Not all chapters give me a lot of new insights – for example I know a lot more about the topic covered in the chapter about the Relationship Between Metabolic Control and Complications in Diabetes than what is covered in the book, and the ten-page chapter on The Diabetic Foot which I’ll soon read will not match the detailed coverage in Edmonds et al. – but anything else would be very surprising, and most chapters contain some stuff which I did not know. I understand the mechanisms driving microvascular complications better now than I did, but I’m still fuzzy on some of the details; like some of the genetics stuff in the first chapters that part of the book is very technical, and so I decided against covering that stuff in detail here. If you’re curious about that stuff, here’s a relevant link covering some of what the book has on that topic, in what seems from a brief skim to be a roughly similar amount of detail. To people who know nothing about this stuff (i.e., people who haven’t read my posts on related topics in the past…), diabetes in the long term causes damage to small and large blood vessels and may cause various forms of nerve damage (neuropathies) – here’s a brief and non-technical overview article. The connection between hyperglycemia – too high blood glucose – and small vessel disease is better established (and very well established at this point) than is the connection between hyperglycemia and large vessel disease, and although it may not sound too bad that small blood vessels are damaged, the consequences can be dire; long-term diabetes may among other things cause blindness and kidney failure. How precisely the blood vessels are damaged in diabetics was not very well understood for a very long time, but significant progress seems to have been made over the last couple of decades, and a ‘unifying theory’ of sorts – which brings together four separate mechanisms – seems to have been developed at this point. As mentioned you can have a look at ‘the relevant link’ above if you want to know more about the details.
Age is an important factor in treatment, as different age groups will respond in dissimilar manners to treatment and will face different problems (biological factors, behavioural factors), so the book has separate chapters on diabetes management in very young children, adolescents, etc. Though the level remains high throughout the book, I’d incidentally note that I don’t believe these chapters on special management issues in specific patient subgroups are that technical, and I think many diabetics would be able to benefit from reading those chapters. To a diabetic, much of the stuff covered in the treatment part will be well known although there’ll also be some new stuff. I was continually bothered throughout some of those chapters by the fact that when comparing treatment outcomes of patients on intensive treatment regimes with subcutaneous insulin injections and patients on insulin pumps, the obvious problems with selection into treatment in the latter group were not commented upon when comparing outcomes (though it must be said that one of the authors do comment on this aspect in a later chapter).
Below I’ve selected out some stuff from the middle 200 pages or so of the book. I’ve not completely ignored passages which may be a bit hard to understand for people without any knowledge of this disease – this is also a post written in order to make it easier for myself to remember what was covered in some of those chapters – however as mentioned above I’ve left out the really technical stuff. I have also bolded some key concepts and a few observations for the ‘lazy’ readers who can’t be bothered to read all of it, in order to make the post easier to navigate.
“Since its introduction, insulin has been life sustaining for patients with type 1 diabetes […] Although it is relativly inexpensive in the developed world, in many developing countries with limited health care resources, it is not routinely available (9). Indeed, children with type 1 diabetes in sub-Saharan Africa often do not live longer than 1 yr (10).” (I was wondering if this was an observation based on very old data (data access is a notorious problem when dealing with developing countries), but that seems not to be the case: “A child diagnosed with type 1 diabetes in sub-Saharan Africa has a life expectancy that varies between 7 months and 7 years, depending on the country” – link, original source is this article which I haven’t found an ungated copy of).
“[A] major risk of insulin therapy is weight gain. Insulin promotes fat storage in adipocytes and protein synthesis in muscles. […] [In the Diabetes Control and Complications Trial (DCCT)] the body mass index (BMI) increased approx 2 more units with intensive than with conventional treatment in both genders. In the whole DCCT cohort, the risk of becoming overweight was almost twofold greater with IT [intensive treatment – US] […] on average, adult subjects achieving a mean HbA1c of 7.2% gained 4.8 kg more during a 6-yr follow-up than their conventionally controlled counterparts” [my HbA1c is below 7.2% – US.]
“Exposure to a mean HbA1c of 11% for less than 3 yr yields the same rate of retinopathy as exposure to a HbA1c of 8% for 9 yr. The message is clear: The less time we allow a patient to be exposed to high levels of blood glucose, the better […] The adverse hyperglycemic effects on the eyes and kidneys exhibit a carryover effect manifested by a kind of “metabolic memory” displayed by these target organs. […] there is a momentum factor in retinopathy and nephropathy contributed to by the combination of glycemic level and time. The process of tissue damage builds up slowly, but in an accelerated fashion at higher HbA1c levels […], it decelerates slowly at lower HbA1c levels […], but also resumes its progression slowly after a period of time at lower HbA1c levels”
“It has long been recognized that treating and controlling diabetes is difficult. Diabetes is not an illness where a pill, an injection, or a particular diet is a cure. At best, there is hope to control it well. Optimal treatment demands dedication, motivation, energy, and knowledge. […] Dealing with these issues on a daily basis can be a psychological burden […] Thus, it is common for those with diabetes and/or close members of their families to have guilt, sorrow, and depression […] Although depression is not a complication of diabetes, it frequently is a consequence of the illness. The prevalence of depression in adults varies. Levels of diagnosable depression among those with diabetes are approximately three times the estimated prevalence in the population at large (8). Depression also might be more severe in people with diabetes and has especially adverse effects. Difficulty evolves in treatment when clinical depression contributes to poor self-care, worsened glycemia, and deepened depression (9).”
“Hyperglycemia before eating slows gastric emptying and results in a more prolonged glycemic response (8), whereas hypoglycemia speeds emptying and results in a faster, higher, and earlier peak response (9).” [I was not aware of this!]
“Persons with type 1 diabetes may attempt to substitute protein for carbohydrates to attenuate postprandial glucose response. A large cross-sectional study in type 1 diabetes found that protein intakes greater than 20% of total energy intake were associated with higher albumin excretions than <20% dietary protein (43). Concern over the role protein intake plays in renal function suggests that consuming more than 20% protein in the diet is unwise.” [As I’ve pointed out before (the second paper in the post), salt intake seems like a more obvious place to intervene – but protein intake is not irrelevant].
“Diabetes is less frequent in preschool children than in older ages. In a large survey in Europe, age-specific incidence was compared among 3 age groups in more than 3000 cases during 1989–1990 (1). Eighteen percent of the cases were observed in children younger than 4 yr, 34% between 5 and 9 yr, and 48% in children aged 10–14 yr. Similar results have been obtained in North America (2). [I got diagnosed at the age of 2 – US] […] A major characteristic of metabolic control in type 1 preschool children is the unstable glycemic control with its accompanying risk of severe hypoglycemia […] In young children, severe and recurrent hypoglycemias are of major concern because they may impair normal brain development. When tested during adolescence, patients who presented with early-onset diabetes and/or a history of severe hypoglycemia showed global or selective neuropsychological dysfunction such as impairment of visual–spatial skills, psychomotor efficiency, attention, or memory (28–32). As early as 2 yr after disease onset, evidence exists for mild neuropsychological dysfunction (33). Onset of diabetes early in life (before 5 yr of age) predicted negative changes in neuropsychological performances over the first 2 yr of the disease (34).” [I’ve talked about this aspect of the disease before. Below’s a bit more on this stuff:]
“The long-term risk of recurrent severe episodes of hypoglycemia, involving coma or convulsions, on the development of permanent cognitive impairment remains controversial. […] There continue to be concerns about young children with type 1 diabetes, particularly those diagnosed less than 5 yr of age in whom defects in tests of cognitive function have consistently been found (126–131). […] It is likely that the developing brain is more susceptible to damage during episodes of metabolic derangement. Deficiencies have been found in a number of cognitive domains but especially those that are more likely to be those originating in the frontal lobe. Not all of these studies have found a link with prior episodes of severe hypoglycemia, although more recent investigations have shown links between hypoglycemia and cognitive impairment.”
