(link). He probably is going to say something stupid. According to a new paper: The Mere Anticipation of an Interaction with a Woman Can Impair Men’s Cognitive Performance. ‘Further studies needed’ etc., but I’m inclined to believe that they are right and that yes, males are actually that stupid and impressionable. Though effect sizes are important to have in mind too.
ii. I thought this was funny. Then again I’m weird.
iii. I’ve added Guam to my list of ‘places I don’t want to visit anytime in the near future’. Why? Because of this.
“Birds are dominant apex predators in terrestrial systems around the world, yet all studies on their role as predators have come from small-scale experiments; the top-down impact of bird loss on their arthropod prey has yet to be examined at a landscape scale. Here, we use a unique natural experiment, the extirpation of insectivorous birds from nearly all forests on the island of Guam by the invasive brown tree snake, to produce the first assessment of the impacts of bird loss on their prey. We focused on spiders because experimental studies showed a consistent top-down effect of birds on spiders. We conducted spider web surveys in native forest on Guam and three nearby islands with healthy bird populations. Spider web densities on the island of Guam were 40 times greater than densities on islands with birds during the wet season, and 2.3 times greater during the dry season. These results confirm the general trend from manipulative experiments conducted in other systems however, the effect size was much greater in this natural experiment than in most manipulative experiments. [...]
We compared the abundance of web-building spiders on Guam to that on Rota, Tinian and Saipan. At each site, we set up 1–3 transects, separated by at least 200 meters. The transects were 20 or 30 meters long, depending on the year. We counted all visible webs within 1 horizontal meter of each transect centerline and up to 2 vertical meters above the ground. Webs lacking a spider were considered abandoned, and not counted. [...] Guam, without birds, had a mean of 18.37 spider webs per ten meters in the wet season, compared to 0.45 webs per ten meters on nearby islands with birds [...]. In the dry season, Guam had 26.19 spider webs per ten meters compared to 11.37 webs per ten meters on nearby islands with birds”
iv. You Don’t Know Me, But I Know You: The Illusion of Asymmetric Insight, by Pronin, Kruger, Savitsky and Ross. Interesting. The abstract:
“People, it is hypothesized, show an asymmetry in assessing their own interpersonal and intrapersonal knowledge relative to that of their peers. Six studies suggested that people perceive their knowledge of their peers to surpass their peers’ knowledge of them. Several of the studies explored sources of this perceived asymmetry, especially the conviction that while observable behaviors (e.g., interpersonal revelations or idiosyncratic word completions) are more revealing of others than self, private thoughts and feelings are more revealing of self than others. Study 2 also found that college roommates believe they know themselves better than their peers know themselves. Study 6 showed that group members display a similar bias—they believe their groups know and understand relevant out-groups better than vice versa. The relevance of such illusions of asymmetric insight for interpersonal interaction and our understanding of “naive realism” is discussed.”
v. Crunching the data on human brain evolution. Which functional form fits the underlying process better is an interesting discussion but I’d like to note that what I first thought when seeing these (or rather, similar depictions elsewhere) was: ‘hey, look at that standard deviation!’
vi. Social rejection shares somatosensory representations with physical pain. Another fMRI-study. I don’t know enough about this stuff to comment on the validity of the conclusions, but I’ll probably bookmark it and keep it for later so that I’ll be able to use it to justify my decision not to ask out the hypothetical cute girl in class next semester (or whatever).
vii. Quality of Diabetes Care in Italy. I’m glad I don’t live in Italy:
“Of 126,163 diabetic individuals (prevalence of diabetes 5.8%, mean age 71 years), as many as 42% did not have their HbA1c measured for over a year. Even considering only insulin-treated people, this frequency remains disappointingly high (35%). The proportion of people having at least two annual tests for HbA1c was low (32.7%; 43.1% among insulin-treated patients). [...] Another disappointing finding is the very low proportion of subjects in whom microalbuminuria was tested (27%) in spite of its role as a strong predictor of cardiovascular diseases and dialysis. Annual testing for plasma total cholesterol (61.2%), creatinine (58.9%), eye examination (11.1%), electrocardiogram (25.1%), and arterial echo-Doppler (15.9%) were low.”
I recently posted some corresponding Danish numbers here, though unfortunately that post is in Danish. In Denmark approximately 95% of diabetics get their HbA1c measured at least once a year. I get my HbA1c tested 3-4 times a year and I’d have no clue what to do without these numbers. 92% of Danish patients cared for by the hospital outpatient clinics (diabetesambulatorier) and 55% of the patients treated by their local GP were tested for microalbuminuria at least once every two years. I’m tested once per year. I frankly found it shocking that the Italic HbA1c numbers were that low but I probably should have known better, given the variation in diabetes care across countries. Not all of the variables mentioned are equally important but Italy fails at the really basic stuff too. For a Danish diabetic to move to a place like (Southern) Italy (I’m almost certain the situation is far worse in the south than in the north) would be a bit like an old and frail person moving to a place where they haven’t heard about penicillin. This stuff is a big part of why I’m not very likely to move away from Denmark when I finish my education – a lot of places I basically consider ‘off limits’ because I’d be gambling with my health by moving there, and even a lot of relatively advanced societies still have diabetes treatment protocols which belong in the (metaphorical) Stone Age.
(To regular readers who don’t speak/read Danish: When I started out writing this post I fully intended to post it in English – but I found out along the way that it just didn’t make sense to try to do that as all the source material is in Danish. However this Danish post is a one-time thing. If you do not completely understand what’s going on in the post but you’re nevertheless curious about some stuff covered here, just ask. With all that out of the way:)
Tallene i posten er alle fra Det National Indikatorprojekt (NIP)’s 2011-rapport om diabetes som du kan se her. Klik på dem for at se tabellerne i fuld størrelse. Først, BMI:
Median-BMI for type 1 diabetikere i ovenstående sample, som dækker patienter i behandling på diabetesambulatorierne, er 25,1 – hvilket sandsynligvis er på niveau med median-BMI for befolkningen som helhed (se side 63 her). Derimod er median-BMI for type 2 diabetikere 30,8. Det er bemærkelsesværdigt at hele fordelingen for type to patienternes vedkommende synes at være forskubbet mod højre – bemærk at 10%-fraktilen for type 2′ere for alle regioners vedkommende er over 24 – overvægt og fedme er en meget vigtig variabel for udviklingen af type 2 diabetes, og relativt få type 2 diabetikere er ikke overvægtige eller fede.
Hvad med rygning?
Mere end halvdelen af type 1′ere har aldrig røget, mens tallet er lavere for type 2′erne, der så til gengæld har flere eksrygere. Generelt synes patientgruppernes andel af individer der ryger dagligt groft at matche befolkningens som helhed – 20-25% ryger dagligt.
En indikator for behandlingskvalitet (der er mange af disse i rapporten): Kommer diabetikere med forhøjet blodtryk i behandling?
Mere end hver tredje type 1 patient på landsplan med forhøjet blodtryk som er i ambulant behandling og næsten hver anden type 1 patient med forhøjet blodtryk som bor i hovedstadsområdet behandles ikke for det forhøjede blodtryk. Tallene er langt bedre for type 2′erne. Bemærk dog også at det trods alt går i den rigtige retning i København. For patienter behandlet i almen praksis var tallene for blot få år siden voldsomt høje, men ligner nu ambulatoriernes:
Men hvor mange har hypertension?
Hver fjerde patient har et systolisk tryk over 140.
Øjenundersøgelser? De er væsentlige fordi diabetikere som ikke får foretaget øjenundersøgelser kan risikere at miste deres syn, og de er væsentlige fordi det lader til, et forhold rapporten også kritiserer stærkt, at ingen reelt har styr på, hvordan det står til pga. mangelfuld registrering og rapportering fra de implicerede parter. Rigtigt mange af patienterne i behandling i privat praksis lader ikke til at deltage i øjenscreeningerne, hvilket dog kan være et resultat af manglende rapportering. Ingen ved det med sikkerhed. Tallene:
At dømme ud fra disse tal får mere end hver anden diabetiker behandlet i almen praksis ikke undersøgt deres øjne regelmæssigt som anbefalet. Det er stærkt tvivlsomt at det forholder sig sådan, men hvordan det så i stedet forholder sig er ikke til at sige.
