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The Successful Diabetes Handbook For Type 2 Diabetes - Isbn:9781446620779

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  • Book Title: The Successful Diabetes Handbook for Type 2 Diabetes
  • ISBN 13: 9781446620779
  • ISBN 10: 1446620778
  • Author: Rosie Walker, Jill Rodgers
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  • Synopsis: Both hot and cold weather make lower blood glucose levels more likely, or may affect your normal activity levels Have ... to make your own adjustments to your doses, here are a few pointers: Adjust doses of the medications that directly ... Available from NHS Diabetes reports pages. http://www.diabetes.nhs.uk/ publications_and_resources/reports_and_guidance/ ... produce guidelines on all aspects of treating diabetes, including blood glucose monitoring, and also publish versions ...

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Handbook of Incretin-based Therapies in Type 2 Diabetes

Handbook of Incretin-based Therapies in Type 2 Diabetes Book Title Handbook of Incretin-based Therapies in Type 2 Diabetes Copyright 2016 DOI 10.1007/978-3-319-08982-9 Print ISBN 978-3-319-08981-2 Online ISBN 978-3-319-08982-9 Publisher Springer International Publishing Copyright Holder Springer International Publishing Switzerland Additional Links
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The Successful Diabetes Handbook for Type 2 Diabetes - ISBN:9781446620779

10 facts about diabetes

The number of people with diabetes has nearly quadrupled since 1980. Prevalence is increasing worldwide, particularly in low- and middle-income countries. The causes are complex, but the rise is due in part to increases in the number of people who are overweight, including an increase in obesity, and in a widespread lack of physical activity.

Diabetes of all types can lead to complications in many parts of the body and increase the risk of dying prematurely. In 2012 diabetes was the direct cause of 1.5 million deaths globally. A large proportion of diabetes and its complications can be prevented by a healthy diet, regular physical activity, maintaining a normal body weight and avoiding tobacco use.

In April 2016, WHO published the Global report on diabetes, which calls for action to reduce exposure to the known risk factors for type 2 diabetes and to improve access to and quality of care for people with all forms of diabetes.

Fact 1: About 422 million people worldwide have diabetes.

The prevalence of diabetes has been steadily increasing for the past 3 decades, mirroring an increase in the prevalence of obesity and overweight people. In particular, the prevalence of diabetes is growing most rapidly in low- and middle-income countries.

Fact 2: Diabetes is 1 of the leading causes of death in the world

In 2012 diabetes was the direct cause of 1.5 million deaths.

An additional 2.2 million deaths were caused in the same year by higher-than-optimal levels of blood glucose, through an increased risk of cardiovascular and other diseases. Even when blood glucose levels are not high enough to warrant a diagnosis of diabetes damage can occur to the body.The risk of cardiovascular disease rises as blood glucose levels rise.

Fact 3: There are 2 major forms of diabetes.

Type 1 diabetes is characterized by a lack of insulin production and type 2 diabetes results from the body's ineffective use of insulin. While type 2 diabetes is potentially preventable, the causes and risk factors for type 1 diabetes remain unknown, and prevention strategies have not yet been successful.

Fact 4: A third type of diabetes is gestational diabetes.

Gestational diabetes is characterized by hyperglycaemia, or raised blood sugar, with values above normal but below those diagnostic of diabetes, during pregnancy. Women with gestational diabetes are at an increased risk of complications during pregnancy and delivery. They and their children are also at increased risk of type 2 diabetes in the future.

Fact 5: Type 2 diabetes is much more common than type 1 diabetes.

Type 2 accounts for the majority of cases of diabetes worldwide. Higher waist circumference and higher body mass index (BMI) are associated with increased risk of type 2 diabetes, though the relationship may vary in different populations. Reports of type 2 diabetes in children – previously rare – have increased worldwide.

Fact 6: People with diabetes can live long and healthy lives when their diabetes is detected and well-managed.

A series of cost-effective interventions can help people diagnosed with diabetes manage their condition. These interventions include: blood glucose control through a combination of diet, physical activity and, if necessary, medication; control of blood pressure and lipids to reduce cardiovascular risk and other complications; and regular screening for damage to the eyes, kidneys and feet, to facilitate early treatment.

