="nm0454" trans="latching"> diabetic nephropathy <pause dur="1.3"/> if you're shy come down the front <gap reason="inaudible" extent="1 sec"/> okay </u><gap reason="break in recording" extent="uncertain"/> <u who="sf0470" trans="pause"> # i just want to know like why would you give insulin to a type two <trunc>diabet</trunc> diabetic patient </u><u who="nm0454" trans="overlap"> do you know i i i thought that when i was a student i couldn't <shift feature="voice" new="laugh"/>work it out <shift feature="voice" new="normal"/></u><u who="sf0470" trans="overlap"> i don't understand it </u><u who="nm0454" trans="overlap"> why you'd give insulin </u><u who="sf0470" trans="overlap"> i don't see how <gap reason="inaudible" extent="2 secs"/></u><u who="nm0454" trans="overlap">

why you'd give insulin no <trunc>wh</trunc> why would <pause dur="0.6"/> # <pause dur="0.2"/> i suppose because <pause dur="0.6"/> somebody tried it once and it worked <pause dur="0.3"/> i mean conventionally NIDDMs we start off <pause dur="0.4"/> on agents such as sulphonylureas as you know <pause dur="0.2"/> biguanides <pause dur="0.3"/> there's this new group called the glitazones we're using acarbose <pause dur="0.5"/> but <pause dur="0.3"/> it seems to me that the <pause dur="0.3"/> that the the pancreas sort of gets worn out <pause dur="0.3"/> and you you you keep stimulating it you know <pause dur="0.4"/> # <pause dur="0.3"/> some of the drugs work by stimulating the pancreas some <pause dur="0.3"/> by # # reducing the <pause dur="0.4"/> insensitivity to insulin <pause dur="0.6"/> but eventually it seems to <pause dur="0.2"/> you know you you're you're bashing away at the pancreas and then it <pause dur="0.5"/> wears out then we don't have anything else to do 'cause the blood sugar's still rising <pause dur="0.5"/> <trunc>a</trunc> and and so a somebody somewhere along the line <pause dur="0.4"/> tried insulin but you're right it shouldn't work really <pause dur="0.3"/> all i <trunc>c</trunc> </u><u who="sf0470" trans="overlap"> but typically you do </u><u who="nm0454" trans="overlap"> yeah </u><u who="sf0470" trans="overlap"> you do do that </u><u who="nm0454" trans="overlap"> i mean i all i can think of is it's some supersaturated system <pause dur="0.5"/> and if you you know give

enough <pause dur="0.5"/> i mean some NIDDMs need large doses <pause dur="0.5"/> # </u><u who="sf0470" trans="latching"> yes </u><u who="nm0454" trans="overlap"> that that that it you can break through the lack of responsiveness to <pause dur="1.0"/> it's not a very good answer </u><u who="sf0470" trans="overlap"> but you still do that practically you do do that <gap reason="inaudible" extent="1 sec"/> </u><u who="nm0454" trans="overlap"> yeah practically <pause dur="0.3"/> so you know <pause dur="0.2"/> if you achieve good diabetic control and by that i mean a an H-B-A-one-C of less than eight say <pause dur="0.4"/> and you know <pause dur="0.5"/> # most blood sugars <pause dur="0.3"/> you know <pause dur="0.3"/> in the normal range or just above the normal range <pause dur="0.4"/> with tablets then that would be fine <pause dur="0.8"/> # if you didn't <pause dur="0.2"/> few patients are just controlled by diet alone <pause dur="0.3"/> if you didn't you'd add insulin </u><pause dur="0.3"/> <u who="sf0470" trans="pause"> yeah </u><pause dur="0.4"/> <u who="nm0454" trans="pause"> and <pause dur="0.2"/> 'cause quite a few patients are on both actually </u><pause dur="0.4"/> <u who="sf0470" trans="pause"> yeah </u><gap reason="break in recording" extent="uncertain"/> <u who="nm0454" trans="pause"> we just don't know i mean you know we can say that if you you know you do biopsies you