Næste variabel: Hba1c, eller glykeret hæmoglobin. Et almindeligt blodsukker målt med et blodsukkerapparat angiver blodsukkeret på prøvetidspunktet. Det er nyttigt i behandlingsregi, men sådan et blodsukker fortæller ikke så meget om hvordan blodsukkeret generelt opfører sig på langt sigt – for at vide det skal der bruges mange målinger. Eller man kan bruge Hba1c – det gode ved glykeret hæmoglobin er at variablen kan bruges til at estimere hvad ‘gennemsnitsblodsukkeret’ har været over et langt tidsrum, et par måneder eller tre. Variablen er en meget stærk indikator for hvor godt en diabetiker er reguleret, selvom den dog ikke kan stå alene. Nogle tal:
Over 20% af patienterne når ikke målet om en Hba1c på under 9 (DCCT (%))/75 (IFCC mmol/mol) [link]. Det er i den sammenhæng, interessant, at ‘officielle behandlingsmål’ for patienter er enten < 6,5 % eller <7,0%, afhængig af hvem man spørger (se linket). De fleste patienter kommer aldrig i nærheden af sådanne værdier, afstanden mellem 9,0% og 7,0% er enorm. Som omtalt på twitter var min sidste Hba1c 7,1%. For bare få år siden ville det have været vel inden for behandlingsmålene, og givet hvor lang tid jeg har haft sygdommen og hvor store problemer jeg har haft med hypoglykæmi vil jeg næppe gå efter at sænke den ret meget yderligere. Tallene for type 2 patienter er ikke meget anderledes, omend de generelt er lidt højere – gennemsnittet er 82% (81-82) som opfylder målet. Tallene er bedst for patienter behandlet i almen praksis, hvilket jeg fandt overraskende. Her er lidt flere tal med supplerende information om fordelingen af værdier:
Så at dømme ud fra disse data og målt alene på baggrund af Hba1c tilhører jeg den bedst regulerede fjerdedel af type 1 diabetikere i ambulant behandling. Det er sandsynligvis under 20% af patienterne som når det nuværende behandlingsmål på 7,0%. Og under 10% af patienterne opfylder det på nuværende tidspunkt anbefalede behandlingsmål fra EFSD (6,5%).
Hvor længe har diabetikere i behandling haft deres sygdom? Det varierer meget, men her er tallene:
Her findes formentligt en af årsagerne til, at type 2 patienter behandlet i almen praksis i højere grad opfylder Hba1c behandlingsmålet; de har haft sygdommen i færre år end patienterne behandlet på ambulatorierne. Det er selvfølgelig spekulation fra min side, men det synes ikke usandsynligt at praktiserende læger primært håndterer ukomplicerede tilfælde, hvorefter ambulatorier så tager over når komplikationer støder til. Patienter med komplikationer har højere Hba1c end patienter uden, og compliance er som regel et større problem. Hvis disse overvejelser er korrekte giver det nogle problemer i forhold til at sammenligne Hba1c-resultaterne opnået blandt patienter behandlet ambulant og patienter behandlet i almen praksis.
Tilbage til varigheden. Jeg er mest interesseret i type 1. Bemærk her at varigheden også på sin vis er en indikator for levetid, fordi ingen patienter forlader behandlingssystemet og stopper med at være syge: Du stopper med at være i behandling for din sygdom når du er død eller når du er hjemløs, hvad der end kommer først (
ingen addresse -> intet sygesikringskort og ingen tilknyttet læge (se kommentar). Men ingen læge -> ingen insulin, ingen insulin -> død. Helt så slemt er det ikke for alle T2′ere, selvom 67% af dem også tager insulin – se side 95). På den måde er det sigende at kun 10% af type 1 diabetikere på landsplan har haft sygdommen i mere end ~42 år. På den anden side ved jeg ikke helt hvor meget man kan konkludere mht. dødelighed på baggrund af disse data, der kan også være sampling-aspekter eller data-format faktorer der spiller ind, som jeg ikke er opmærksom på. Der findes heller ingen tabel som angiver alder på diagnosetidspunktet for den pågældende sample, og den variabel er naturligvis meget væsentlig i denne sammenhæng, ligesom den forklarer den gennemsnitligt langt kortere varighed for type 2 patienter. Dertil kommer at variablen mest relaterer til dødeligheden ud fra et historisk perspektiv, snarere end ud fra et nutidigt perspektiv – og diabetes var langt mere dødelig for 50 år siden end sygdommen er i dag.
Posten her indeholder kun et lille udsnit af de mange data som rapportens 114 sider indeholder. Hvis du er nysgerrig så kan jeg kun anbefale dig at læse videre her.
I’ve touched upon how a large number of more or less external factors impact the formation of the political opinions of people before, and as political opinions (and religious views) are huge drivers of behaviour more generally, naturally we should also expect such variables to impact ‘personality’ more broadly. Young males are less risk averse than young females and older males. Where you are born matters a lot when it comes to which religion you’re supposed to join, and thus matters when it comes to questions like whether you think women should be treated like crap or not. But there are lots of ways our lives can be formed by things that ‘happen to us’, and it has come to my attention that one of the variables which has likely impacted me a lot over time is a factor I’ve only mentioned once or twice in passing in this context here on the blog. It deserves a bit more attention I think. It is of course my disease.
I shall admit from the outset that most of the effects are speculative, because in terms of what might be termed the personality-relevant range of my life, I’ve never lived without the disease; I got it at the age of two. The alternative scenario is very different to imagine. Nevertheless there are some things I’ve noticed along the way which I thought I should write down somewhere. Note that the disease can progress in many different ways and that the variation in outcomes both relate to inherent biological characteristica and individual behaviour; i.e. don’t read this like ‘the story of how diabetes affects people’ – I can only speak for myself.
Diabetes has without a doubt increased my level of risk aversion compared to the disease-free baseline. Diabetes can cause hypoglycemia, and severe hypoglycemia can cause brain damage or death. I’ve been close to those latter outcomes ‘a few times’; how many times depends a lot on stuff like how long the duration of unconsciousness/coma from hypoglycemia would have to be for you to consider it life-threatening and whether simply being admitted to the hospital with a hyperglycemia-related tonic–clonic seizure is significant enough to ‘count’. Most of the bad stuff’s in the past, I’ve had very few problems over the last 8 years or so, but in terms of how I behave I have some baggage here.
‘Openness to new experiences‘ and similar variables relate to risk aversion, so these traits have also likely been implicitly impacted. It’s hard to know how things would have played out differently if I hadn’t been sick, but these remarks are not just related to hypothetical effects; I know of some specific ways they had an impact on behaviour. One was that I drank quite rarely in the first years of high-school and did not ever spend the night someplace else (a common way to solve the logistics problems related to living far away from the action for a lot of other people (classmates, my brothers)), because I was afraid I’d actually die if I did something stupid. Perhaps even if I didn’t; the combination of alcohol and diabetes is hard to get right, especially when consuming the amounts people usually do in order to get drunk. If I hadn’t been too afraid to sleep elsewhere my parents would probably have said no, but they didn’t need to. Both my brothers were very different, but needless to say our differences don’t all relate to the disease.
Another closely related aspect is the level of control I need to have over events in order to feel comfortable. Some types of spontaneity are okay, but they all involve doing stuff you didn’t plan on doing – and if you’re not doing what you planned on doing, as a diabetic you almost always need to adjust insulin and take precautions. ‘Let’s go for a walk this afternoon’, my mom will say right after lunch – after I’ve taken insulin. I did not plan on going for a walk when I took the insulin, so now I either need to take some juice or glucose with me before joining my mom, to avoid hypoglycemia, or I need to tell her it would be better to postpone the walk a few hours. Just joining her without any adjustments is not an option. This is something she still forgets sometimes, btw., presumably because it’s easy to tell yourself that these days ‘he can always adjust the dosage’, whereas it’s a bit harder to remember that ‘dosage can not be adjusted after it has been injected’.