“The pubertal growth spurt is induced by sex hormones in both boys and girls, leading to increased amplitude of growth hormone (GH) pulses, and a rise in circulating insulinlike growth factor-1 (IGF-1) (26). Both the sex hormones and GH contribute to insulin resistance (27) and worsening glycemic control (28) […] Insulin also plays an important anabolic role during puberty. Failure to adequately increase insulin doses during this period has adverse effects on diabetic control, leading to the impairment of growth and pubertal development […] The GH/IGF axis, which plays a central role in the growth acceleration of puberty, can be significantly disordered in the diabetic adolescent with poor diabetic control, contributing to both growth impairment and greater insulin resistance (30).” [Incidentally both my brothers are higher than I am, though I can’t be absolutely certain this has anything to do with my diabetes… – US] […]
“In a retrospective, longitudinal study of 118 adolescent 18-yr-olds with type 1 diabetes, studied at three-monthly intervals between 8 and 18 yr, we found a significant deterioration in metabolic control throughout the period of adolescence (52). […] Quality of life may also deteriorate during this time (53) […] Adolescents with diabetes, unlike younger children, were reported by their parents as having poorer emotional and behavioral outcomes and poorer self-esteem outcomes than the nondiabetic adolescents.”
“Few diabetic women lived to childbearing age before the advent of insulin in 1922. Until then, less than 100 pregnancies were reported in diabetic women and most likely these women had type 2 and not type 1 diabetes. Even with this assumption, these cases of diabetes and pregnancy were associated with a greater than 90% infant mortality rate and a 30% maternal mortality rate (1,2). As late as 1980, physicians were still counseling diabetic women to avoid pregnancy (3). […] There is an increased prevalence of congenital anomalies and spontaneous abortions in diabetic women who are in poor glycemic control during the period of fetal organogenesis, which is nearly complete by 7 wk postconception. A woman may not even know she is pregnant at this time. It is for this reason that prepregnancy counseling and planning is essential in diabetic women of childbearing age. Because organogenesis is complete so early on, if a woman presents to her health care team and announces that she has missed her period by only a few days, there is still a chance to prevent cardiac anomalies by swiftly normalizing the glucose levels. However, potential neural tube defects are probably already established by the time the menstrual period is missed. […] HbA1c values early in pregnancy are correlated with the rates of spontaneous abortion and major congenital malformations […] normalizing blood glucose concentrations before and early in pregnancy can reduce the risks of spontaneous abortion and congenital malformations nearly to that of the general population (6–12).”
“The life expectancy for patients with diabetic end-stage renal failure is only 3 or 4 yr.” [I was wondering if perhaps this statement was based on old data (you never know), so I had a look around. It doesn’t seem to be – this is really how ‘well’ people do today. See e.g. the figure on page 6 of this study published earlier this year – half of the diabetics with end-stage renal failure were dead after 3 years, and only about a third survived 5 years. Yes, sometimes people get lucky – they ‘get a transplant and live for decades’. But most diabetics don’t; they just die, quite fast.]
“Although all cells in a person with diabetes are exposed to elevated levels of plasma glucose, hyperglycemic damage is limited to those cell types, such as endothelial cells, that develop intracellular hyperglycemia. Endothelial cells develop intracellular hyperglycemia because, unlike most other cells, they are unable to downregulate glucose transport when exposed to extracellular hyperglycemia […] vascular smooth muscle cells, which are not damaged by hyperglycemia, show an inverse relationship between extracellular glucose concentration and subsequent rate of glucose transport […] In contrast, vascular endothelial cells show no significant change in subsequent rate of glucose transport after exposure to elevated glucose concentrations”
“Diabetic ketoacidosis (DKA) is a potentially life-threatening medical emergency that reflects a state of metabolic decompensation in patients with insulin-dependent diabetes mellitus (IDDM) […] At least 25% of patients with new-onset diabetes mellitus type 1, especially children, will present in ketoacidosis (1–6). […] The cardinal hormonal alteration that triggers the metabolic decompensation of DKA is insulin deficiency accompanied by an excess of glucagon and the stress hormones epinephrine, norepinephrine, cortisol, and growth hormone (2,3,6). Insulin stimulates anabolic processes in liver, muscle, and adipose tissues and thereby permits glucose utilization and storage of the energy as glycogen, protein, and fat […] Concurrent with these anabolic actions, insulin inhibits catabolic processes such as glycogenolysis, gluconeogenesis, proteolysis, lipolysis, and ketogenesis. Insulin deficiency curtails glucose utilization by insulin-sensitive tissues, disinhibits lipolysis in adipose tissue, and enhances protein breakdown in muscle. Glucagon acting unopposed by insulin causes increased glycogenolysis, gluconeogenesis, and ketogenesis. Although insulin and glucagon may be considered as the primary hormones responsible for the development of DKA, increased levels of the stress hormones epinephrine, norepinephrine, cortisol, and growth hormone play critical auxiliary roles. Epinephrine and norepinephrine activate glycogenolysis, gluconeogenesis, and lipolysis and inhibit insulin release by the pancreas. Cortisol elevates blood glucose concentration by decreasing glucose utilization in muscle and by stimulating gluconeogenesis. Growth hormone increases lipolysis and impairs insulin’s action on muscle. The catabolic and metabolic effects of each of these counterregulatory hormones are accentuated during insulin deficiency […] the effects are synergistic and not merely additive. Even in normal persons, high concentrations of these counterregulatory hormones can induce hyperglycemia and ketonemia” (see also this and this – US)
“The classical patient with DKA is characterized by dehydration, acidosis with hyperventilation, with varying degrees of cerebral obtundation, and peripheral circulatory compromise […] the most common precipitating factors following initial presentation are omission of insulin, infection, and, in adults, typical or atypical myocardial infarction (1,7). […] In children, the major complication of concern during treatment for DKA is cerebral edema and related intracerebral complications […] [children are] at a disproportionately higher risk for developing clinical cerebral edema as compared to adults with DKA. Clinically relevant cerebral edema is estimated to occur in 0.7–1.0% of episodes of diabetic ketoacidosis in children (26–28). […] Once clinically obvious, cerebral edema is associated with a mortality of about 70% and only 7–14% of these patients escape permanent impairment of neurological function (31).”
i. “They tell us that Suicide is the greatest piece of Cowardice… That Suicide is wrong; when it is quite obvious that there is nothing in this world to which every man has a more unassailable title than to his own life and person.” (Arthur Schopenhauer)
ii. “When I am dead I would rather people thought me better than I was instead of worse; but if they think me worse, I cannot help it and, if it matters at all, it will matter more to them than to me.” (Samuel Butler) [I’d personally prefer a third option: That people didn’t think of me/about me at all after my death. If I were completely forgotten right after my death, rather than 50 or 100 years later as is usually the case, my death would cause other people still alive
much less harm and grief.]
