In the writings of Aretaios (Aretaeus) of Cappadocia, a Greek physicianswho lived during the period 120-200 A.D., there is a reference, probably to Diabetes. Amongst the disease described, he mentioned a condition associated with unquenchable thirst, excessive drinking of water and excessive passing of urine. The word "Diabetes" is perhaps derived from a Greek word signifying a siphon, appropriately describing how in the disease the fluid cannot be retained in the body. Greek physicians, like ancient Hindu physicians, used to taste the patient's urine to detect abnormal constituents. This unpleasant practice perhaps enabled them to detect diabetic patients. Thomas Willis, in 1764, observed that the urine of a diabetic patient was sweet and he surmised that it contained either sugar or honey. Diabetes mellitus comes from the Greek word "diabainein" meaning "to pass through," and the Latin word "mellitus" meaning "sweetened with honey." Put the two words together and you have "to pass through sweetened with honey."
The digestion of carbohydrate. The complex polysaccharide starch is broken down into glucose by the enzymes amylase and maltase (secreted by the small intestine).
Panel 2. Insulin secretion - Insulin secretion in beta cells is triggered by rising blood glucose levels. Starting with the uptake of glucose by the GLUT2 transporter, the glycolytic phosphorylation of glucose causes a rise in the ATP:ADP ratio. This rise inactivates the potassium channel that depolarizes the membrane, causing the calcium channel to open up allowing calcium ions to flow inward. The ensuing rise in levels of calcium leads to the exocytotic release of insulin from their storage granule. The process by which insulin is released from beta cells, in response to changes in blood glucose concentration, is a complex and interesting mechanism that illustrates the intricate nature of insulin regulation. Type 2 glucose transporters (GLUT2) mediate the entry of glucose into beta cells (see panel 2). As the raw fuel for glycolysis, the universal energy-producing pathway, glucose is phosphorylated by the rate-limiting enzyme glucokinase. This modified glucose becomes effectively trapped within the beta cells and is further metabolized to create ATP, the central energy molecule. The increased ATP:ADP ratio causes the ATP-gated potassium channels in the cellular membrane to close up, preventing potassium ions from being shunted across the cell membrane. The ensuing rise in positive charge inside the cell, due to the increased concentration of potassium ions, leads to depolarization of the cell. The net effect is the activation of voltage-gated calcium channels, which transport calcium ions into the cell. The brisk increase in intracellular calcium concentrations triggers export of the insulin-storing granules by a process known as exocytosis. The ultimate result is the export of insulin from beta cells and its diffusion into nearby blood vessels. Extensive vascular capacity of surrounding pancreatic islets ensures the prompt diffusion of insulin (and glucose) between beta cells and blood vessels. Insulin release is a biphasic process. The initial amount of insulin released upon glucose absorption is dependent on the amounts available in storage. Once depleted, a second phase of insulin release is initiated. This latter release is prolonged since insulin has to be synthesized, processed, and secreted for the duration of the increase of blood glucose. Furthermore, beta cells also have to regenerate the stores of insulin initially depleted in the fast response phase
How insulin works Panel 3. Insulin binding to the insulin receptor induces a signal transduction cascade which allows the glucose transporter (GLUT4) to transport glucose into the cell. [ magnify ] Insulin molecules circulate throughout the blood stream until they bind to their associated (insulin) receptors. The insulin receptors promote the uptake of glucose into various tissues that contain type 4 glucose transporters (GLUT4). Such tissues include skeletal muscles (which burn glucose for energy) and fat tissues (which convert glucose to triglycerides for storage). The initial binding of insulin to its receptor initiates a signal transduction cascade that communicates the message delivered by insulin: remove glucose from blood plasma (see panel 3). Among the wide array of cellular responses resulting from insulin ‘activation,’ the key step in glucose metabolism is the immediate activation and increased levels of GLUT4 glucose transporters. By the facilitative transport of glucose into the cells, the glucose transporters effectively remove glucose from the blood stream. Insulin binding results in changes in the activities and concentrations of intracellular enzymes such as GLUT4. These changes can last from minutes to hours. Panel 3. Insulin-mediated glucose uptake - Insulin binding to the insulin receptor induces a signal transduction cascade which allows the glucose transporter (GLUT4) to transport glucose into the cell. As important as insulin is to preventing too high of a blood glucose level, it is just as important that there not be too much insulin and hypoglycemia. As one step in monitoring insulin levels, the enzyme insulinase (found in the liver and kidneys) breaks down blood-circulating insulin resulting in a half-life of about six minutes for the hormone. This degradative process ensures that levels of circulating insulin are modulated and that blood glucose levels do not get dangerously low