If I eat something I’ve never eaten before, I’m basically guessing what the effect will be on the blood glucose level. As a diabetic you get very good at this over time, because the link between the level of carbohydrate intake and the insulin requirement is more or less fixed, but you don’t always get it just right, also because of timing issues. For instance, I learned after a dinner and a trip to the movies with my big brother that the brown rice we had at his place affect my blood glucose in a different manner than the white rice I’d become accustomed to eating; I almost had a hypoglycemic incident in the cinema, because it turns out that the carbohydrates in brown rice take longer to impact blood glucose, meaning that the fast-acting insulin I’d taken to the meal was working before the food had really had a significant impact on my blood glucose. Another factor complicating matters a bit is that there are interaction effects here that people don’t usually think about (why would they?); for instance, fast acting carbohydrates will generally act slower (again postponing the insulin requirement) if they’re eaten together with food containing complex carbohydrates or fats. As long as you have full control over events and your environment, the kind of stuff that happened at the cinema just doesn’t happen, and every time you deviate from the plans you’ve made, you take on additional risk. Most of the time it’s worth it, but the extra risk is there and it needs to be managed and controlled. If the risk is particularly hard to control for some reason or another, it can make social isolation look like a more desirable state of affairs than it otherwise would. I mention this because my disease was very hard for me to control in my early highschool years, because of the hormonal changes which took place during that period, and I did tend to isolate myself from others to some degree, presumably at least in part as a consequence of that. One interesting sidenote here is that the additional risk related to participating in various social events that i faced also meant that other types of risk got a lower priority; when I attended the third year high school prom, my biggest worry was that I would have a hypoglycemic episode. It was a lot more present in my mind than the worry that some sweet girl would turn me down if I asked her to dance (..or whatever. I don’t dance.)
I don’t trust my body as much as other people do. The difference was probably a lot more pronounced earlier on, but it’s still a factor today. I know my body doesn’t always tell me the truth about how well I am, I know that I need to monitor it sometimes for it not to mess with me. I know that it has the potential to seriously mess with me, even though it would be very inconvenient for me if it were to happen. I’m implicitly much more aware of the link between behaviour and health than a completely healthy me would be, because my behaviour impacts my health literally on a day to day basis; if I don’t match insulin and behaviour, I will feel uncomfortable. I can not exclude the possibility that this distrust of myself and my own body has had spill-over effects on my social connections with others, making me less trusting generally, but this would be a much more theoretical effect on my personality than the others mentioned so far.
Guilt. Diabetes is all about tradeoffs. Generally, on the one hand we want Hba-1c, a rough measure of ‘average blood glucose’, to lie as closely to that of healthy individuals as possible. On the other hand, doctors don’t like to see diabetics in the emergency ward, which is where they tend to end up if they don’t care about anything except Hba-1c; it’s generally not possible to ‘normalize’ blood glucose completely due to side effects of the treatment. An Hba-1c close to the normal range will cause more frequent side effects in the short term, whereas disregarding Hba-1c to a significant degree in order to avoid all cases of hypoglycemia completely (including mild ones, which most well-regulated diabetics will have from time to time) will often eventually cause severe problems in the long run. How diabetics deal with these tradeoffs vary, but most of them will probably have some degree of guilt about not taking enough care of themselves. How well they deal with that guilt can have a significant effect on how well people manage their disease. I have felt much more guilty about my own behaviour in the past than I do now, and part of the reason is certainly that a lot of that guilt was misplaced, something I only later realized. Note that it isn’t just guilt about long-term stuff that goes into this; short term, everyday-life is relevant as well. If you get the dosis wrong, and sometimes you do, it will impact behaviour. If a diabetic is hyperglycemic, she might become more aggressive and irritable than she otherwise would be. Mild hypoglycemia might cause fatigue and difficulty concentrating. Disease affects behaviour, and it’s almost never ‘completely not your fault.’ So this is a factor too. Most of the very unpleasant arguments I’ve had with family members I’ve had while I was hyperglycemic; today I’ve learned to consider a ‘tendency to argue’ a symptom which needs to be checked out by means of a blood test. But even if you know that your disease affects your behaviour, it’s impossible to ignore the fact that your behaviour also affects your disease – so where does the blame go? Are drunk people blameworthy for what they do while they are drunk? The answer to such questions are not always clear-cut.
Last of all, death. I was quite early on made aware of the fact that I would not live forever. At the worst point during my high school years, I was in significant doubts as to whether I would still be alive at the age of 20-25; that’s the kind of thoughts that start going through your head when you wake up from a coma a couple of times a month in a hospital bed, and the doctor start asking questions like whether it’s okay if he scans your brain with the fancy MRI-machine to figure out if that last incident caused brain damage or not. Lots of young people think about death, but a lot fewer are forced to confront their own mortality by stuff outside their own control.
I’m very aware of the long-term damage that my disease might cause to me and I’ve always been. I think this is one of those things which has contributed to making me much less likely to engage with the opposite sex. Basically I had a ‘I’m sick and if she knew the truth about my condition, no right-thinking female would have anything to do with me and it would be deceitful of me to withhold that information from her’-approach to these things. Today I’m much less pessimistic, both about the health impact on dating outcomes and about my long-term prognosis, and I try not to make things harder for myself than they need to be in that respect – dating’s hard enough as it is. Thinking like that has been made easier by the fact that I’ve only had two diabetes-related hospitalizations over the last ~8-9 years or so, and neither of them were all that surprising in retrospect; they were both at least to a significant degree the results of other stuff going on in my life, not some freak out-of-the-blue episodes like some of those I had in the past. Which means that I’m much less fearful now and more open to experiment than I was at baseline (as long as I retain a sufficient level of control to feel relatively comfortable).
There’s a lot of stuff that goes into the question of which kind of person you end up becoming, and it’s probably harder to change yourself for the better if you don’t know how you came to become who you are. A significant problem is that we tend to pick narratives we prefer and the kind of explanations which best fit how we like the story to be told. But I still tend to believe observations like the above, even though effect sizes are unknown (unknowable?), are valuable.
There’s this question I’ve been asked many times: “Type 1 diabetes? Is that genetic?”
I was asked it again a couple of weeks ago and it caught me off-guard so I don’t think I was being quite as precise as I’d have liked to be – by having now written this post, I hope that I’ll do better next time (oh yes, there’ll be a next time…). Before going any further I should probably note here that even though I don’t know much about genetics, I estimate that I do know (/significantly?) more than most people who would choose to ask such a question: Having been exposed to stuff like Khan Academy, Razib Khan’s blog, Wikipedia (way too much to link to here), Russell, Dawkins and Majerus for instance means that I know the difference between a recessive allele and a linkage disequilibrium. It also means that I’m very inclined to answer a question like that one by asking another question: “What do you mean by ‘is it genetic?’” Genetics is complex stuff and there are many kinds of genetic disorders. I’ve tended to assume that people who ask do so more because of the implied blame-angle inherent in the question (‘it’s not your own fault you’re sick, right?’) than because of their deep interest in the disease etiology of type 1 diabetes – but I shouldn’t let that affect the way I respond, given that a reasonably clear answer to the question (…I assume they think they are asking) exists today (wikipedia):
“Type 1 diabetes is partly inherited and then triggered by certain infections, with some evidence pointing at Coxsackie B4 virus. There is a genetic element in individual susceptibility to some of these triggers which has been traced to particular HLA genotypes (i.e., the genetic “self” identifiers relied upon by the immune system). However, even in those who have inherited the susceptibility, type 1 diabetes mellitus seems to require an environmental trigger.”
So the simple version is that ‘genetics’ increases disease susceptibility and an infection then triggers the disease process. Here’s the abstract of a new study, Genetics of Type 1 Diabetes, by Steck and Rewers, providing a little more detail:
“BACKGROUND: Type 1 diabetes, a multifactorial disease with a strong genetic component, is caused by the autoimmune destruction of pancreatic β cells. The major susceptibility locus maps to the HLA class II genes at 6p21, although more than 40 non-HLA susceptibility gene markers have been confirmed.
CONTENT: Although HLA class II alleles account for up to 30%–50% of genetic type 1 diabetes risk, multiple non-MHC loci contribute to disease risk with smaller effects. These include the insulin, PTPN22, CTLA4, IL2RA, IFIH1, and other recently discovered loci. Genomewide association studies performed with high-density single-nucleotide–polymorphism genotyping platforms have provided evidence for a number of novel loci, although fine mapping and characterization of these new regions remain to be performed.
Children born with the high-risk genotype HLADR3/4-DQ8 comprise almost 50% of children who develop antiislet autoimmunity by the age of 5 years. Genetic risk for type 1 diabetes can be further stratified by selection of children with susceptible genotypes at other diabetes genes, by selection of children with a multiple family history of diabetes, and/or by selection of relatives that are HLA identical to the proband.
SUMMARY: Children with the HLA-risk genotypes DR3/4-DQ8 or DR4/DR4 who have a family history of type 1 diabetes have more than a 1 in 5 risk for developing islet autoantibodies during childhood, and children with the same HLA-risk genotype but no family history have approximately a 1 in 20 risk. Determining extreme genetic risk is a prerequisite for the implementation of primary prevention trials, which are now underway for relatives of individuals with type 1 diabetes.”