iii. “To me it seems that those who are happy in this world are better and more lovable people than those who are not.” (-ll-)
iv. “The inert mind is a greater danger than the inert body, for it overlays and stifles the desire to live.” (Robertson Davies)
v. “No snowflake in an avalanche ever feels responsible.” (Stanisław Lec)
vi. “Do not put your faith in what statistics say until you have carefully considered what they do not say” (William Watt)
vii. “Most people get a fair amount of fun out of their lives, but on balance life is suffering, and only the very young or the very foolish imagine otherwise.” (George Orwell)
viii. “One of the main reasons that it is so easy to march men off to war is that each of them feels sorry for the man next to him who will die.” (Ernest Becker)
ix. “Wisdom comes from experience. Experience is often a result of lack of wisdom.” (Terry Pratchett)
x. “Wisdom doesn’t necessarily come with age. Sometimes age just shows up all by itself.” (Tom Wilson)
xi. “I like work. It fascinates me. I can sit and look at it for hours.” (Jerome K. Jerome)
xii. “It is impossible to enjoy idling thoroughly unless one has plenty of work to do. There is no fun in doing nothing when you have nothing to do. Wasting time is merely an occupation then, and a most exhausting one. Idleness, like kisses, to be sweet must be stolen.” (-ll-)
xiii. “There’s nothing worse than being an ageing young person.” (Richard Pryor)
xiv. “Whenever two people meet there are six present. There is the man as he sees himself, each as the other person sees him, and each man as he really is.” (William James)
xv. “The real persuaders are our appetites, our fears and, above all, our vanity. The skillful propagandist stirs and coaches these internal persuaders.” (Eric Hoffer)
xvi. “It is doubtful if the oppressed ever fight for freedom. They fight for pride and power — power to oppress others. The oppressed want above all to imitate their oppressors; they want to retaliate.” (-ll-)
xvii. “A man is likely to mind his own business when it is worth minding. When it is not, he takes his mind off his own meaningless affairs by minding other people’s business.” (-ll-)
xviii. “We can be absolutely certain only about things we do not understand. A doctrine that is understood is shorn of its strength.” (-ll-)
xix. “The awareness of their individual blemishes and shortcomings inclines the frustrated to detect ill will and meanness in their fellow men. Self-contempt, however vague, sharpens our eyes for the imperfections of others. We usually strive to reveal in others the blemishes we hide in ourselves.” (-ll-)
xx. “To believe that if we could have but this or that we would be happy is to suppress the realization that the cause of our unhappiness is in our inadequate and blemished selves. Excessive desire is thus a means of suppressing our sense of worthlessness.” (-ll-)
A few lectures from Gresham College:
An interesting lecture on symmetry patterns and symmetry breaking. A lot of the discussion of the relevant principles takes animal skin patterns and -movement patterns as the starting point for the analysis, leading to interesting quotes/observations like these: “Theorem: A spotted animal can have a striped tail, but a striped animal cannot have a spotted tail”, and “…but it can’t result in a horse, because a horse is not spherically symmetric”.
He also talks about e.g. snowflakes and sand dunes and this does not feel like a theoretical lecture at all – he’s sort of employing an applied maths approach to this topic which I like. Despite the fact that it’s basically a mathematics lecture it’s quite easy to follow and I enjoyed watching it.
He takes a long time to get started and he doesn’t actually ever say much about the non-Euclidian stuff (he never even explicitly distinguishes hyperbolic geometry from elliptic geometry using those terms). He’s also not completely precise in his language during the entire lecture; at one point he emphasizes the fact that three specific choices used in a proof were ‘mutually exclusive’ as though that was what was the key, even though what’s actually critical is that they were also collectively exhaustive – a point he fails to mention (and I’d assume it would be easy for a viewer not reasonably well-versed in mathematics to mix up these distinctions if they were not already familiar with the concepts). But maybe you’ll find it interesting anyway. It wasn’t a particularly bad lecture, I’d just expected a little more. I know where to go look if one wants a more complete picture of the things briefly touched upon in this lecture and I’ve looked at that stuff before, but I’m certainly not going to read Penrose again any time soon – that stuff’s way too much work considering the benefits of knowing that stuff in details (if I’m even theoretically able to obtain knowledge of the details – some of that stuff is really hard).
It’s been a while since I read stuff from this book, but I’m behind on the blogging so I decided to have a second look at some of that stuff. I never really got to talking much about chapter 14 (about liver disease) in my last post, and since then I’ve also read about disorders of the exocrine pancreas (chapter 15), renal disease (chapter 16), disorders of the parathyroids and calcium metabolism (chapter 17), and disorders of the endocrine pancreas (chapter 18). In this post I’ll limit my coverage to liver disease – it’s a fairly long chapter and these posts take quite a bit of time.
Before I start out with the main coverage, I should note that the one main take-away from this chapter is that the liver does a huge amount of different stuff. There’s a reason we can’t live without this organ (or perhaps a better way to think about this is that there are rather lots of reasons).
Anyway, on to the chapter coverage. The chapter starts out with a brief overview of how liver disease presents and some key concepts. Overview of the structure and function of the liver (anatomical- and histological features etc.) then follows, description of blood flow to the organ, and a description of the various functions the liver has (energy metabolism; protein synthesis; solubilization, transport and storage functions; protective and clearance functions). Then an overview of liver disease follows – what goes wrong, how it manifests, etc. Given how many functions the liver has, liver disease can cause a lot of problems with a lot of different things, and I decided to cover this part in a bit of detail below. First of all, problems with the liver can mess up all kinds of metabolic processes: Altered carbohydrate metabolism secondary to liver disease may cause hypo- or hyperglycemia, altered lipid metabolism may cause fat accumulation within the liver or elsewhere in the body, whereas altered protein metabolism may cause altered mental status and even coma (hepatic encephalopathy). Bile (a fluid produced by the liver to help with digestion) secretion failure, termed cholestasis, may cause various forms of malabsorption and deficiency states – classical signs of liver disease, jaundice and icterus (yellow discoloration of sclera (the whites of the eyes) and skin), are both caused by build-up of bilirubin caused by cholestasis. Most people are aware of the liver’s role in drug metabolism, and of course a failing liver will not clear drugs as well as a healthy liver will; a problematic aspect in particular here is that impaired clearance may make individuals abnormally sensitive to the toxic effects of drugs. Incidentally the liver clears drugs and other things through various phases, which means that different types of liver cells end up getting exposed to different types of compounds; the liver isn’t just a big clump of cells which tend to get harmed the same way by hepatotoxic substances. Rather what happens in cases of hepatotoxic exposures is that different liver cells are harmed by different compounds in foreseeable ways, so that direct poisons harm the first clearance zones hardest, whereas other hepatotoxic substances will harm cells ‘further down the line’ which are the ones that get exposed to the toxic metabolites generated earlier in the process – sometimes it’s not the stuff that goes in which is toxic, but rather the stuff the liver cells need to convert it into to get it out of the system. Anyway, aside from the stuff already mentioned the liver also has a role in storing various substances, which means that liver dysfunction may cause vitamin deficiency states. The liver produces proteins which have various functions throughout the body and when its function is impaired critical proteins may not be produced in the necessary quantities, causing problems such as hypoalbuminemia-related edema (fluid build-up in tissues). Clotting factors are also produced by the liver and lack of those may lead to various coagulopathic states (bleeding disorders). Altered hormone clearance in the liver may cause things like elevation of blood estrogens, which may cause physiological changes such as gynecomastia. Liver failure may cause the kidneys to retain salt and water as a defence mechanism, and so patients with severe liver disease may develop kidney failure as a result of these processes. Ascites, excess fluid build-up in the peritoneal cavity, may develop through a ‘complex and multifactorial’ process. A particularly awful type of bad breath called fetor hepaticus may develop in late-stage liver disease.
As you can probably tell from the comments above, all in all there are a lot of ways in which a bad liver can screw you over. It does a lot of good things, so a lot of things can go wrong.