Fact 7: Early diagnosis and intervention is the starting point for living well with diabetes.

The longer a person lives with undiagnosed and untreated diabetes, the worse their health outcomes are likely to be. Basic technologies such as blood glucose measurement should be readily available in primary health-care settings.

WHO/ Q. Mattingly

Fact 8: The majority of diabetes deaths occur in low- and middle-income countries

In general, primary health-care practitioners in low-income countries do not have access to the basic technologies needed to help people with diabetes properly manage their disease. Access to essential medicines (including life-saving insulin) and technologies is limited in low- and middle-income countries.

Fact 9: Diabetes is an important cause of blindness, amputation and kidney failure

Diabetes of all types can lead to complications in many parts of the body and increase the overall risk of dying prematurely. Possible complications include heart attack, stroke, kidney failure, leg amputation (because of infected, non-healing foot ulcers), vision loss and nerve damage.

Fact 10: Type 2 diabetes can be prevented

Thirty minutes of moderate-intensity physical activity on most days and a healthy diet can drastically reduce the risk of developing type 2 diabetes.



Type 2 diabetes: Causes, symptoms, treatment and management

Diabetes health centre Type 2 diabetes

Type 2 diabetes is the most common type of diabetes. with around 3 million people in the UK diagnosed with the condition.

A person with type 2 diabetes has insulin resistance. meaning their pancreas doesn’t produce enough insulin or the body doesn't react properly to insulin.

Insulin is used by the body to manage glucose, or sugar. levels in the blood and to convert glucose into energy.

For some people, type 2 diabetes may be managed through diet and exercise. Other people may also need medication to manage blood sugar .

Risk factors for type 2 diabetes include being over 40, having a family history of diabetes. being of South Asian, African-Caribbean or Middle Eastern origin or being overweight or obese.

How type 2 diabetes affects the body

When glucose builds up in the blood instead of going into cells, the cells are not able to function properly. Other problems associated with the build-up of glucose in the blood include:

  • Dehydration . The build-up of sugar in the blood leads to excess glucose in the urine because the kidneys can’t deal with the high sugar levels. The sugar in the urine draws water with it, causing an increase in urination. When the kidneys lose the glucose through the urine, a large amount of water is also lost, causing dehydration.
  • Diabetic coma (hyperosmolar hyperglycaemic non-ketotic syndrome). When a person with type 2 diabetes becomes severely dehydrated and is not able to drink enough fluids to make up for the fluid losses, they may develop this life-threatening complication.
  • Damage to the body. Over time, the high glucose levels in the blood may damage the nerves and predispose a person to atherosclerosis (narrowing) of the arteries that can cause heart attack and stroke. and damage the eyes and kidneys.
Symptoms of type 2 diabetes

Type 2 diabetes can cause serious health complications. That's why it is very important to know how to spot type 2 diabetes symptoms. Even pre-diabetes can increase the chance of heart disease just like type 1 or type 2 diabetes. Talk to your doctor about preventative measures you can take now to reduce the chance of type 2 diabetes and heart disease .

The symptoms of type 2 diabetes due to high blood sugar may include:

  • Increased thirst
  • Increased hunger (especially after eating)
  • Dry mouth
  • Frequent urination
  • Unexplained weight loss (even though you are eating and feel hungry)
  • Fatigue (weak, tired feeling)
  • Blurred vision
  • Headaches
  • Loss of consciousness (rare)
  • Recurrent infections, including thrush infections

Seek medical advice if you have any type 2 diabetes symptoms or if you have further questions about type 2 diabetes. It’s important to get diabetes testing and start a treatment plan early to prevent serious diabetes complications .

Type 2 diabetes may not be diagnosed until health complications have occurred. Most often, with type 2 diabetes there are no diabetes symptoms or a very gradual development of the above symptoms of type 2 diabetes. In fact, about 600,000 people in the UK have type 2 diabetes but don't know they have it.

Other symptoms of type 2 diabetes may include:



Is type 2 diabetes reversible?