“Children born with the high-risk genotype HLADR3/4-DQ8 comprise almost 50% of children who develop antiislet autoimmunity by the age of 5 years” – in plain English, this means that almost half of all type 1 diabetics who show disease development before the age of 5 have this specific high-risk genotype. Note also how complex this disease is in terms of the genetics – ‘more than 40 non-HLA susceptibility gene markers have been confirmed’. Maybe some of them are just flukes due to p-value hunting, but that’s a lot of genes impacting disease risk.
Steno has some stuff in Danish here if people are interested. According to their numbers, if the mother has type 1 diabetes there’s a 2% risk that her child will have the disease. If the father has the disease the risk is 5%. Lægehåndbogen states that for monozygotic twins, if one twin develops the disease the risk that the other twin will also get it is 50%.
Here’s the link. If you have any interest in this subject, you should probably read all of it.
“We conducted a systematic review of literature on the CE of diabetes interventions recommended by the American Diabetes Association (ADA) and published between January 1985 and May 2008. We categorized the strength of evidence about the CE of an intervention as strong, supportive, or uncertain. CEs were classified as cost saving (more health benefit at a lower cost), very cost-effective (≤$25,000 per life year gained [LYG] or quality-adjusted life year [QALY]), cost-effective ($25,001 to $50,000 per LYG or QALY), marginally cost-effective ($50,001 to $100,000 per LYG or QALY), or not costeffective (>$100,000 per LYG or QALY). The CE classification of an intervention was reported separately by country setting (U.S. or other developed countries) if CE varied by where the intervention was implemented. Costs were measured in 2007 U.S. dollars.
RESULTS— Fifty-six studies from 20 countries met the inclusion criteria. A large majority of the ADA recommended interventions are cost-effective. We found strong evidence to classify the following interventions as cost saving or very cost-effective: (I) Cost saving — 1) ACE inhibitor (ACEI) therapy for intensive hypertension control compared with standard hypertension control; 2) ACEI or angiotensin receptor blocker (ARB) therapy to prevent end-stage renal disease (ESRD) compared with no ACEI or ARB treatment; 3) early irbesartan therapy (at the microalbuminuria stage) to prevent ESRD compared with later treatment (at the macroalbuminuria stage); 4) comprehensive foot care to prevent ulcers compared with usual care; 5) multi-component interventions for diabetic risk factor control and early detection of complications compared with conventional insulin therapy for persons with type 1 diabetes; and 6) multi-component interventions for diabetic risk factor control and early detection of complications compared with standard glycemic control for persons with type 2 diabetes. (II) Very cost-effective — 1) intensive lifestyle interventions to prevent type 2 diabetes among persons with impaired glucose tolerance compared with standard lifestyle recommendations; 2) universal opportunistic screening for undiagnosed type 2 diabetes in African Americans between 45 and 54 years old; 3) intensive glycemic control as implemented in the UK Prospective Diabetes Study in persons with newly diagnosed type 2 diabetes compared with conventional glycemic control; 4) statin therapy for secondary prevention of cardiovascular disease compared with no statin therapy; 5) counseling and treatment for smoking cessation compared with no counseling and treatment; 6) annual screening for diabetic retinopathy and ensuing treatment in persons with type 1 diabetes compared with no screening; 7) annual screening for diabetic retinopathy and ensuing treatment in persons with type 2 diabetes compared with no screening; and 8 ) immediate vitrectomy to treat diabetic retinopathy compared with deferred vitrectomy.
CONCLUSIONS — Many interventions intended to prevent/control diabetes are cost saving or very cost-effective and supported by strong evidence. Policy makers should consider giving these interventions a higher priority.”
In health cost-effectiveness analyses, it’s quite common to find measures/interventions that are cost-effective but do not actually save ‘you’ money, because the effectiveness variable is some sort of (/weighted) effect/$ measure. There’s also always the problem with figuring out what’s the relevant alternative course of (in-?)action. But what I found very, very interesting here is that one of these interventions was actually cost-saving when compared to doing nothing:
This is very interesting. Of course it’s also noteworthy that quite a few other treatment options would actually be cost saving if implemented on a larger scale than is currently the case. I should probably also comment on some of the stuff that’s not worth the money:
“The four interventions with strong evidence of not being cost-effective were 1) one-time universal opportunistic screening for undiagnosed type 2 diabetes among those aged 45 years and older compared with no screening; 2) universal
screening for type 2 diabetes compared with targeted screening; 3) intensive glycemic control in the U.S. setting for patients diagnosed with diabetes at older ages (55–94 years of age) compared with usual care; and 4) annual screening for retinopathy compared with screening every two years. All these studies were for type 2 diabetes.”
Some sort of universal opportunistic screening program is one of those things that might sound like a good idea, but probably isn’t. It’s just too damn expensive. Btw., when applying age-targeting approaches it’s not at all clear where to place the cut-off point:
“Current evidence is uncertain on how the CE of screening for undiagnosed type 2 diabetes would change with the age of
those screened. Two studies evaluated the CE of screening for undiagnosed type 2 diabetes; one study reported that costeffectiveness ratios (CERs) increased with initial screening age (16) while the other reported that they decreased with screening age (35).”
1. From Aerobic Exercise Capacity and Pulmonary Function in Athletes With and Without Type 1 Diabetes, by Komatsu et al. (link):
“In this study, we have shown that athletes with type 1 diabetes have a Vo2peakmax [aerobic exercise capacity] similar to that of athletes without diabetes but a lower anaerobic threshold than that of athletes without diabetes.
In a previous study (6), we demonstrated that nonathletic type 1 diabetic patients have a lower Vo2peak max than healthy subjects. In the present study, we confirm these data in nonathletic type 1 diabetic patients, but the defect (low Vo2peak max) was not found in athletes with type 1 diabetes. These data are in accordance with a study (11) that compared 128 patients with long-duration type 1 diabetes and 36 healthy individuals. [...]
All of the individuals in this study went to heart rate max frequency during the test. However, the type 1 diabetes sedentary group had lower maximum heart rate than the control group, as expected. This was an interesting finding and one in accordance with our previous data (6) in which the diabetic group showed lower maximum frequency during exercise than normal control subjects. This defect could be corrected with regular exercise since the diabetic athlete was able to achieve the same maximum heart rate as a normal athlete.
In this study, we also found that FEV1 [volume that has been exhaled at the end of the first second of forced expiration] was decreased in type 1 diabetic athletes compared with other groups. [...] Abnormalities in lung elasticity behavior can be manifestations of widespread elastin and collagen abnormalities in type 1 diabetic patients (14). These alterations have been demonstrated in diabetes and are, in some respects, similar to those that occur during normal aging.”
I found the ‘lower anaerobic threshold’ particularly interesting as this threshold can probably be considered a significant limiting factor when you run (/half-)marathons and similar. If the threshold is lower, the inevitable buildup of lactic acid will start sooner or at a lower absolute activity level, meaning you simply can’t run as fast.
2. A follow-up on the All-Cause Mortality Trends in a Large Population-Based Cohort With Long-Standing Childhood-Onset Type 1 Diabetes study from ‘The Allegheny County Type 1 Diabetes Registry’, a previous version of which I’m pretty sure I’ve linked to before, has now been done, adding 9 more years of follow-up to the analysis. Here’s the link. Conclusions:
“Although survival has clearly improved, those with diabetes diagnosed most recently (1975–1979) still had amortality rate 5.6 times higher than that seen in the general population, revealing a continuing need for improvements in treatment and care, particularly for women and African Americans with type 1 diabetes.” [...]
“Of note, now with a range of 28–43 years of type 1 diabetes duration, the risk of dying is 7 times higher than that of the local general population, with signiﬁcant improvements in SMR [Standardized Mortality Ratios, US] for those with diabetes diagnosed most recently in this cohort.” [...] This is the largest population-based type 1 diabetes cohort with at least 25 years of follow-up in the U.S. A recent population-based 20-year follow-up study in New Zealand showed the highest SMRs in individuals with type 1 diabetes diagnosed at age <30 (3.3 for men and 4.3 for women) (14). A nationwide Norwegian cohort with childhood-onset (age <15 years) type 1 diabetes recently reported SMRs of 3.9 (male) and 4.0 (female) after 20 years of follow-up (6)."
So what does this look like? The short version is this:
Graph number 3 directly above graphs the survival probability for the groups diagnosed during 65-69, 70-74 and 75-79; as can be seen quite clearly mortality is lower for the people diagnosed later in time, reflecting the progress that has taken place in treatment options and management of the disease. Note that these are not ‘historical figures’ – I got diagnosed in 87, just 8 years after the last of these cutoffs.