see this thickening of the glomerular basement membrane you see <pause dur="0.4"/> # <pause dur="0.5"/> proliferation in the mesangium <pause dur="0.4"/> but you know <pause dur="0.3"/> but <pause dur="0.3"/> but <pause dur="0.6"/> what leads to that and why that leads to <pause dur="0.5"/> # <pause dur="0.2"/> proteinuria <pause dur="0.7"/> we don't know <pause dur="0.3"/> i mean i'm going to talk about it a bit in the second talk about <pause dur="0.2"/> there are some various theories about <pause dur="0.4"/> why <pause dur="0.4"/> # <pause dur="0.3"/> proteinuric diseases <pause dur="0.3"/> happen <pause dur="0.6"/> # <pause dur="0.3"/> well it isn't obvious is it really <pause dur="0.7"/> you know </u><pause dur="0.4"/> <u who="sm0500" trans="pause"> <gap reason="inaudible" extent="1 sec"/> it's all about glycosylation of the basement </u><pause dur="0.8"/> <u who="nm0454" trans="pause"> yeah </u><u who="sm0500" trans="overlap"> <gap reason="inaudible due to overlap" extent="1 sec"/> </u><u who="nm0454" trans="overlap"> i mean you you you <pause dur="0.4"/> you you may know more about it than than i do but i i i <pause dur="0.4"/> # <pause dur="0.2"/> i <pause dur="0.8"/> # and you know chip in in the second talk <pause dur="0.3"/> i don't think we know but <pause dur="0.3"/> all you can say is that <pause dur="0.5"/> a high blood sugar does seem to be associated <pause dur="0.4"/> reason we don't understand <pause dur="0.5"/> with proteinuria <pause dur="0.7"/> and and and that <pause dur="0.3"/> eventually if untreated leads to renal failure </u><pause dur="1.3"/> <u who="nf0473" trans="pause"> <gap reason="inaudible" extent="1 sec"/> the photocopier's broken so i think that's <gap reason="inaudible" extent="1 sec"/> </u><u who="nm0454" trans="overlap"> okay </u><u who="nf0473" trans="overlap">

so i'll come back <pause dur="0.3"/> when i've done them so </u><u who="nm0454" trans="latching"> okay right </u><u who="nf0473" trans="overlap"> we'll do them </u><pause dur="0.4"/> <u who="sm0500" trans="pause"> so </u><u who="nm0454" trans="overlap"> right so </u><u who="sm0500" trans="overlap"> you could just say <gap reason="inaudible" extent="1 sec"/></u><pause dur="0.5"/> <u who="nm0454" trans="pause"> in simple terms i mean what i tell a patient what i <trunc>m</trunc> is is is that <pause dur="0.3"/> that <trunc>i</trunc> is is the high blood sugar somehow damages <pause dur="0.4"/> # and i i draw them diagrams <trunc>o</trunc> <trunc>o</trunc> of glomeruli and things and <pause dur="0.3"/> and if they the more articulate patient i i i would actually <pause dur="0.4"/> i think in one of my previous talks i talked about the kidney being a tube <pause dur="0.3"/> i'll i'll talk about that in in in the second in my second talk <pause dur="0.2"/> you know and i'd actually do like draw glomeruli and and draw <pause dur="0.3"/> # the the capillary the the the <pause dur="0.4"/> intraglomerular capillary <pause dur="0.4"/> and say somehow the blood sugar damages the wall <pause dur="0.3"/> and makes sort of <pause dur="0.2"/> holes in the wall <pause dur="0.3"/> and protein <pause dur="0.3"/> which normally passes through the kidney then falls out you know i <trunc>wi</trunc> <pause dur="0.3"/> i'll talk about a bit in that second talk <pause dur="0.5"/> # <pause dur="0.5"/> but somehow <pause dur="0.4"/> you know <pause dur="0.5"/> the high blood sugar