Yes. It is also possible to reverse the symptoms - it's a contentious statement to make, but it is, genuinely, possible. Not in all scenarios, but in many.

David Cavan, who ran a very successful diabetes management course in the UK and now head of policy at the IDF (International Diabetes Federation) has published a book The Step-by-Step Plan to Take Control of Type 2 Diabetes: Amazon.co.uk: Dr David Cavan: 9780091948252: Books which discusses how the type 2 'disease' process can be reversed. Understanding has changed a LOT in reference to type 2 diabetes.

  • Carb management (yes, everything you hold delicous may need to be reduced)
  • Diet: a LOT more focus on diet
  • Exercise
  • All vegetables and fruit are NOT made in the same vain
  • Testing for people with type 2 diabetes to understand the impact of food, diet, lifestyle, medication, etc on blood glucose levels
Simple? Maybe, but no-one said it was easy.

It makes sense. Type 2 diabetes = less insulin or not-efficient insulin. How to directly change that? Alter your mass, alter your intake, understand what affects your blood glucose, make better choices, reduce your A1c.

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More Answers Below. Related Questions

  • How can one in the U.S. or other Western countries find a good doctor for reversing type 2 diabetes?

  • What is the best diet and exercise plan for type 2 diabetics?

  • Can type 1 diabetes help promote the progression of type 2 diabetes?

  • What are the risk factors of type 2 diabetes?

  • How bad is smoking for a Type 2 diabetic?

  • What is the history of type 2 diabetes?

  • How do I treat type 2 diabetes naturally?

  • Can cinnamon reverse diabetes?

  • What are the latest techniques for treatment of type 2 diabetes?

  • Can you drink alcohol if you have Type 2 diabetes?

  • What is the best way to control/manage type-2 diabetes without medication?

  • What causes type 2 diabetes?

  • Can I take Omega 3-6-9 while I have diabetes type 2?

  • Should I ask to be tested for type 2 diabetes?

  • How do you know if you have type 2 diabetes?

    Kirnesh Pandey. M.D.;Consultant Diabetologist at Totall Diabetes Hormone Institute. Indore.

    Controllable but not reversible .

    Type 2 Diabetes is characterized by mainly two defects :
    1. Relative deficiency of insulin
    2. Decreased sensitivity of cells to the action of Insulin ( Insulin Resistance )

    Deficiency of insulin occurs due to decrease in the number and function of beta cells in pancreas. It is widely believed that by the time Diabetes sets in more than 50% of beta cells are already dead. Beta cells die naturally by a process called apoptotic cell death but this process is accelerated in those predisposed to Diabetes. Premature cell death occurs due to complex interplay between genetic predisposition and environmental factors.

    As yet there is no pragmatic way to revive dead beta cells so technically speaking Type 2 diabetes is not reversible. However glucose levels can be kept under good control from day one by proper use of drugs. insulin. diet and lifestyle modification

    Though beta cells can't be revived. the rate of its death can be slowed down. This concept is called Beta Cell Preservation and this is attempted by early insulin use and using certain class of drugs (like insulin sensitizers) etc.

    736 Views · View Upvotes · Not for Reproduction · Answer requested by 1 person

    Jonathan Brown. retired epidemiologist & computer disease modeler, winemaker, singer

    It depends. Type 1 diabetes, which is caused by the outright destruction of the insulin-producing beta cells in the pancreas via an auto-immune process, cannot be reversed with present technology, although scientists are working to perfect beta cell transplantation. But most people have Type 2 diabetes, which takes many forms, and can arise either from growing resistance to the action of insulin (most people, especially those aged 40-60), or from progressive failure of the beta cells due to aging or other causes. Diabetes due to insulin resistance often can be reversed if diagnosed early (before beta cell destruction) by intensive insulin therapy or a very low-calorie diet. This reversal probably will not last forever. Very obese persons with diabetes (obesity causes diabetes by increasing resistance to insulin), who qualify for bariatric survey, will usually reverse their diabetes after surgery.