After covering general aspects of liver disease, the pathophysiological aspects of a few specific liver diseases are covered in the last part of the chapter. This part deals with acute hepatitis, chronic hepatitis, and cirrhosis. Various specific disorders and disease processes may cause each of these (with huge variation in symptoms/presentation and severity of disease), so the extent to which specific disorders are dealt with in detail in this part of the chapter may be debatable – but it’s good stuff anyway. I decided not to cover the stuff in that part of the chapter in great detail but I do want to give a brief overview with some key points, and actually a pretty good big-picture short version of many of the relevant clinical distinctions is given in the beginning of the chapter:
“Although many different pathogenic agents and processes can affect the liver […], they are generally manifested in individual patients in a limited number of ways that can be assessed by evaluation of some key parameters. Liver disease can be acute or chronic; focal or diffuse; mild or severe; and reversible and irreversible. Most cases of acute liver disease (eg, due to viral hepatitis) are so mild that they never come to medical attention. […] The patient recovers without any lasting medical consequences. In other cases of acute liver injury, symptoms and signs are severe enough to call for medical attention. The entire range of liver functions may be affected or only a few […] Occasionally, viral and other causes of acute liver injury occur in an overwhelming manner with massive liver cell death. This syndrome of fulminant hepatic failure carries a high mortality rate, but if the patient survives, liver function returns to normal and there is no residual evidence of liver disease.
Liver injury may continue beyond the initial acute episode or may be recurrent (chronic hepatitis). In some cases of chronic hepatitis, liver function remains stable or the disease process ultimately resolves altogether. In other cases, there is progressive and irreversible deterioration of liver function.
Cirrhosis is ultimately the consequence of progressive liver injury. Cirrhosis can occur in a subset of cases of chronic hepatitis that do not resolve spontaneously or after repeated episodes of acute liver injury, as in the case of chronic alcoholism. In cirrhosis, the liver becomes hard, shrunken, and nodular and displays impaired function and diminished reserve due to a decreased amount of functioning liver tissue. More importantly, the physics of blood flow is altered such that blood in the hepatic portal vein is diverted around the liver rather than being filtered through the liver. This phenomenon, termed portal-to-systemic shunting, has profound effects on the function of various organ systems and sets the stage for certain devastating complications of liver disease […]
The consequences of liver disease can be either reversible or irreversible. Those arising directly from acute damage to the functional cells of the liver, most notably hepatocytes, without destruction of the liver’s capacity for regeneration, are generally reversible. Like many organs of the body, the liver normally has both a huge reserve capacity for the various biochemical reactions it carries out and the ability to regenerate fully differentiated cells and thereby recover completely from injury. Thus, only in the most fulminant cases or in end-stage disease are there insufficient residual hepatocytes to maintain minimal essential liver functions.”
Some related comments from the last half of the chapter:
Based on clinical, laboratory, and biopsy findings, chronic hepatitis is often divided into two classes: chronic persistent and chronic active hepatitis. Chronic persistent hepatitis is seldom progressive despite persistent biochemical abnormalities reflecting ongoing liver cell necrosis. The clinical course is relatively benign, often characterized by spontaneous resolution (eg, clearance of persistent viral infection). Chronic active (aggressive) hepatitis is typically progressive, often resulting ultimately in cirrhosis and its complications or liver failure and death.” […] The complications of chronic active hepatitis are those of progression to cirrhosis – variceal bleeding, encephalopathy, coagulopathy, hyperspleenism, and ascites. These are largely due to portal-to-systemic shunting rather than diminished hepatocyte reserve” […]
“Either type of chronic hepatitis can be caused by infection with several hepatitis viruses (eg, hepatitis B with or without hepatitis D superinfection and hepatitis C); a variety of drugs and poisons (eg, ethanol, isoniazid, acetaminophen), often in amounts insufficient to cause symptomatic acute hepatitis; genetic and metabolic disorders (eg, α1-antiprotease (α1-antitrypsin) deficiency, Wilson’s disease, and hemochromatosis); or immune-mediated injury of unknown origin. […] A specific cause can be determined for only 10-20% of patients. […]
“As with other presentations of liver disease, not all patients with cirrhosis develop life-threatening complications. Indeed, in nearly 40% of cases, cirrhosis is diagnosed at autopsy in patients who did not manifest obvious signs of end-stage liver disease.”
Share whatever you like – links, books, christmas present ideas (I’m planning on giving that whole thing a miss, but I’m not the only one reading the comments), …
My contributions to the discussion below:
i. Alcohol may not just be bad for the fetuses that make it out of the birth canal:
“Of the 186 pregnancies, 131 resulted in delivery of a child, and 55 (30 percent) were spontaneously aborted. Of the abortions, 34 were detected only by urinary hCG before or at 6 completed gestational weeks. The 21 clinically recognized abortions occurred in the interval after 6 and by 15 completed gestational weeks.
A high intake of alcohol by women or their partners was associated with a higher frequency of spontaneous abortions than was a low intake (table 1). Women who experienced a spontaneous abortion were older and had, on average, longer menstrual cycles, a higher caffeine intake, and partners with a higher caffeine intake than did women who gave birth (table 1). No association was found between spontaneous abortion and the partner’s smoking habits, partner’s age, body mass index, and partner’s reproductive illnesses; contraception last used; education for both man and woman; or hours at work for both partners.
The crude associations between female and male alcohol intakes and spontaneous abortion shown in figures 1 and 2 changed only slightly by adjustment for the confounders listed in table 2. Female alcohol intake was associated with a 2–3 times higher adjusted risk of spontaneous abortion compared with no intake, and male intake was associated with a 2–5 times increase in the adjusted risk. However, only the relative risks for male and female intakes of 10 or more drinks/week compared with no intake were statistically significant. We found a high correlation between male and female alcohol intakes. Additional adjustment for male intake revealed a lower risk of spontaneous abortion associated with female alcohol intake, whereas the higher risk associated with a high male alcohol intake changed only slightly following adjustment for female intake […] women in this study with a moderate or high alcohol intake [also] have an increased waiting time to pregnancy”
The quotes above are from Alcohol Consumption at the Time of Conception and Spontaneous Abortion, by Henriksen, Hjollund et al.
I should note that I don’t know enough about this stuff to comment intelligently on the findings. I’m planning to read Principles and Practice of Clinical Trial Medicine at some point in the not-too-distant future, and so I figured I ought to wait until I have had a go at that book to comment on this stuff. I wanted to add the link anyway though, in part so that I’d remember it in case it’ll be a while until I read Chin & Lee’s book.
iii. On a more personal note, Monday evening I beat an International Master for the first time in my life. It was in a one-minute bullet game (each player gets one minute to play the entire game) so it was not a particularly well played game, but I consider this to be a somewhat significant milestone still – IMs are really good chess players (‘An International Master is usually in the top 0.25% of all tournament players at the time he or she receives the title’ – from the wiki-link above). My opponent was Migchiel De Jong – here’s his Fide profile, here’s the game. There’s incidentally no doubt this was the guy I played – his full name is on his profile and his blitz rating was above 2600 when I played him (which is high – higher than some GMs on the site). It wasn’t a case of me getting outplayed but winning on time anyway – rather I had a mate in one in the game which he spotted after he’d made his move, and he resigned as a consequence of spotting the mate even though I missed it. When he resigned he had only 0.3 seconds left on his clock, so this may have been a contributing factor; if he’d not resigned he’d have lost on time. I had 3.6 seconds left which was of course the main reason why I didn’t spot the mate – I was too busy making moves in the time scramble in order not to lose on time to look for mates.. The time-trouble was incidentally also of course the reason why I was only up a piece when he resigned and why I did not take his queen when he blundered it a few moves earlier (bullet-chess can get pretty wild…).