The US is quite different from the other countries analyzed in a few respects, in particular when it comes to the outcomes of the females: “The respective male-to-female mortality RRs [rate ratios, US] for these studies are 1.23 in New Zealand, 2.26 in Norway, and 1.29 in the U.K compared with 0.80 for our study. The reason for this discrepancy is unclear, but it appears that female sex completely lost its general survival advantage in our diabetes population. [...] Women in our cohort die at a rate similar to that of men, a result warranting further exploration, as younger women die much less frequently than younger men in the general U.S. population.”
What about race, I hear you ask? Well: “Despite race being a signiﬁcant predictor of mortality within the Allegheny County cohort (hazard ratio 3.2), no differences in SMR were seen by race, the African American SMR tending to be lower than the Caucasian SMR during follow-up (Fig. 2C). This seemingly contradictory result can be explained by the extremely high mortality rates seen in young African-Americans in the general population, particularly resulting from violent deaths (20)”
3. Changes in the Incidence of Lower Extremity Amputations in Individuals With and Without Diabetes in England Between 2004 and 2008, by Vamos et al. (link). From the study:
“RESEARCH DESIGN AND METHODS We identified all patients aged >16 years who underwent any nontraumatic amputation in England between 2004 and 2008 using national hospital activity data from all National Health Service hospitals. Age- and sex-specific incidence rates were calculated using the total diabetes population in England every year. To test for time trend, we fitted Poisson regression models.
RESULTS The absolute number of diabetes-related amputations increased by 14.7%, and the incidence decreased by 9.1%, from 27.5 to 25.0 per 10,000 people with diabetes, during the study period (P > 0.2 for both). The incidence of minor and major amputations did not significantly change (15.7–14.9 and 11.8–10.2 per 10,000 people with diabetes; P = 0.66 and P = 0.29, respectively). Poisson regression analysis showed no statistically significant change in diabetes-related amputation incidence over time (0.98 decrease per year [95% CI 0.93–1.02]; P = 0.12). Nondiabetes-related amputation incidence decreased from 13.6 to 11.9 per 100,000 people without diabetes (0.97 decrease by year [0.93–1.00]; P = 0.059). The relative risk of an individual with diabetes undergoing a lower extremity amputation was 20.3 in 2004 and 21.2 in 2008, compared with that of individuals without diabetes. [...]
In summary, in this study we found no evidence that the incidence of amputations has significantly decreased over the last 5 years among people with diabetes in England. In contrast to the results from regional studies in England, the population burden of amputations increased in people with diabetes at a time when both the number and incidence of amputations decreased in the aging general population. There is strong evidence to support the fact that much of this burden is preventable through existing interventions, and our findings highlight the need to further improve foot care for people with diabetes.”
“Purpose: Diabetic retinopathy is characterised by morphological lesions secondary to retinal vascular impairment, and it is assumed that changes in the diameter regulation of retinal arterioles are involved in the disease pathogenesis. It has previously been shown that prostaglandin F2α can constrict retinal arterioles in vitro. In the present study, we investigated whether a similar effect could be achieved by topical administration in diabetic patients with dilated retinal arterioles and retinopathy.
Methods: Twenty-two type 1 diabetic patients with mild retinopathy and twenty-four matched normal controls were randomized to topical treatment with the prostaglandin F2α agonist latanoprost twice daily for 1 week, followed by similar treatment with the cyclo-oxygenase inhibitor diclofenac, or to receive the two medications in the reverse order. The Dynamic Vessel Analyzer was used to assess the effect of the interventions on the resting diameter of retinal vessels and on the diameter response of retinal arterioles to increased blood pressure (BP) induced by isometric exercise and flicker stimulation.
Results: Latanoprost reduced the resting diameter of retinal arterioles significantly in patients with diabetes (p = 0.01), but had no effect on normal persons. Diclofenac had no effect on the resting diameter of arterioles in either of the groups. The diameter responses to increased BP and flicker stimulation were not significantly changed by any of the treatments.
Conclusion: Long-term prospective studies are needed to study the effect of topical treatment with latanoprost on the consequences of retinal hyperperfusion in retinal vascular diseases such as diabetic retinopathy.”
So, to Plamus and others who might have no idea what I’m talking about, I participated in this study and wrote a couple of short posts about it back then. Only yesterday I incidentally asked Kathrine to send me the study and kindly enough she did – but I’ll not put it up here.
Diabetic retinopathy is a much feared complication to diabetes. It is ‘the most frequent cause of blindness of adults in the age of 20-74′ in Denmark. So far the usual approach to dealing with this complication has been (still is) to screen diabetics by taking pictures of their eyes at regular intervals (once every year) and then intervene when complications become significant enough to ‘merit attention’, so to speak – usually by means of surgical intervention. One of the main reasons why the screening protocol is implemented, in case you were wondering, is that patients will often have no symptoms even relatively late in the process – you basically don’t get any symptoms before you get bleeds in your eyes significant enough to cause potential vision loss. Katrine’s approach was to figure out if two extant and in other areas widely used pharmacological treatment options could help delay the progression of the damage to the eyes caused by diabetes.
To make a long story short, Latanoprost showed promise in the study, so now Toke Bek, Kathrine’s phd-advisor, has decided to do a long-term study using the drug. Unless I am currently greatly underestimating the long-term risks of complications from participating (have yet to read up on those), I’ll participate in that trial as well.
Lots more here. I also took a personal interest in this short but neat and instructive video:
Btw, I just went and made myself an account to Khanacademy. I consider it quite likely that I’ll visit the site more frequently in the future than I used to do. If I do I’ll do my best to remember to post on my progress here as well.
The site has a lot of data on your progress and I like that kind of stuff. For instance now I know that I’ve spent 50 minutes today on the site (maybe information like that could potentially cause me to cut down on my time consumption of a good like this, but I actually don’t think that is in any way the most likely outcome..).
Epidemiology of Chronic Wound Patients and Relation to Serum Levels of Mannan-binding Lectin, by Bitsch, Laursen et al (2009):
“The aim of this study was to describe the epidemiology of chronic wounds in a large cohort of patients from a tertiary hospital out-patient clinic, and examine the significance of serum mannan-binding lectin for the occurrence and clinical presentation of such wounds.The study comprised 489 consecutive patients with chronic foot and leg ulcers. A clinical classification of wound-aetiology was performed, and mannan-binding lectin was measured in the sera of patients and healthy controls. The patients presented with 639 wounds altogether; diabetic foot ulcers (309), venous leg ulcers (188), arterial ulcers (109), and vasculitis (33).”
[The people doing the study are from Copenhagen Wound Healing Center. Notice how many of the patients are diabetic? That's not a coincidence]
“Mannan-binding lectin (MBL) is an important component of the humoral innate immune system, and MBL possesses several characteristics indicating that it may play an essential role in wound healing; i.e. modulating inflammation and contributing to the clearance of microorganisms and apoptotic cells (3, 4). Deficiency in MBL might therefore contribute to prolonged healing.” [...] “Whether MBL plays a direct role in prevention or reduction of the “bio-burden” of chronic wounds is unclear. Chronic wounds colonised with bacteria are often neither infected nor inflamed, and when infection does appear antibiotic treatment will be initiated immediately – or may even have been given prophylactic. This indicates that MBL – shown to be associated with susceptibility and severity of infections – primarily functions upstreams to the manifestation of the chronic leg ulcer as different mechanisms appear to initiate and maintain the leg ulcer.” [...] “Like other immune components MBL may act as a double-edged sword; in some clinical contexts MBL deficiency may be advantageous as protection against complement-mediated tissue injury. Studies of patients with type 1 diabetes have shown significantly elevated levels of MBL to be positively correlated with markers of renal complications and nephropathy (26, 27), possibly indicating that MBL may play a pathogenetic role or be a risk factor in type 1 diabetes. Diabetic foot ulcer is most frequently presented by type 2 diabetics, who also constitute the majority of patients in the present study. A follow-up study of Danish type 2 diabetics showed their risk of dying to be significantly correlated to high MBL, indicating an implication in diabetic vascular complication (28). Whether such MBL-associated vascular complications also contribute to the development of chronic foot ulcer in diabetic patients needs further investigation.
In conclusion, in a cohort of chronic foot and leg ulcer patients with different aetiological backgrounds, those with ulcers due to venous insufficiency, alone or in combination with other aetiologies, expressed significantly lower MBL concentrations than the healthy controls. The inverse pattern was seen in diabetic and arterial ulcer patients, who expressed significantly higher MBL levels. This indicates different roles for MBL in the development of ulcers in the different groups of patients; and the significant correlation of MBL deficiency to venous leg ulcer suggests that MBL substitution might be a relevant therapy for this group of patients.”