    Just remember that diabetes is not a death sentence, there are several medicines that control blood sugar quite effectively and, in effect, these medicines "reverse" diabetes, also. And remember also that, for persons with type 2 diabetes, controlling blood pressure and taking statin drugs to prevent heart attacks and strokes, are actually far more important in preventing premature death and disability than super-strictly controlling blood sugar. This has been proved in all the major clinical trials of diabetes treatment.

    Type 2 diabetes also can be prevented or delayed with diet and exercise or with glucose-lowering medicines (metformin is the most tested one). However, this is not the same as saying that getting overweight and avoiding exercise are the only causes of type 2 diabetes. Both overweight and diabetes have genetic and epi-genetic causes that predispose some of us to become overweight and to be more likely to experience increased blood sugar if we do become overweight. 70% of Americans are overweight, but diabetes prevalence is actually higher in China, the Middle East, Mexico, and many other places, probably largely due to epigenetic changes arising from a family history of malnutrition and famine, possibly several generations back. If you parents were slaves, or Native Americans, or economically poor, or from a country where famines occurred, this may predispose you to weight gain and high blood sugar (as well as high blood pressure and other problems). This makes it doubly important for you to control what you eat and get lots of exercise. Life is not fair, at least as far as diabetes is concerned! Don't be ashamed of diabetes and don't let others blame you if you have it!

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  • The Type 2 Diabetes Handbook: Six Rules for Staying Healthy with Type 2 Diabetes

    The Type 2 Diabetes Handbook: Six Rules for Staying Healthy with Type 2 Diabetes Summary

    Based on the most recent research on Type 2 diabetes, this invaluable and practical health reference focuses on balancing diet, medication, and exercise to achieve optimal health. A host of potential complications of diabetes are discussed in detail, including eye-, kidney-, heart-, nerve-, and foot-related problems. Emotional aspects of being diabetic are also discussed. Filled with illustrations, charts, tables, and worksheets, this is a proven, user-friendly guide for living with and managing diabetes.

    Details Published

    Addicus Books Independent Publishers Group an imprint of #<Fortitude::Tags::TagReturnValue:0x007f2d3e6a0f28> on Jun 01, 2012

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    Type 2 Diabetes: Methods and Protocols - Free eBooks Download

    Type 2 Diabetes: Methods and Protocols

    Author. Date: 10 Dec 2015, Views:

    2009-07-10 | ISBN: 1934115150, 1617794929 | PDF | 278 Pages | 5.78 MB

    Diabetes is now reaching epidemic proportions, and the associated complications of this disease can be disabling and even life-threatening. In Type 2 Diabetes: Methods and Protocols, leading investigators provide up-to-date explanations of commonly used laboratory protocols used in diabetes research. Covering the commonly described in vivo and in vitro model systems, the volume ultimately leads to an overall view of how cellular dysfunction and degeneration leads to susceptibility and diabetes disease progression. Written in the highly successful Methods in Molecular Biology series format, chapters include brief introductions to their respective subjects, lists of the necessary materials and reagents, step-by-step, readily reproducible protocols, and expert notes on troubleshooting and avoiding known pitfalls. Comprehensive and cutting-edge, Type 2 Diabetes: Methods and Protocols offers succinct, proven techniques to aid research scientists and clinicians in continuing the study of this debilitating disease.

    Copyright Disclaimer:
    This site does not store any files on its server. We only index and link to content provided by other sites. Please contact the content providers to delete copyright contents if any and email us, we'll remove relevant links or contents immediately.



    Handbook of Diabetes, 4th Edition, Excerpt #6: Epidemiology and Aetiology of Type 2 Diabetes

    Handbook of Diabetes, 4th Edition, Excerpt #6: Epidemiology and Aetiology of Type 2 Diabetes

    Epidemiological studies of diabetes prevalence are often based upon age and self-reported diagnosis. Consequently differentiating type 1 and type 2 patients in population studies is difficult. The most recent authoritative review of global prevalence published by the International Diabetes Federation (IDF) acknowledges these drawbacks. However, as 85 – 95% globally of all adult diabetes is type 2 then total

    prevalence rates will overwhelmingly relate to it.