Although it’s not like I haven’t read some stuff about my disease over the years, the amount of textbook reading on the topic I’ve done has so far been limited to just a couple of books (and none of these have really been ‘textbooks on type 1 diabetes’); most of the stuff I know I’ve learned from the scientific literature, e.g. Diabetes Care articles, Cochrane reviews and similar, and in general the books which have dealt with diabetes which I’ve read have not been all that concerned about the various distinctions one might choose to make between the somewhat heterogenous disorders all going under the common name of ‘diabetes’. In ‘random books’ I think it’s fair to say that ‘diabetes’ usually is best translated ‘type 2 diabetes’, and the specific aspects of that disease most interesting to many book authors on health and related stuff are precisely the aspects which are completely irrelevant to type 1’s (e.g. lifestyle stuff related to prevention and disease progression in type 2’s).
So I decided to read this book to get a more solid background. Which kind of book is it? Here’s a quote from the introduction:
“The aim of Type 1 Diabetes: Etiology and Treatment is to fuse […] contemporary investigational and practical issues and make them available to those involved in the research and practice of type 1 diabetes. This volume is not intended to be a comprehensive or exhaustive treatise on the subject of diabetes. As in many such endeavors, the pace of discovery often exceeds the ability to incorporate the latest knowledge into printed text. Nevertheless, we believe that this volume presents contemporary information on contemporary issues by recognized authorities in the field. We hope it stimulates thought and action in the research and care of patients with type 1 diabetes mellitus.”
In case you were wondering, “make them available to those involved in the research and practice of type 1 diabetes” = this is not a book for patients and it’s not an undergraduate textbook; it’s mainly a book for PhD students and endocrinologists. I’d say that even if you skip the introduction you probably don’t need to read 10 pages to realize that. This is the kind of book where I’ll read all the words and then see how much of it I actually understand, occasionally looking up stuff which I’m particularly interested in; but I’ll not put in the work to actually understand all the details of what’s covered in all the chapters of this book. I don’t care enough about stuff like this to be willing to spend the time and effort it takes to understand all the details. I’ve tried to be very careful about getting at least some ‘take-away’ message out of all chapters covered so that e.g. even though I’ll not understand all the various processes which get you to the finish line, at least I know what’s at the starting line and where you end up on the other side. You may think that I’m lazy and that I’m just (mentally) skipping the hard stuff, but although this is certainly true to some extent I should add that I consider it justified to say that even though I’m mentally skipping a few steps occasionally while reading this book I’m still engaged in ‘learning in depth’ – most of the stuff covered in this book is knowledge at a level way beyond what the average patient knows about genetics, immunology, metabolic pathways etc. I actually feel reasonably sure at this point that I’d not have continued reading past the first chapter of this book if I had not read McPhee et al. first (I haven’t read that entire book yet, but I’ve read a lot of stuff relevant to the coverage here).
It would be wrong of me to only talk about the downsides to the coverage in this post, i.e. that it’s a hard book for most people to read; the flip side of course is that there are a lot of interesting details here. The book is full of stuff I didn’t know I didn’t know. Fortunately enough for my coverage of the book here, despite the fact that the book in general is somewhat inaccessible not all chapters are equally ‘bad’, and so there is also occasionally some stuff in there which I believe to be reasonably accessible even to people who don’t know a whole lot about type 1 diabetes (though I may be making assumptions about people’s background knowledge here which are not warranted). Anyway I’ve tried to pick out some of those passages in my coverage below, and on the other hand I’ve tried very hard to stay clear of stuff most readers could not possibly be expected to understand. Do ask questions if some of the stuff is unclear to you. I’ve read roughly the first 180 pages. Note that not all the stuff below is from the book; I decided to add some comments of my own towards the end of the post. I decided to bold some of the stuff below so that even people who only skim the post may get something out of it.
“By 1990, two international groups [the EURODIAB Project and the DiaMond Project] working on the epidemiology of type 1 diabetes had been developed. […] Because of these two important projects, the descriptive epidemiology of type 1 diabetes has been mapped for most of the world, and we now know more about the international variation in the incidence of type 1 diabetes than practically any other chronic disease. Within a short 15-yr time period, the epidemiology of type 1 diabetes rose from a “black hole” of ignorance to one of the best characterized chronic diseases worldwide” […]
“The variation in the incidence of type 1 diabetes worldwide is greater than that observed for any other chronic disease in children. […] the global variation in risk is enormous. A child in Helsinki, Finland is almost 400 times more likely to develop diabetes than a child in Sichuan, China (8). To put this in perspective, consider the following example. If children in the United States had the same risk of developing type 1 diabetes as children in China, then instead of 13,000 newly diagnosed children each year, there would be only 56. In other words, over 99% of the annual new cases of type 1 diabetes in the United States would be avoided. […] Interestingly, the other epidemiologic features of type 1 diabetes are remarkably similar across populations, despite the enormous variation in disease risk (9). Incidence rates among males and females do not differ significantly, and the peak age at onset for both sexes occurs near the time of puberty. Thus, compared to all other risk factors, including human leukocyte antigen (HLA) haplotypes, viral infections, or the presence of autoantibodies, the place where a child lives is the most potent determinant of type 1 diabetes risk, excluding genetic/racial differences. If we knew what was causing the geographic patterns of type 1 diabetes, we would be well on our way to preventing the disease.” […]
“Temporal trends in chronic disease incidence rates are almost certainly environmentally induced. If one observes a 50% increase in the incidence of a disorder over 20 yr, it is most likely the result of changes in the environment because the gene pool cannot change that rapidly. Type 1 diabetes is a very dynamic disease. […] the incidence of type 1 diabetes is rising [and] these findings indicate that something in our environment is changing to trigger a disease response. […] The data […] clearly indicate that environmental factors are involved in the etiology of type 1 diabetes. With the exception of a possible role for viruses and infant nutrition, the specific environmental determinants that initiate or precipitate the onset of type 1 diabetes remain unclear. Type 1 diabetes is also, in large part, genetically determined” [here’s a relevant link, I won’t go into the details here although they spend a lot of pages talking about that stuff in the book]
“Evidence that type 1 diabetes is an autoimmune disorder is based on the presence of lymphocytic infiltrates of the pancreas at the onset of the diseases (37), as well as the occurrence of autoantibodies to islet cell antigens (ICAs), tyrosine phosphatase IA-2 (IA-2), glutamic acid decarboxylase (GAD), and insulin autoantibodies (IAA) (38,39). The presence of these autoantibodies indicates that tissue damage has likely been initiated by other etiologic agents. Thus, they represent important preclinical markers rather than risk factors for the disease. […] most type 1 diabetes cases have β-cell autoantibodies at disease onset, [however] not all autoantibody positive individuals develop the disease. […] first-degree relatives who are positive for multiple autoantibodies appear to be at very high risk for developing type 1 diabetes. […] about 90% of individuals who develop type 1 diabetes have a negative family history of the disease.”
“The autoimmune response in type 1 diabetes is […] similar to most other organ-specific autoimmune disorders in that both T-cells and autoantibody-producing B-cells are involved in the immune abnormalities associated with, as well as predicting, the disease (24). The molecular biology of β-cell destruction is therefore both diverse and complicated and the detailed mechanisms are yet poorly understood. […] At the time of clinical diagnosis of type 1 diabetes, about 80% of the β-cells have been specifically destroyed.”