Basically there seems to still be a lot of work to be done and a lot of stuff ‘we’ (the experts that is, I’m not including myself in that ‘we’…) don’t understand, or at least don’t know for certain if they know yet, but someone are actually doing some of that work right now. As someone who might benefit from this research, all I can say is: Just keep working you guys!
“OBJECTIVE Hippocampal neurons in adult animals and humans are vulnerable to severe hypoglycemia and hyperglycemia. Effects are hypothesized to be exacerbated during development, but existing studies on developing human brains are limited. We examined whether hypoglycemia or hyperglycemia experienced during brain development in humans affects hippocampal volumes.
RESEARCH DESIGN AND METHODS We analyzed T1-weighted magnetic resonance images in 95 youth with type 1 diabetes and 49 sibling control subjects aged 7–17 years. Youth with diabetes were categorized as having 0 (n = 37), 1–2 (n = 41), or 3 or more (3+; n = 17) prior severe hypoglycemic episodes. Hyperglycemia exposure was estimated from median lifetime A1C, weighted for duration of diabetes. Stereologic measurements of hippocampal volumes were performed in atlas-registered space to correct for whole brain volume.
RESULTS Greater exposure to severe hypoglycemia was associated with larger hippocampal volumes (F [3,138] = 3.6, P = 0.016; 3+ larger than all other groups, P < 0.05). Hyperglycemia exposure was not associated with hippocampal volumes (R2 change = 0.003, F [1,89] = 0.31, P = 0.58, semipartial r = 0.06; one outlier removed for high median A1C), and the 3+ severe hypoglycemia group still had larger hippocampal volumes after controlling for age of onset and hyperglycemia exposure (main effect of hypoglycemia category, F [2,88] = 6.4, P = 0.002; 3+ larger than all other groups, P < 0.01).
CONCLUSIONS Enlargement of the hippocampus may reflect a pathological reaction to hypoglycemia during brain development, such as gliosis, reactive neurogenesis, or disruption of normal developmental pruning."
"Greater exposure to severe hypoglycemia during childhood was associated with enlargement of hippocampal gray matter volume in youth with type 1 diabetes. This effect was not explained by age, sex, degree of hyperglycemia exposure, age of onset, or duration of disease and was equivalent for both hemispheres. Although the direction of the effect was unexpected, the fact that the subset of youth with three or more severe hypoglycemic episodes in their past was different from all other groups, including sibling control subjects, supports the sensitivity of the hippocampus to effects of repeated hypoglycemic episodes during brain development. These data do not support the idea that chronic hyperglycemia in childhood affects gray matter volume in the hippocampus."
From a new study, Hippocampal Volumes in Youth With Type 1 Diabetes, by Hershey, Perantie, Wu, Weaver, Black and White (no, I’m not making those last two names up, go take a look at the link).
If I’d participated in the study, I’d have been in the 3 or more group (the ‘more group’ part of the ’3 or more group’, to be more specific).
From an interesting study about a subject I’ve wondered about from time to time:
“OBJECTIVE—To compare the risk of cardiovascular disease (CVD) death and the impact of hyperglycemia on the risk of CVD mortality associated with type 1 diabetes to that associated with type 2 diabetes.
RESULTS—During an 18-year follow-up, 86 participants with type 1 diabetes, 567 participants with type 2 diabetes, and 252 nondiabetic participants died. CVD mortality rates per 1,000 person-years were 23.1 (95% CI 16.9–31.9) in type 1 diabetic, 35.3 (30.8–40.4) in type 2 diabetic, and 4.6 (3.8–5.7) in nondiabetic participants. Adjusted hazard ratios for CVD mortality in participants with type 1 diabetes versus no diabetes was 3.6 (95% CI 2.2–5.7) in men and 13.3 (6.9–22.5) in women and in participants with type 2 diabetes versus no diabetes 3.3 (2.5–4.5) in men and 10.1 (6.7–17.4) in women. An increment of 1 unit (%) of GHb increased CVD mortality by 52.5% (95% CI 28.4–81.3) in type 1 diabetic subjects and by 7.5% (4.3–10.8) in type 2 diabetic participants.
CONCLUSIONS—The impact of type 1 and type 2 diabetes on CVD mortality was similar. The effect of increasing hyperglycemia on the risk of CVD mortality was more profound in type 1 than in type 2 diabetic subjects.”
Do note that the age of onset of diabetes was >30 years in both groups, so the relevance of the results when it comes to my own situation (diagnosis at the age of 2) is still questionable. Of course this is only speculation on my part, but one reason I can think of why the impact of hyperglycemia is ‘more profound in type 1′ patients might be that type 2 diabetics already have a lot of risk factors (obesity, ‘life style’, ect.), so that the effect of one more risk factor mean marginally less than it does among type 1 patients. If you’re already fat and sedentary and have been for many years, which most type 2 patients statistically are, adding hyperglycemia will not impact your risk of CVD-risk much, as it’s probably already through the roof; if you’re a sedentary type 2 diabetic with a BMI > 30 who also smokes daily, we’re not talking about the likelihood of dying from CVD, we’re only talking about when it’ll happen.
The part below is a good way to illustrate that the two diseases, type 1 and type 2 diabetes, are not all that similar, or at least that the patients are not all that similar:
“At baseline type 1 diabetic participants, when compared with nondiabetic participants, were leaner and had higher HDL cholesterol and lower diastolic blood pressure, but they had a slightly higher prevalence of hypertension, higher systolic blood pressure, and higher content of urinary protein than nondiabetic participants. Type 2 diabetic participants, when compared with nondiabetic participants were older, heavier, and more often nonusers of alcohol and had a higher frequency of hypertension, higher systolic and diastolic blood pressure, lower HDL cholesterol, higher triglycerides, higher content of urinary protein, and higher estimated creatinine clearance. Type 1 diabetic participants, when compared with type 2 diabetic participants were younger, leaner, and less frequently nonusers of alcohol and had lower prevalence of hypertension, lower diastolic and systolic blood pressure, higher HDL cholesterol, lower triglycerides, longer duration of diabetes, and lower estimated creatinine clearance.”
Some of these differences are probably sample-related, but not all of them. Note that despite being leaner and having more of the ‘good cholesterol’, type 1 diabetics still had worse kidney function than ‘healthy people’. That kidney damage is disease-related, not life-style related, and it’s quite likely that the patients had higher HDL cholesterol (and were leaner?) because they on average eat (live?) healthier than people who aren’t sick – that’s after all what they’re supposed to do. The ‘diabetic = fat guy who asked for it’ heuristic doesn’t work when we’re talking about the type 1s.
For et år siden deltog jeg i en øjenundersøgelse som jeg også omtalte her på bloggen. Jeg fik for ikke så længe siden et brev fra lægen som stod for studiet. I brevet stod bl.a.:
“Vi har analyseret data, og har fundet at øjendråberne påvirker blodgennemstrømningen i nethindens blodkar. Derfor kan de muligvis være en behandlingsmulighed for diabetisk øjensygdom i fremtiden.”
Det er godt nyt! I brevet fremgik det også, at et nyt studie er påbegyndt, som vil undersøge et tredje præparat. Jeg regner også med at deltage i dette studie og har udtrykt min interesse i at deltage.
With respect to diabetes, it’s now understood that several types of cancer are more common: colon, pancreas, and breast.
Link, the main topic of the article is the hypothesized link between injections of insulin analogs and cancer.
My granddad on my father’s side died of colon cancer, so that one already runs in the family. This link has some information about the genetics of that disease.
A very good lecture:
Jeg ville egentligt have gjort dette til en mere bred post om sundhedsdata, men jeg kom til at gå ud ad en tangent, og posten herunder er så, hvor jeg havnede. Først et kig på diabetesprævalensen i et internationalt perspektiv:
Jeg vidste ikke på forhånd, om jeg ville skrive posten på dansk eller engelsk, så jeg valgte at konstruere graferne på engelsk, anyway… De første to lande er Australien og Østrig, SR er Slovakiet, Kor er (Syd)korea – jeg håber de øvrige giver sig selv, ellers spørg. Kilden er OECD, rådata kan findes her. Der er også meget mere data af samme type ved dette link til OECD’s sample over helbredsrelaterede nøgleindikatorer, som jeg også tidligere har linket til.