    The IDF has also published adult prevalence rates for impaired glucose tolerance (IGT) which closely reflect those for type 2 diabetes. Conversion rates from IGT to diabetes have been reported at 5 – 11% per annum….

    Overall prevalence corrected for age for both type 2 diabetes and IGT is set to increase from 6.0% to 7.3% and 7.5% to 8.0% respectively over the 18 years from 2007 to 2025 – an absolute increase from 246 to 380 and 308 to 418 million persons aged 20 – 79 years, respectively (Figure 7.1).

    The highest rates are currently in the Eastern Mediterranean and Middle East with North and South America close behind. These reflect the increased life expectancy and overall ageing of the North American population (diabetes is more common in older years). In terms of absolute numbers, the Western Pacific region (particularly China) will have the largest increase of nearly 50%, to 100 million people with diabetes by 2025.

    The highest number of people with diabetes is currently in the 40 – 59-year-old age group, but there will be almost parity with 60 – 79 year olds by 2025, at 166 and 164 million worldwide respectively.

    There is considerable variation within each region, however. For example, in the Western Pacific, the tiny island of Nauru has a comparative prevalence in 2007 of 30.7%, whilst nearby Tonga has less than half that rate at 12.9%, the Philippines 7.6% and China 4.1%.

    In the European region, comparative rates range from 1.6% in Iceland to 7.9% in Germany, Austria and Switzerland. The UK rate is 2.9% age adjusted and 4.0% absolute, increasing to 3.5% and 4.6% respectively in 2025 (representing an increase from 1.7 to 2.16 million in absolute numbers).

    Urban versus rural

    There is a global trend for rates of diabetes to increase in populations as they move from a rural to an urban existence. The reasons are unclear but probably relate to both decreasing physical activity as well as dietary changes. For example, rural Chinese have a prevalence of type 2 diabetes of 5%, less than half the rate of Singaporean Chinese (10.5%). Much larger differences are seen in South Asian, Hispanic, African and Polynesian peoples (Figure 7.2).

    Impaired glucose tolerance

    Comparative prevalence for IGT vary by region with rates almost double those for type 2 diabetes in Africa, but slightly lower elsewhere. These differences are almost certainly a reflection of socio-economic factors as well as a paucity of studies in many African countries where extrapolation is necessary between very different populations. In Europe, the comparative prevalence will increase slightly from 9.1% in 2007 to 9.6% in 2025, representing an absolute change from 65.3 to 71.2 million (UK figures 4.7% to 4.9%, 2.17 to 2.4 million respectively).

    Reported incidence rates vary according to population under study and year of observation. For white Europid populations, rates of 0.1 – 1% per annum have been reported. For Hispanic populations in the USA, rates of 2.8% were recorded in the San Antonio Study, similar to those of the Pima Indians in Arizona (approximately 2.5%), and Australian aborigines (2.03%).

    Over 20 years, incidence in the Pima has not changed although the age of onset has been declining. The occurrence of type 2 diabetes in adolescence is now a great cause for concern worldwide. In US Asian and Pacific Islanders, for example, rates of 12.1/100,000 patient – years have been reported in 10 – 19 year olds, similar to rates reported for type 1 diabetes. In the UK, the overall incidence for < 16 year olds is much lower, at 0.53 per/100,000 patient-years, but 10 times more common in South Asian or black African compared to white children.

    The rural:urban ratio remains for incidence even in the presence of other risk factors such as central obesity. In Japanese, there is an approximately threefold increase in incidence for obese urban compared to rural populations (15.8 versus 5.8% over 10 years). Similarly, there is a twofold increase in incidence for USA versus Mexican Hispanic people corrected for age and economic circumstance, probably a reflection of changes in diet and lifestyle. For the Pima, the contrast is more striking, with a > 5 – fold increase in those living in the US compared to northern Mexico.

    The magnitude of these figures has opened a debate on population screening for diabetes, but a Health Technology Assessment report in the UK from 2007 and a report from the US Preventive Services Task Force in 2008 both concluded that there is not enough evidence at present to support such a policy.