“We currently know that for individuals with two HLA-DQ susceptibility haplotypes, the cumulative risk of type 1 diabetes in the general Caucasian population is approximately 5% (25). However, it may range from 0.1% to >90%, depending on one’s risk factor profile, which includes age, ethnic, familial, genetic, environmental, and autoimmune determinants.” […] Diabetogenic alleles are not fully penetrant” […] There is no simple “rule” for diabetes risk […] the position of provisional loci found in T1DM colocalize or overlap with loci found in different autoimmune/inflammatory diseases […] This is consistent with the hypothesis that, like the MHC, some of these provisional loci may involve common susceptibility genes or biochemical pathways that are central to normal immune function.”
“At present, the prediction of type 1 diabetes is not a major clinical issue outside of trials for diabetes prevention. Patients, especially children, usually present acutely with diabetes with a dramatic history of polyuria, polydipsia, and weight loss. Despite what in retrospect is almost always a clear-cut clinical history of diabetes, a significant number of children have a delay in diagnosis, which increases the risk of severe metabolic decompensation with diabetic ketoacidosis (DKA), cerebral edema, and death. […] Overall in the United States, DKA occurs in 25–50% of children with new-onset diabetes, and symptomatic cerebral edema occurs in approx 1% of DKA episodes. Of those patients with clinically apparent cerebral edema, between 40% and 90% die (1). […] In the United States […] it is rare to find individuals presenting with diabetes with normal HbA1c [an indicator of average blood glucose over the last 3 months or so – US] and it is likely that the great majority have had hyperglycemia for months prior to diagnosis.”
“Diabetes mellitus is classified based on clinical criteria into type 1 and type 2 diabetes (98). Recently, a growing number of monogenic diabetes disorders have been identified (98). Type 1 diabetes develops acutely. Ketoacidosis and coma develop unless insulin is administered. Type 2 diabetes develops mostly as a result of insulin resistance associated with obesity and β-cell dysfunction and occurs insidiously, and most patients are successfully controlled by diet, exercise, or oral hypoglycemic agents. […] the overall autoantibody frequency in type 2 patients varies between 6% and 10% (105). However, the positive predictive value that a GAD65Ab positive type 2 diabetes patient [that is, a type 2 diabetic with a specific genotype] will be treated with insulin within 5 yr is 100% […] Diabetes will appear as a function of loss of β-cell mass and loss of β-cell function. Different clinical phenotypes may develop, dependent on the combination of loss of β-cell mass and loss of function. […] A different severity of inflammation may lead to variable degree of β-cell inhibition and resulting hyperglycemia […] the degree of insulin resistance is also critical (99). Some subjects may encounter a severe loss of β-cells but, despite this, may not develop diabetes because of their high insulin sensitivity […] Other subjects may develop diabetes at modest β-cell loss because they are highly insulin resistant. Therefore, it is not surprising that type 1 diabetes or autoimmune diabetes is associated with a large number of different phenotypes […] To complicate the heterogeneity of autoimmune diabetes even further, it has also been found that patients with diabetes may develop GAD65 autoantibodies after the clinical diagnosis […] In contrast to […] patients masquerading as type 2 diabetic patients [because of slow onset of disease], an acute onset of type 1 diabetes is also reported (113). These patients have lower glycosylated hemoglobin values, diminished urinary excretion of C peptide, a more severe metabolic disorder with ketoacidosis, as well as higher serum pancreatic enzyme concentrations, compared to type 1 patients with a less dramatic onset […]
“All vertebrates use insulin-producing pancreatic β-cells to achieve fuel homeostasis (1). These cells are able to measure the nutrient levels of the blood on a moment-to-moment basis and secrete insulin at rates that are exactly appropriate for the maintenance of optimal fuel levels. Therefore, the levels of circulating nutrients such as glucose, fatty acids, and amino acids are precisely controlled in mammals during fasting and feeding alike. The role of the pancreatic β-cells in fuel homeostasis is thus analogous to that of the thermostat in heating and cooling systems (2,3).” [This sounds simple enough. However it gets ‘not simple’ very fast.]
“Hypoglycemia is the limiting factor in the glycemic management of diabetes because it generally precludes maintenance of euglycemia [normal blood glucose levels, US]. […] Were it not for the potentially devastating effects of hypoglycemia, particularly on the brain, glycemic control would be rather easy to achieve. Administration of enough insulin (or any effective medication) to lower plasma glucose concentrations to or below the nondiabetic range would eliminate the symptoms of hyperglycemia, prevent diabetic ketoacidosis and the nonketotic hyperosmolar syndrome, almost assuredly prevent retinopathy, nephropathy, and neuropathy, and likely reduce atherosclerotic risk. However, the devastating effects of hypoglycemia are real and the glycemic management of diabetes is therefore complex.” [much of chapter 7, from which the above and the following quotes originate, covers stuff I’ve covered before e.g. in this post, but there was some new stuff in that chapter as well and I actually think of this as the best of the chapters I’ve read so far]
“Iatrogenic hypoglycemia is the result of the interplay of therapeutic insulin excess and compromised physiological and behavioral defenses against falling plasma glucose concentrations in T1DM […] Glucose is an obligate metabolic fuel for the brain under physiological conditions (4). (The brain can utilize other circulating substrates, including ketones such as β- hydroxybutyrate, but the blood levels of these seldom rise high enough for them to enter the brain in quantity and thus partially replace glucose, except during prolonged fasting.) Because of its unique dependence on glucose oxidation as an energy source and because it cannot synthesize glucose or store more than a few minute’s supply as glycogen, the brain requires a continuous supply of glucose from the circulation. At normal plasma glucose concentrations the rate of glucose transporter (GLUT-1) mediated blood-to-brain glucose transport down a concentration gradient exceeds that of brain glucose metabolism. However, when arterial glucose concentrations fall below the physiological range blood-to-brain glucose transport falls and ultimately becomes limiting to brain glucose metabolism and thus its functions and even its survival. Given the immediate survival value of maintenance of the plasma glucose concentration, it is not surprising that physiological mechanisms that very effectively prevent or rapidly correct hypoglycemia have evolved.”
I was considering covering these mechanisms in detail as well, but I reconsidered and decided to cut it short. However a few remarks should be included on this topic. One key point here is that one of the important reasons why diabetics are prone to hypoglycemia is that most of the normal physiological defence mechanisms against hypoglycemia are basically destroyed in diabetics. The first step in the body’s correction of low blood glucose is reduction of insulin production. This takes place way before symptoms ever occur in normal people. Type 1 diabetics who’ve taken insulin for a while don’t produce insulin on their own, so their body can’t regulate/lower insulin production – it’s already at zero. So step one in the process is deactivated. The second step in the natural process to reverse hypoglycemia involves increased glucagon secretion; glucagon is a hormone which tells the liver to convert its stores of glucogen (a type of sugar) into glucose and release them into the bloodstream. The authors note that although glucagon responses to other stimuli remain mostly intact in diabetics, the response to hypoglycemia is destroyed, for reasons not well known. So the first two defence mechanisms against hypoglycemia are completely out of the window in diabetics. The main one left is increased epinephrine secretion. Normally this one only sets in after the first two other responses have failed, but a very important point is that the set point for when this mechanism sets in depends on how often the diabetic is hypoglycemic; if hypoglycemia is common, the body will start tolerating lower blood glucose levels without initiating the remaining counterregulatory mechanism (there are a few other mechanisms at play, but they basically only apply to long-term hypoglycemia and will not play any significant role in a diabetic with acute hypoglycemia). The epinephrine response will still be initiated eventually, but the blood glucose level needed to initiate the process will be downregulated over time if hypoglycemic episodes occur often, which is problematic for reasons explained below. An important observation from the book regarding this counterregulatory mechanism:
“The development of an attenuated epinephrine response to falling glucose levels — loss of the third defense against hypoglycemia — is a critical pathophysiological event. Patients with T1DM who have combined deficiencies of their glucagon and epinephrine responses have been shown in prospective studies to suffer severe hypoglycemia at rates 25-fold (45) or more (46) higher than those with absent glucagon but intact epinephrine responses during aggressive glycemic therapy.”