Bemærkelsesværdigt for mange vil det nok være, at USA end ikke er i nærheden af at være i toppen af listen over diabetesrater. Jeg ved ikke om det er opgørelsesmetoden, der spiller ind her, men dette er i hvert fald overraskende. Mange lande, i dette udsnit Schweiz, Mexico, Ungarn, Canada, Tyskland, Tjekkiet og Østrig, har højere absolut prevalens, og de fleste af de samme lande ligger ligeledes på niveau eller højere i de alderskorrigerede data (her skiller især Mexico sig ud fra resten). Bemærk at mellemindkomstlande i efterhånden nogle år har oplevet stor vækst i incidensen af type 2 diabetes, og at både Kina og Indien i disse år også oplever voldsom vækst. Livsstilssygdomme holder sig ikke længere til de rige lande.
Jeg fandt også nedenstående interessant (data er fra OECD’s nøgleindikatorer):
Pr. 100.000 indbyggere er på en måde en god variabel, på en måde en dårlig variabel at anvende. Den er god, fordi den angiver en form for (meget) løst estimat for, hvor udbredt sygdommen er (ja, det, der måles, er hvor mange, der dør af sygdommen; men disse to variable følges altså ret godt ad – det må synes en rimelig antagelse, at ‘den marginale nydiagnosticerede diabetiker’ ikke vil introducere væsentlige nye effekter af interesse på populationsniveau, som vil lede til signifikante afvigelser på mortalitetsraterne på tværs af diabetespopulationen som helhed på langt sigt, selvom han eller hun rigtigt nok gør på kort sigt, se også ndf.). Den er dårlig, fordi den overser modsatrettede effekter, som i perioden utvivlsomt har spillet en rolle. Hvis man ønskede kun at fange mortalitetsudviklingen og således prøve at omgå problemet prævalensvariationen (-væksten) over tid udgør, ville døde pr. 1000 diabetikere eller lignende være et bedre mål, selvom det selvfølgelig også er problematisk at anvende, eksempelvis fordi risikoen for komplikationer vokser over tid og derfor på ingen måde er homogen i gruppen af diabetikere, et forhold mortalitetsstudierne altid tager (og bør tage) højde for.
Det er vanskeligt at sammenligne tallene fra 1960 med tallene fra i dag, for mange ting har ændret sig, og en del af disse har utvivlsomt medvirket til at gøre det problematisk at sammenligne tallene over tid uden at tage nogle betydelige forbehold. Det giver mening, at flere i dag dør af diabetes, fordi flere i dag har diabetes, men for bare at tage tre markante problemer, så a) har patologernes praksis ændret sig i perioden, b) diabetes var mere dødelig for 50 år siden, end sygdommen er i dag, fordi vores viden om sygdommen og vores behandlingsmuligheder er udvidet markant, og c) det er uklart, hvor stor forskel de markante fremskridt i diagnosticeringsprocessen (måling af glykeret hæmoglobin, brugen af plasma-glukose værdier), såvel som de deraf følgende ændrede diagnostiske praksis, har betydet for disse tal. Tallene er i den meget lave ende, og det vil de fleste af den slags opgørelser være: Mange diabetesdødsfald er vanskelige at kategorisere den ene eller den anden vej. Mere end 80 % af diabetikerne herhjemme dør af hjertekar-sygdom, men det er umuligt for en patolog at vide med sikkerhed, om hr. Hansen fik sin blodprop pga. sin diabetes, eller om han havde fået den alligevel. Hvis tallene stammer alene fra eksempelvis dødsårsagsregistret, vil de undervurdere diabetes’ betydning for mortaliteten betydeligt, en observation der for øvrigt er righoldig empirisk belæg for at gøre sig (Mühlhauser, Sawicki m.fl.). Observationen betyder også, at der nok i opgørelser som disse vil være en tendens til kun at anvende/acceptere diabetes som dødsårsag i de mest oplagte tilfælde (de mest oplagte vel nok værende DKA, diabetisk hypoglykæmi (estimeret 2-4% af alle dødsfald blandt diabetikere), hyperosmolær non-ketotisk koma og nyresvigt sekundær til diabetes), og så se bort fra diabetes som forklaringselement i tilfælde som er vanskeligere at kategorisere.
Hvis man holder sig alene til disse tal, koster diabetes lidt under 900 mennesker livet herhjemme hvert år, ud af ca. 55.500 døde i alt – det omtrentlige tal for 2006, det sidste år hvor data er tilgængelige i OECD-regi, jf. dst – svarende til ca. 1.6 %. Det tal er meget, meget lavt, og estimaterne på dette område varierer da også ganske betydeligt. Den internationale diabetesforening IDF estimerede således tidligere dette efterår, at 2.744 danskere i 2010 vil dø på grund af diabetes (linket er her – men det er en elendig artikel, og jeg vil anbefale dig ikke at følge linket, da det estimat er omtrent artiklens eneste ‘formildende omstændighed’, så at sige). Det estimat er måske tættere på sandheden, men der er som sagt mange usikkerhedselementer her som gør evaluering af sådanne estimater vanskelig.
Herunder følger en række studier jeg enten har kigget nærmere på inden for de sidste par måneder, eller der som minimum har fanget min interesse i en sådan grad, at jeg har gemt et link til dem, med henblik på at læse dem på et senere tidspunkt. Jeg vil formodentligt indkorporere dem og resultaterne i mine to store posts om diabetes (som du kan læse her og her), men har ikke rigtigt fundet tid til det endnu:
1) Mortality from heart disease in a cohort of 23,000 patients with insulin-treated diabetes. Undersøgelsen er fra England, og er baseret på et meget omfattende kohort-studie af britiske type 1 diabetikere, der desværre ikke synes at være frit tilgængeligt online.
Jeg har ledt noget efter sådanne studier, og har kunnet konstatere – som det også fremgår af de studier, der rent faktisk er foretaget – at der er lavet meget få undersøgelser specifikt af unge type 1 diabetikeres mortalitet i et fremadrettet perspektiv, som undersøger patienterne i udgangspunktet og så i øvrigt også følger dem over tidsintervaller lange nok til at få nogle resultater, der faktisk kan bruges til noget. Dette studie er et af dem, og det følger amerikanske diabetikere fra Pennsylvania over 3 årtier.
2a) Long-Term Mortality and Incidence of Renal Dialysis and Transplantation in Type 1 Diabetes Mellitus. Dette er et andet af de få studier, der har kigget nærmere på type 1 diabetikeres mortalitet på langt sigt – dette studie følger østrigske patienter fra Lainz Hospital, Wien, over to årtier, med særlig fokus på udviklingen af nyrekomplikationer blandt patienterne.
2b) Long-term mortality in a nationwide cohort of childhood-onset type 1 diabetic patients in Norway. Studiet er det nyeste af sin art, jeg har kunnet finde (fra 2006), og det inkluderer alle norske type 1 diabetikere diagnosticeret inden deres 15. leveår i perioden fra 1973-82 (n=1906). Norsk og dansk diabetesbehandling er, i hvert fald i et internationalt perspektiv, relativt ens, så det er formodentligt, i kraft af kombinationen af dette forhold og undersøgelsens alder, det nærmeste man som dansk diabetiker kommer en samlet opgørelse over disse variable, der med nogen varsomhed kan overføres til danske forhold i et relativt nutidigt perspektiv.
2c) Mortality of patients with childhood onset (0-17 years) Type 1 diabetes in Israel: a population-based study*. Dette er, som du nok kan gætte, et fjerde af den slags mortalitetsstudier, der her omfatter israelske diabetikere. Samtlige israelske diabetikere diagnosticeret inden 18. leveår i perioden fra 1965 og frem til 1993 er inddraget i studiet, og dødsårsagerne søgt klarlagt.
2d) Long-Term Mortality in Nationwide Cohorts of Childhood-Onset Type 1 Diabetes in Japan and Finland. Dette er et sammenligneligt studie, der sammenligner dødeligheden for type 1 diabetikere diagnosticeret i barndommen i Finland og Japan over en årrække. Det er et omfattende studie med n ~ 7000. Finland er det land i verden med den højeste incidens af type 1 diabetes, og Japans incidens er til gengæld meget lav i en international sammenhæng, så på den måde er det bestemt ikke kun de forskellige sundhedssystemer, der har medvirket til at forårsage den markante forskel i prognosen for patienterne i de to lande, som dette studie finder (hvis en læge kun sjældent ser en bestemt sygdom blandt patienterne, er han eller hun alt andet lige mindre tilbøjelig til at mistænke den pågældende sygdom for at ligge bag symptomerne, og det tager længere tid at stille diagnose. For en diabetiker der indlægges med ketoacidose kan denne forlængede diagnoseperiode koste patienten livet. Der er også learning curve effekter. Og så videre…). Hvor stor forskellen var mellem to industrialiserede og moderne samfunds patienters prognose, var for mig meget overraskende.