    Risk factors for development of type 2 diabetes

    About 80% of people with type 2 diabetes are obese, and the risk of developing diabetes increases progressively as the BMI (weight (kg)/height (m) 2) increases. A BMI > 35 kg/m 2 increases the risk of type 2 diabetes developing over a 10-year period by 80-fold, as compared to those with a BMI < 22 kg/m 2 Latest data from the NHANES survey in the USA confirm a 6 – 10-fold increased lifetime risk of type 2 diabetes for 18 year olds with a BMI > 35 kg/m 2 compared to those < 18.5 kg/m 2 with an associated average 6 – 7 year reduction in overall life expectancy. Obesity is still widely defined as a BMI > 30 kg/m 2 although BMI is not an accurate reflection of fat mass or its distribution, particularly in Asian people. A simple waist circumference may be better (see metabolic syndrome below).

    The pattern of obesity is also important in that central fat deposition has a much higher risk for development of diabetes compared to gluteofemoral deposition. In clinical practice such central obesity can be assessed by measuring the weight:hip circumference ratio, but it is unclear whether this has any advantage over a simple waist circumference. Fat deposition at other sites, particularly muscle, liver and islets, may contribute to metabolic defects and insulin resistance (so-called lipotoxicity).

    Physical exercise and diet

    Low levels of physical exercise also predict the development of type 2 diabetes, possibly because exercise increases insulin sensitivity and helps prevent obesity (Figure 7.4). Subjects who exercise the most have a 25 – 60% lower risk of developing type 2 diabetes regardless of other risk factors such as obesity and family history.

    There has been extensive research into the role of diet as a risk factor for type 2 diabetes. A study in over 10,000 35 – 55 year olds found that a diet containing large quantities of soft drinks, burgers, sausages and low fiber explained 5.7% of insulin resistance as assessed by the HOMA model. There were 77,440 person-years in the study with 427 incident cases of type 2 diabetes.

    The Diabetes Prevention Program and Diabetes Prevention Study in the USA and Finland have shown that lifestyle modifications with moderate exercise and modest weight loss can dramatically reduce the number progressing from IGT to type 2 diabetes and reinforce the importance of lifestyle factors in the cause of diabetes.

    Insulin resistance can be estimated from the amount of glucose that is infused intravenously in order to maintain a constant blood glucose during a simultaneous intravenous insulin infusion. This method is cumbersome, however, and for population purposes it has been largely superseded by the HOMA (homeostasis model assessment) estimate of steady-state β cell function (HOMA B) and insulin sensitivity (HOMA S) as percentages of normal. These can be derived from a single fasting plasma C peptide, insulin and glucose concentration. Insulin resistance (or, more correctly, diminished insulin sensitivity) precedes the onset of diabetes and can worsen with increasing duration.

    Hormones and cytokines

    Visceral fat liberates large amounts of non-esterified fatty acids (NEFAs) through lipolysis, which increases gluoconeogenesis in the liver and impairs glucose uptake and utilization in muscle. NEFAs may also inhibit insulin secretion, possibly by enhancing the accumulation of triglyceride within the β cells. In addition, adipose tissue produces cytokines, such as TNF-α. resistin and IL-6, all of which have been shown experimentally to interfere with insulin action. TNF-α has been shown to inhibit tyrosine kinase activity at the insulin receptor and decrease expression of the glucose transporter GLUT-4.

    Adiponectin is a hormone with antiinflammatory and insulin-sensitizing properties that is secreted solely by fat cells. It suppresses hepatic gluconeogenesis and stimulates fatty acid oxidation in the liver and skeletal muscles, as well as increasing muscle glucose uptake and insulin release from the β cells. Circulating adiponectin is reduced in obesity and a recent meta-analysis showed that the relative risk for diabetes was 0.72 for every 1-log μ g/mL increment in adiponectin level.

    Resistin is an adipocyte-secreted hormone that increases insulin resistance and was first described in rodents, being found in increased levels in experimental obesity and diabetes. In humans, it appears to be derived largely from macrophages, however, and its precise role in human diabetes is uncertain, although higher circulating levels have been found in some people with type 2 diabetes.