somehow leads to proteinuria and that eventually </u><u who="sm0501" trans="overlap"> <gap reason="inaudible" extent="1 sec"/></u><u who="nm0454" trans="latching"> yeah that's going to be <pause dur="0.3"/> # </u><u who="sm0501" trans="overlap"> <gap reason="inaudible" extent="2 secs"/></u><u who="nm0454" trans="latching"> # <pause dur="0.4"/> <event desc="passes handout to audience member" iterated="n"/> that's the spare one that's yours yeah okay <pause dur="1.6"/> i've not really answered your question but <vocal desc="laughter" iterated="y" n="sf0502" dur="1"/> it's it's because we don't it's 'cause we don't know </u><u who="sf0502" trans="overlap"> do you get a decreased G-F-R <pause dur="0.4"/> does it <gap reason="inaudible" extent="1 sec"/> </u><u who="nm0454" trans="overlap"> eventually yeah that's the stage <trunc>f</trunc> oh it's on the previous <trunc>as</trunc> that's the stage four <pause dur="0.3"/> it's when the G-F-R goes down and then your creatinine starts to rise </u><u who="sf0502" trans="latching"> so first it affects <pause dur="0.2"/> the <pause dur="0.5"/> # <pause dur="0.2"/> the nephron and then it affects <pause dur="0.4"/> the vessels </u><pause dur="0.4"/> <u who="nm0454" trans="pause"> well it it it affects really <pause dur="0.3"/> diabetes affects the large vessels <pause dur="0.2"/> in simple old old <pause dur="0.4"/> bog standard atheroma </u><pause dur="0.3"/> <u who="sf0502" trans="pause"> yeah </u><u who="nm0454" trans="latching"> and the small vessels in this other way which we don't understand </u><pause dur="0.4"/> <u who="sf0502" trans="pause"> oh yeah </u><u who="nm0454" trans="overlap"> and and and both lead to the renal impairment <pause dur="1.5"/> traditionally you're not told <pause dur="0.3"/> that

renovascular disease is part of diabetic nephropathy </u><pause dur="0.3"/> <u who="sf0502" trans="pause"> mm-hmm </u><u who="nm0454" trans="latching"> but i think it must be i don't because you can't <pause dur="0.2"/> define the size <pause dur="0.4"/> of a blood vessel <pause dur="0.2"/> you know the big ones the small one <kinesic desc="indicates member of audience" iterated="n"/> </u><pause dur="0.6"/> <u who="sm0503" trans="pause"> yeah </u><u who="nm0454" trans="overlap"> do you want to ask a question or </u><u who="sm0503" trans="latching"> <unclear>i've actually</unclear> <pause dur="0.7"/> i think first of all <pause dur="0.5"/> do you know who actually published # <gap reason="inaudible" extent="2 secs"/> </u><u who="nm0454" trans="latching"> # no the i think they were both published without authors </u><pause dur="0.2"/> <u who="sm0503" trans="pause"> right </u><pause dur="0.2"/> <u who="nm0454" trans="pause"> so # and and so if you look up D-C-C-T on the Internet you get <trunc>hun</trunc> thousands of of of of # papers <pause dur="0.4"/> i think it was nineteen-ninety-one New England Journal <pause dur="0.6"/> and the the the <pause dur="0.2"/> nineteen-ninety-one i think or could be three <pause dur="0.4"/> # the the the # <pause dur="0.6"/> U-K-P-D-S was about nineteen-ninety-nine and two-thousand <pause dur="0.5"/> and that was published in several stages <pause dur="1.2"/> # and it and then <pause dur="0.5"/> you know i mean i know i'm cynical about it but it it is <pause dur="0.2"/> the best information we've got <pause dur="0.5"/> and # <pause dur="0.7"/> which is # <pause dur="0.2"/> why we <pause dur="0.3"/> and # when i'm even

though i'm cynical with you lot i'm not <pause dur="0.5"/> completely cynical with patients because if you <pause dur="0.2"/> if you give them my old <pause dur="0.2"/> linear bias spiel and <pause dur="0.3"/> and <pause dur="0.2"/> Judaeo-Christian <pause dur="0.5"/> model of controlling the world <pause dur="0.3"/> you know that <pause dur="0.2"/> basically removes all hope <pause dur="0.4"/> from the patient </u><pause dur="0.4"/> <u who="sm0501" trans="pause"> yeah </u><u who="nm0454" trans="latching"> and that i wouldn't recommend you know because <pause dur="0.3"/> you mustn't ever remove hope from a patient <pause dur="0.4"/> 'cause their only hope is that you <pause dur="0.4"/> either get rid of their diabetes or or or or at least you control it <gap reason="ethics" extent="4 mins 22 secs"/>