3) HDL Composition Predicts New-Onset Cardiovascular Disease in Patients With Type 1 Diabetes. For så vidt er det bare en kort rapport på et par sider, men den er alligevel interessant, for selvom jeg godt kendte lidt til dyslipidæmis betydning for risikoen for kardiovaskulære events, har jeg på ingen måde sat mig nærmere ind i detaljerne.
4) Weight Loss in Type 2 Diabetic Patients. For at gøre en lang historie kort: Diabetikere har vanskeligere ved at tabe sig end ikke-diabetikere. Det er ikke noget nyt resultat, men det er et væsentligt forhold, jeg ikke har været inde på i min oprindelige artikel om type 1 og type 2 diabetes. Hvis du venter med at tabe dig, til du har fået dit første hjerteanfald som følge af type 2 diabetes, så får du pokkers svært ved at tabe dig efterfølgende – det er faktisk meget lettere at opnå et varigt vægttab, hvis du starter ud før du mere eller mindre har ødelagt din krop med fed mad og fysisk inaktivitet gennem mange år. Ja, jeg lyder frelst, men læs min artikel om de diabetiske senkomplikationer i sin helhed, før du dømmer mig. Og husk så på, at artiklen ikke er færdig endnu, og derfor stadig mangler at dække flere yderst væsentlige komplikationer i detaljer.
5) Reliability of causes of death in persons with Type I diabetes. Løst relateret til studierne 2-2d er dette et tysk studie fra 2002, der har kigget nærmere på dødsfald blandt type 1 diabetikere, og sammenlignet resultaterne af et undersøgelsespanels konklusioner med de udstedte dødsattester. Grundlæggende finder studiet, at diabetes som primær- og sekundær dødsårsag er underrapporteret i dødsattesterne blandt type 1 diabetikere, eller sagt på en anden måde; at type 1 diabetes koster flere leveår/liv end vi vil kunne læse ud af statistikkerne, hvis disse er baseret på de officielle dødsattester, hvad langt de fleste af den slags opgørelser er.
6) Mid- and Late-Life Diabetes in Relation to the Risk of Dementia – A Population-Based Twin Study. Studiet finder at diabetikere har forhøjet risiko for alle former for demens:
In GEE models [Generalized Estimating Equations], diabetes was associated with adjusted odds ratios (ORs) (95% CI) of 1.89 (1.51–2.38) for dementia, 1.69 (1.16–2.36) for Alzheimer’s disease, and 2.17 (1.36–3.47) for vascular dementia.
Jeg ville i øvrigt gerne i forlængelse af ovenstående læse nedenstående studie i sin helhed, men har været ude af stand til at finde en frit tilgængeligt udgave online, og jeg nægter at betale for det. Det kunne sandsynligvis uddybe:
Diabetes mellitus is associated with moderate cognitive deficits and neurophysiological and structural changes in the brain, a condition that may be referred to as diabetic encephalopathy. Diabetes increases the risk of dementia, particularly in the elderly. The emerging view is that the diabetic brain features many symptoms that are best described as “accelerated brain ageing.”
Når diabetikeres blodkar generelt bliver gamle før tid, giver det god mening at hjernen også gør det. Det er dog, så vidt jeg har kunnet forstå, uklart hvilken rolle den tilførte insulins interaktion med hjernecellerne spiller her.
Jeg har fået resultaterne fra den øjenscreening jeg fik foretaget for et stykke tid siden. Resultatet: Det kan nu for første gang ses på mine øjne, at jeg har diabetes. Efter 21 år uden forandringer, er de første nu dukket op. Selvom forandringerne er nogen alle (diabetikere) får, hvis de lever længe nok, og de er stærkt variable over tid og almentilstand (forbigående højt blodtryk eller højt blodsukker kan, som jeg har forstået det, have indflydelse på testresultaterne) og de således mest er at sammenligne med rynker, hvilket var den analogi, lægen brugte, da jeg fik forelagt resultaterne, er det lidt træls at få at vide, at man har fået sine første “rynker” som 23-årig.
Givet resultaterne af undersøgelsen vil Tilma godt have mig med i sit projekt. Jeg skal nok skrive mere herom løbende.
Here follows a collection of diabetes studies that I at some point have read/skimmed and considered interesting and informative, and well, relevant for my own future health prognosis:
1. Mortality trends among diabetics. A study on 1,075 patients with early onset (<18 years old at the time of diagnosis) type 1 diabetes.
3b. -ll- (part II)
4. Vision loss and diabetic retinopathy (in Danish). Also contains a few Danish numbers on type 1 diabetes and mortality.
9. Prevalence and predictors of sexual dysfunction in patients with type 1 diabetes. (do notice that the sample might be biased. Are diabetics living in a stable relationsship more or less likely to have sexual problems than diabetics living alone?)
These days, with the internet and the loads and loads of knowledge that are just flowing freely around online, there really is no good reason why a diabetic shouldn’t know at least as much about his/her disease than his/her primary care physician does.
Jeg var i morges til regelmæssig kontrol/screening på øjenafdelingen ved Århus Sygehus. Det var jeg, fordi diabetespatienter har en markant øget risiko ifht. befolkningen som helhed for på sigt at udvikle synstab – diabetes er den hyppigste årsag til blindhed blandt erhvervsaktive danskere – og derfor er der nu de fleste steder (overalt?) i landet indført regelmæssig screening af diabetespatienter med henblik på at fange øjenforandringerne, før de leder til synstab.
At få type 1 diabetes tidligt i livet udgør på langt sigt en ganske alvorlig risiko for at udvikle synstab: Ved en undersøgelse af patienter fra Fyn fulgt gennem 35 år (!), fra 1973 til 2008, der havde fået konstateret diabetes mellitus, type 1, havde kun 3% af de 255 overlevende diabetikere ingen retinopati ved undersøgelsens afslutning – hvilket naturligvis sagt på en anden måde vil sige, at 97% af patienterne på det tidspunkt havde diabetiske øjenforandringer. Over halvdelen (52%) havde i undersøgelsesperioden udviklet hvad der i undersøgelsens terminologi kaldes “synstruende retinopati”, hvilket betyder, at de på et tidspunkt i perioden havde haft så svære synstruende komplikationer i øjnene, at de blev laserbehandlet på mindst et øje. I perioden fra 1981 til 2008 blev 7.5% blinde. Jeg kan anbefale nysgerrige læsere at følge linket til undersøgelsen ovenfor; det har meget mere, og det forklarer også kort lidt om hvordan og hvorfor sygdommen udvikler sig.
Phd-studerende Kathrine Bonde Tilma arbejder lige nu på et projekt ved navn: Farmakologisk intervention mod forstyrrelser af nethindens blodgennemstrømning ved diabetisk øjensygdom. Hun mangler forsøgspersoner til at deltage i projektet, og kontaktede mig i løbet af min screening i dag, og spurgte om jeg ønskede at deltage, såfremt screeningsresultaterne gav anledning til at betragte mig som et potentielt interessant datapunkt (ikke lige med de ord, men…). Ved tidligere screeninger har der ingen forandringer været at se på mine øjne (endnu), og hvis det også gælder denne gang – hvad jeg selvfølgelig håber på – vil jeg ikke være interessant at inddrage i projektet. Jeg gav dog udtryk for, at jeg i udgangspunktet godt kunne tænke mig at deltage, hvis der var mulighed derfor.
Forskningsprojektet indebærer kun nogle for mig ret få, begrænsede risici – nej, jeg har ikke tænkt mig at beskrive hele forløbet i detaljer her – men også kun en meget lille potentiel upside. Alligevel vil jeg sige ja tak til at deltage, hvis jeg kan. Den bedste begrundelse jeg kan finde for min egen tilbøjelighed til at deltage, er at “jeg synes jeg bør”, men det “bør” vejer ret tungt. Hvis jeg forventede at få børn på et tidspunkt, ville det nok også være en væsentlig variabel i overvejelserne, eftersom diabetes har en arvelig komponent, men det gør jeg ikke.
Hvis jeg kommer med i undersøgelsen vil jeg naturligvis følge op på den her på bloggen, når resultaterne publiceres.
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