    Leptin is an adipokine that was found to be absent in the ob/ob mouse model of obesity and diabetes. Its normal function is to suppress appetite, thus providing a candidate mechanism linking weight gain and appetite control. Although abnormal leptin function has been described in humans, these defects are very rare and paradoxically high levels have been found in type 2 diabetes. Ghrelin is a recently described peptide secreted from the stomach and may act as a hunger signal. Circulating levels are negatively correlated with BMI and are suppressed by food intake. It has no known role in human diabetes but antagonism may provide a therapeutic target. Finally there is often increased sympathetic nervous system activity in obesity, which might also increase lipolysis, reduce muscle blood flow and thus glucose delivery and uptake, and therefore directly affect insulin action.

    Many of these cytokines are involved in the acute-phase response and it is therefore not surprising that circulating markers such as C-reactive protein and sialici acid are increased in type 2 diabetic patients, as well as in those who later go on to develop the condition. Because these markers have also been found to be elevated in patients with atherosclerosis, a unifying hypothesis has evolved proposing that inflammation may be a common precursor and link between diabetes and coronary artery disease.

    Evidence for a genetic basis for type 2 diabetes comes from a clear familial aggregation, but it does not segregate in a classic Mendelian fashion. About 10% of patients with type 2 diabetes have a similarly affected sibling. The concordance rate for identical twins is variously estimated to be 33 – 90% (17 – 37% in non-identical twins), but the interpretation of this is controversial as part of the explanation for the high concordance may be environmental rather than genetic.

    Unlike type 1, type 2 diabetes is not associated with genes in the HLA region. So far, 19 gene variants have been described and validated as being associated with type 2 diabetes. Of these, the strongest is TCF7L2; 15% of European adults carry two copies of the abnormal gene and they have double the lifetime risk of developing type 2 diabetes compared to the 40% who carry no copies. Carriers of the T risk allele have impaired insulin secretion and enhanced hepatic glucose output. Nearly all of the other described genes affect either β cell mass or function; few appear to have potential effects on insulin resistance.

    Thrifty phenotype hypothesis

    A link between low birthweight and later development of type 2 diabetes in a UK population has led to a hypothesis linking foetal malnutrition to impaired β cell development and insulin resistance in adulthood. Abundant adult nutrition and consequent obesity would then expose these problems, leading to IGT and eventually type 2 diabetes. This has been called the thrifty phenotype hypothesis (Figure 7.7).

    A meta-analysis of 31 populations involving 152,084 individuals from varying ethnic groups and 6,090 cases of diabetes was published in 2008. This confirmed a negative association between birthweight and diabetes in 23, but found a positive association in eight studies. The combined odds ratio for type 2 diabetes was 0.8 (95% CI 0.72 – 0.89) for each 1 kg increase in birthweight. This relationship was strengthened if macrosomic (birthweight > 4 kg) and offspring of mothers with known type 2 diabetes were excluded (odds ratio (OR) 0.67, 95% CI 0.61 – 0.73). Notably there was a tendency for a positive relationship in North American populations largely due to higher rates of maternal obesity and gestational diabetes. Adjustment for socio-economic status had no effect, but adjustment for achieved adult BMI attenuated the relationship.

    With increasing maternal obesity and gestational diabetes mellitus (GDM), it is conceivable that the relationship will change to the pattern currently seen in Native Americans which is more U shaped. However, it is still unclear whether low birthweight is a causative factor or a sign of other potential mechanisms which may predispose to later diabetes.

    This is a proposal that type 1 and type 2 diabetes are essentially the same in that both result ultimately from β cell failure. The aetiology obviously differs but superimposed insulin resistance drives the process. Three accelerators are proposed: constitution – individuals have increased β cell apoptosis; insulin resistance – underpinned by physical inactivity and visceral adiposity; and autoimmunity – mainly operative in younger patients and linked to HLA susceptibility alleles. The overlapping driver of obesity would explain increasing rates of ‘type 1′ and ‘type 2′ diabetes. This intriguing idea is currently widely debated and awaits confirmatory studies.