The main reason things tend to go bad in these cases is presumably that if the epinephrine response is lost, the first manifestation of hypoglycemia is neuroglycopenia; the diabetic learns that she has a low blood glucose only when her brain stops working properly. This makes engaging in the correct behavioural responses (ingestion of glucose) problematic.
The concepts of hypoglycemia unawareness and what’s termed hypoglycemia-associated autonomic failure are closely related and important concepts to be familiar with:
“The concept of hypoglycemia-associated autonomic failure in T1DM […] posits that (1) periods of relative or absolute therapeutic insulin excess in the setting of absent glucagon responses lead to episodes of hypoglycemia, (2) these episodes, in turn, cause reduced autonomic (including adrenomedullary epinephrine) responses to falling glucose concentrations on subsequent occasions, and (3) these reduced autonomic responses result in both reduced symptoms of, and therefore the behavioral response to, developing hypoglycemia (i.e., hypoglycemia unawareness) and — because epinephrine responses are reduced in the setting of absent glucagon responses — impaired physiological defenses against developing hypoglycemia (i.e., defective glucose counterregulation). Thus, a vicious cycle of recurrent hypoglycemia is created and perpetuated.”
A few more concluding remarks from the chapter:
“hypoglycemia risk reduction requires consideration of both the conventional risk factors that lead to episodes of absolute or relative insulin excess — insulin (or other drug) dose, timing, and type, patterns of food ingestion and of exercise, interactions with alcohol or other drugs, and altered sensitivity to or clearance of insulin — and the risk factors for compromised glucose counterregulation that impair physiological and behavioral defenses against developing hypoglycemia […] The underlying principle is that iatrogenic hypoglycemia is the result of the interplay of insulin excess and compromised glucose counterregulation rather than insulin excess alone.”
I was well aware that diabetics can’t regulate insulin production (of course) and that this is a problem in terms of counter-regulation which makes hypoglycemia more likely, but I had no idea that ‘normal people’ had other natural counter-regulatory mechanisms which are also impacted by diabetes (to be clear, I was familiar with the concept of hypoglycemia unawareness but I’d never read about it in detail and the glycagon-response deactivation in diabetics I was not aware of. I knew that injections of glucagon is a treatment option in case of severe hypoglycemia – I’ve had such injections a few times, though fortunately not within the last decade – but I didn’t know that ‘normal people’ naturally secrete this stuff on their own if/when their blood glucose drops). In case you were wondering how to break the cycle:
“In a patient with hypoglycemia unawareness, a 2- to 3-wk period of scrupulous avoidance of iatrogenic hypoglycemia is advisable”.
Basically the idea is to avoid hypoglycemias for a while in order to change the threshold where the epinephrine response kicks in. Of course one shouldn’t change it too much in the other direction; poorly regulated diabetics tend to have thresholds higher than normal, so that they get symptoms of hypoglycemia even when their blood glucose is within the normal range. Something like that of course makes it harder for those individuals to achieve the therapeutic goals of reasonably low Hba-1c’s. I was wondering if I should mention this or not because it might get confusing but I decided to anyway; it should be noted that hypoglycemia-associated autonomic failure is a different form of nervous system dysregulation in diabetics than the one that takes place in long-term diabetics who develop diabetic autonomic neuropathy (DAN). Hypoglycemia-associated autonomic failure is reversible, whereas DAN most of the time isn’t, and DAN may have a lot of unpleasant effects aside from ‘just’ hypoglycemia unawareness – while covering the relevant chapter in McPhee not too long ago I noted that DAN may affect the enteric nervous system and cause problems with peristalsis, but this is but one of many problems caused by autonomic dysregulation; see the link above for more on this stuff. It should be noted that the authors in McPhee do not seem to be aware of the fact (at least they do not make it clear…) that not all hypoglycemia-unawareness in diabetics is related to DAN. On a different if related note it might be added that the autonomous nervous system is not the only part of the nervous system that is potentially affected by diabetes in the long run; for example sensorimotor polyneuropathy affecting the extremities is a far from uncommon complication.
I read the book yesterday.
It’s an easy book to read and most people who’ve read it seem to like it – it has a rating average of 4.04 on goodreads. I decided in the end to give it two stars. It’ll be the last popular science book of this type I’ll read in a while, and you should note that if I didn’t happen to feel sick and tired of popular science books at this point I might have given it a higher rating – I don’t really think it’s any worse than Miller’s The Mating Mind which I gave three stars, but the question remains if I ought to subtract a star from that one rather than give this one another star. The main problem with these books is that I at this point feel that I just don’t learn enough new stuff from them to justify reading them, and they often make me annoyed due to the authors’ relatively lax standards of evidence and imprecise language (compared to, say, the language of academic textbooks), both of which are more or less direct consequences of the format.
I think there’s generally in these types of books too much speculation and too little worry on part of the author about saying things which are not supported by the data. Funny enough, thinking back to the discussion I had with Miao when covering Miller I should note that Ridley also seemed to have trouble figuring out how large vocabularies people tend to have. But unlike Miller, Ridley didn’t even feel any need to source his hilariously wrong estimate (see below) and that’s not a point in his favour even though the estimate isn’t in any way critical to the coverage. There are interesting observations in the book, quite a few of them, but often it’s harder to trust the author than it ought to be because he also says things which are plain wrong in his book and occasionally it’s very hard to pinpoint the source of an interesting observation, or even figure out if a source exists, because whole paragraphs may be supported by one source which doesn’t necessarily cover all the material in the paragraph in question – there are no (authors X and Y, 20XX) references like in academic papers, only an occasional number and a source in the back of the book; and once you realize that he says unsourced things which are not true in the text, you start worrying about the existence of unsourced observations within the sourced paragraphs as well. Or at least I did. Of course the fact that a statement is sourced doesn’t necessarily mean it’s right, but it’s a better starting point than is the alternative. Another major problem is that there are a lot of sentences which would be improved greatly by probability indicators like ‘perhaps’, ‘it’s likely that’, and similar – this relates to the ‘imprecise language’ part above. There’s too little doubt, and he’s sometimes way too categorical in his statements and/or give a too simplified view of the problem at hand.
Stuff I’ve read which covers some of the same stuff as is covered in this book includes Miller, Bobbi Low, the first couple of chapters in Scarre, a few chapters from Majerus, and some of Dawkins’ work. I already knew about the sex-parasites thing because that idea has been covered elsewhere, though of course the book has more details on this stuff. Anyway I think it’s safe to say that if you’re reasonably well-informed there’ll be a lot of pages in this book covering stuff you already know.
I’ve focused mainly on the good stuff in the book below, but I didn’t think it was right to only include good stuff, so there are a few ‘bad quotes’ and related critical remarks here and there as well.
“Selection within the species is always going to be more important than selection between the species.” [The source given to this claim is ‘Humphrey 1983’. This is a good example of the ‘he’s too categorical’ – Always??? I wonder what the hundreds of species which went extinct in Lake Victoria following the introduction of the Nile Perch have to say about that? Or what about the Dodo? Important in what way and for whom?]
“If a population is small […] or the number of genes in the creature is very large, [Muller’s] ratchet has a severe effect on an asexual lineage. […] being sexual was a prerequisite for being big (and therefore few), or, conversely, sex is unnecessary if you stay small.”