    The aggregation of obesity, hyperglycemia, hypertension and hyperlipidemia in people with both type 2 diabetes and cardiovascular disease is now termed the metabolic syndrome (Table 7.1). This concept is not new, it is said to have been first described in 1923, but latterly there have been attempts to standardize its definition.

    Since these definitions appeared, there has been considerable debate as to their relative strengths and weaknesses. Indeed, there is some debate as to whether this constitutes a true syndrome at all and whether they add anything to predictive models for type 2 diabetes and coronary artery disease. A major problem is the correlation of many of the features. In prospective studies, fasting plasma glucose (FPG) is overwhelmingly linked to subsequent development of diabetes, but much less so with coronary artery disease. Thus the predictive utility of the metabolic syndrome as a concept adds little to its constituent risk factors when they are used individually. The long – term usefulness of the definition of the metabolic syndrome for identification and intervention in order to prevent diabetes and cardiovascular disease has yet to be demonstrated.

    β cell dysfunction

    Type 2 diabetes develops because of a progressive deterioration of β cell function, coupled with increasing insulin resistance for which the β cell cannot compensate. At the time of diagnosis β cell function is already reduced by about 50% and continues to decline regardless of therapy (Figure 7.8).

    The main defects in β cell function in type 2 diabetes are a markedly reduced first- and second-phase insulin response to intravenous glucose, and a delayed or blunted response mixed meals (Figure 7.9). There are also alterations in pulsatile and daytime oscillations of insulin release. Some researchers have found increases in the proportions of plasma proinsulin and split proinsulin peptides relative to insulin alone. Many of these abnormalities can be found in people with IGT and even in normoglycemic first-degree relatives of people with type 2 diabetes, indicating that impaired β cell function is an early and possibly genetic defect in the natural history of type 2 diabetes (Figure 7.10).

    The most common histological abnormality found in the islets of patients with type 2 diabetes is the presence of insoluble amyloid fibrils lying outside the cells. These are derived from islet amyloid polypeptide (IAPP, also sometimes known as amylin). This is co-secreted with insulin in a molar ratio of 1:10 – 50. Although IAPP is reported to impair insulin secretion and to be toxic to the β cell, its precise role in the pathogenesis of type 2 diabetes is uncertain because deposits can be found in up to 20% of elderly people who had completely normal glucose tolerance in life.

    β Cell mass is thought to be decreased by only 20 – 40% in type 2 diabetes and this clearly cannot explain the > 80% reduction in insulin release that is observed. There must therefore be additional functional defects in the β cell, perhaps mediated by glucose or lipid toxicity. It is likely that IAPP contributes to this process.

    Both insulin resistance and β cell dysfunction are early features of glucose intolerance, and there has been much debate as to whether one is the primary defect and precedes the other. In practice, the contribution of insulin resistance and β cell dysfunction varies considerably between patients, as well as during the course of the disease. Usually, there is a decline in both insulin sensitivity and insulin secretion in patients who progress from IGT to diabetes and undoubtedly environmental and genetic factors contribute to this process (Figure 7.11).

    Next Week: Other types of diabetes

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    Handbook of Diabetes, 4th edition - Bilous - Wiley Online Library

    Handbook of Diabetes, 4th edition About this Book

    Over three editions the Handbook of Diabetes has built a reputation as an essential practical manual on the assessment and management of patients with diabetes. Previously written by Gareth Williams and John Pickup, the book has been completely revised by Rudy Bilous and Richard Donnelly to reflect recent changes in diabetes treatment and care. It contains information on the new IFCC units for measuring blood glucose and the latest drugs being used to combat diabetes, as well as alternative methods of insulin delivery.

    The book has been fully updated and redesigned to make it even more user-friendly, and contains case histories, practice points, and landmark clinical trials highlighted in color in each chapter where appropriate. It also features an entirely new set of clinical photographs, and all 250 images from the book can be downloaded from the companion CD for use in presentations.

    The Handbook of Diabetes is the ideal practical handbook for all health professionals with an interest in diabetes care.

    Table of contents

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