“among mammals, the amount of recombinations bears no relation to the number of young, little relation to body size, and close relation to age at maturity. In other words long-lived, late-maturing animals do more genetic mixing regardless of their size or fecundity than short-lived, early-maturing animals.”
“the probability that a family of animals will become extinct does not depend on how long that family has already existed. In other words, species do not get better at surviving […] Their chances of extinction are random. […] The struggle for existence never gets easier. However well a species may adapt to its environment, it can never relax, because its competitors and its enemies are also adapting to their niches. Survival is a zero-sum game.”
“Sex, according to the Red Queen theory, has nothing to do with adapting to the inanimate world […] but is all about combating the enemy that fights back. Biologists have persistently overestimated the importance of physical causes of premature death rather than biological ones. […] The things that kill animals or prevent them from reproducing are only rarely physical factors. Far more often they are other creatures – parasites, predators and competitors. […] Parasites have a deadlier effect than predators for two reasons. One is that there are more of them. […] The second reason, which is the cause of the first, is that parasites are usually smaller than their hosts while predators are usually larger. This means that the parasites live shorter lives and pass through more generations in a given time than their hosts.” […] Parasites and their hosts are locked in a close evolutionary embrace. The more successful the parasite’s attack […] the more the host’s chances of survival will depend on whether it can invent a defence. The better the host defends, the more natural selection will promote the parasites that can overcome the defence. So the advantage will always be swinging from one to the other: the more dire the emergency for one, the better it will fight. […] the notion of a host-parasite arms race is one of the most basic and unavoidable consequences of evolution.”
“The advantage of sex [to fight parasites] can appear in a single generation. This is because whatever lock is common in one generation will produce among the parasites the key that fits it. So you can be sure that it is the very lock not to have a few generations later. For by then the key that fits it will be common. Rarity is at a premium. […] many of the most notoriously polymorphic genes, such as the blood groups, the histocompatibility antigens and the like, are the very genes that affect resistance to disease – the genes for locks. Moreover, some of these polymorphisms are astonishingly ancient. […] Some very powerful force is at work ensuring that most versions of each gene survive, and that no version changes very much. That force is almost certainly disease. […] most asexual plants are short-lived annuals. Long-lived trees face a particular problem, because their parasites have time to evolve to their genetic defences – to evolve. […] Disease might almost put a sort of limit on longevity: there is little point in living much longer than it takes your parasites to adapt to you.” […this last sentence sort of conveys an old idea which I’ve had before, but the framing is different and the framing is important. When thinking about this aspect in the past I’ve usually tended to think only about the selective pressures imposed by predators, rather than e.g. those of diseases, but of course the latter are likely to play a major role as well.]
“larger, more intelligent and more social animals are generally more flexible in their mating systems than smaller, stupid or more solitary ones.”
“A female human being does not have to share her sexual favours with many males to prevent infanticide, but she may have a good reason to share them with one well-chosen male apart from her husband. This is because her husband is, almost by definition, usually not the best male there is – else how would he have ended up married to her? His value is that he is monogamous and will therefore not divide his child-rearing efforts among several families. But why accept his genes? Why not have his parental care and some other male’s genes? […] the principle – marry a nice guy but have an affair with your boss, or marry a rich but ugly man and take a handsome lover – is not unknown among female human beings.” […] [According to findings by Robin Baker and Mark Bellis] the typical woman’s pattern of infidelity […] is exactly what you would expect to find if she were unconsciously trying to get pregnant by a lover, while not leaving a husband.” [I don’t really know to which extent one should trust these findings, however, as other findings by them described by Ridley simply can’t be true and to me indicate questionable methodology at best:] “In a block of flats in Liverpool, they found by genetic tests that less than four in every five people were the sons of their ostensible fathers. The rest were apparently fathered by somebody else. In case this was something to do with Liverpool, they did the same tests in southern England and got the same result.” [As I put it in the margin, ‘these numbers are way too high.’ See e.g. this post by Razib Khan.]
“Cuckoldry paranoia is deep-seated in men. […] Cuckoldry is an asymmetrical fate. A woman loses no genetic investment if her husband is unfaithful, but a man risks unwittingly raising a bastard. […] It is not that a woman need not mind about her husband’s infidelity: it might lead to him leaving her, or wasting his time and money on his mistress, or picking up a nasty disease. But it does imply that men are likely to mind even more about their wives’ infidelity than vice versa. History, and law, have long reflected just that.”
“There has been no genetic change since we were hunter-gatherers, but deep in the mind of modern man is a simple hunter-gatherer rule: strive to acquire power and use it to lure women who will bear heirs; strive to acquire wealth and use it to buy affairs with other men’s wives who will bear bastards.” [“There has been no genetic change since we were hunter-gatherers“ – did he actually just say that? You just can’t write stuff like that. Again, this is way too categorical – it’s just plain wrong. There are plenty of recent genetic changes to be found (see e.g. this), if you care to look for it. Also, on a different matter the ‘strive to acquire wealth’ part of human behaviour today may well somehow be related to things which took place in hunter-gatherer times, but a male decision rule to strive for wealth in order to have more babies sure as hell isn’t derived from hunter-gatherer times; as he himself points out in his book, “accumulation of wealth was not possible in hunter-gatherer societies” (this is a direct quote from the book). It’s as if he’s unable to connect the chunks of knowledge he has obtained, and although that may well occasionally be hard this is just borderline weird.]
“the evidence for the average male brain differing in certain ways from the average female brain is now all but undeniable. […] There is no a priori reason for assuming that men and women have identical minds and no amount of wishing it were so will make it so if it is not so. […] to assume the sexes are mentally identical in the face of evidence that they are not is just as unfair as to assume sexual difference in the face of evidence that they are the same. […] mankind may be the mammal with the greatest division of sexual labour, and the greatest of mental differences between the sexes.” [He starts out well in that chapter. But then the politically correct crap shows its ugly face anyway…] “I think it is easy and, given the evidence, rational to believe that the [mental] differences between the natures of men of different races are trivial, while the differences between the natures of men and women of the same race are considerable.” [Yeah, well… IQ data shows a similar pattern to the one in the link: Good luck finding gender differences as large as the racial differences. I remember a finding from a paper from a course I took last year on the economics of education; they found that the average SAT score of black college-educated in their (US) sample was about the same as the average SAT score of a white high school graduate. I can’t be bothered to find the link, but the link above tells a similar story; the differences are huge. Switch ‘sexes’ with ‘races’, ‘males’ an ‘females’/’men’ and ‘women’ with ‘blacks’ and whites’ in the sentences quoted above and see where you end up. We didn’t have as much data on that kind of stuff when Ridley wrote his book as we do now, but we did have data back then as well and given the observed differences Ridley cannot have had good reasons for holding the view that he does. I won’t go so far as to call him a hypocrite, but he should at the very least consider reading Clifford.]
“True, we learn a lot more than bats and cuckoos do. We learn mathematics and a vocabulary of ten thousand words, and what people’s characters are like.” [No source in the book. Of course there isn’t – this number is bullshit, it’s not even close. See also this discussion. On the one hand the fact that he didn’t even feel the need to source the estimate makes him look worse than Miller, but on the other hand this isn’t an estimate which is as critical to the book or the chapter as it was to Miller. In Ridley’s case it’s likely just a number he drew out of a hat, not caring enough about whether it was right or not to actually try to find out. Intellectual laziness is the problem, not the fact that the number is wrong.]
“As Horace Barlow of Cambridge University has pointed out, the things of which we are conscious are mostly the mental events that concern social actions: we remain unconscious of how we see, walk, hit a tennis ball or write a word. Like a military hierarchy, consciousness operates on a ‘need to know’ policy.”