What goes wrong in diabetes? The body’s response to blood sugar requires the coordination of an array of mechanisms. Failure of any one component involved in insulin regulation, secretion, uptake or breakdown can lead to the build-up of glucose in the blood. Likewise, any damage to the beta cells, which produce insulin, will lead to increased levels of blood glucose. Diabetes mellitus, commonly known as diabetes, is a metabolic disease that is characterized by abnormally high levels of glucose in the blood. Whereas non-diabetics produce insulin to reduce elevated blood glucose levels (i.e. after a meal), the blood glucose levels of diabetics remain high. This can be due to insulin not being produced at all, or not in quantities sufficient to be able to reduce the blood glucose level. The most common forms of diabetes are Type 1 diabetes (juvenile onset, 5-10% of cases), which is an autoimmune disease that destroys beta cells, and Type 2 diabetes (adult onset, 90-95% of cases), which is associated with insufficient insulin. In either case, diabetes complications are severe and the disease can be fatal if left untreated. Insulin is the foundation for the management of insulin-dependent diabetes. Unfortunately, the use of insulin is not a cure nor without side effects. In certain parts of the world, it is not even available. Insulin is also not completely effective in preventing complications of the disease such as blindness, heart disease, kidney failure, etc. While millions of men, women, and children await a life without diabetes, let us hope that policy makers and the scientific community can converge on strategies that promote discovery for a cure.
Insulin is a polypeptide hormone that travels around the bloodstream. Most of the cells in the body carry receptors for the molecule in their cell membranes. Once the hormone has become bound to one of these receptors, the receptor gives a signal to the cell's interior. This signal leads to many enzyme controlled reactions which, in turn lead to changes in the metabolism of the cell. Many of the effects of insulin depend on the particular cell type in which it stimulates. However, in nearly all of the cells that have insulin receptors in their cell membrane, the binding of insulin to the receptors leads to increased glucose uptake of the cell. The two types of cells that are the main exceptions are the brain and the liver. However, this is only due to the fact that these cells are readily permeable to glucose, even in the absence of insulin. Liver cell membranes do contain insulin and glucagon receptors, but binding of the hormone to them affects cellular processes other than glucose permeability. The animation below illustrates the way insulin brings about the increase in glucose uptake Glucose enters the cells of the body through glucose transporter (GLUT) proteins which are embedded within the cell membrane. This is a process called facilitated diffusion. When insulin binds to it's receptor, the intracellular domain of the receptor changes shape slightly . This sets off a chain of reactions. These reactions serve to activate certain enzymes. As a result, more glucose transporter proteins are released from intracellular stores and move to the plasma membrane and become embedded within it.
In general we can say that insulin favors anabolic reactions; glucagon, catabolic reactions. Put more simply, insulin favors storing energy and production of proteins while glucagon activates release of stored energy in the form of glucose or fatty acids. The actions of these two hormones on individual metabolic processes are summarized in the following table.
A protein-rich meal leads to release of both insulin and glucagon. The latter stimulates gluconeogenesis and release of the newly formed glucose from the liver to the blood stream. The very moderate rise in insulin associated with the protein meal stimulates uptake of the sugar formed in the liver by muscle and fat tissue.
One of the primary actions of insulin is to control movement of fatty acids in and out of adipocytes. It does this through two mechanisms; regulation of hormone-sensitive lipase and activation of glucose transport into the fat cell via recruitment of GLUT4. Storage of triglycerides after a meal is dependent upon insulin-stimulated glucose uptake and glycolysis. Fat cells take up both fatty acids and glucose simultaneously. The fatty acids come from the action of lipoprotein lipase at the capillary wall. Glucose uptake is stimulated by insulin and occurs through the insulin-sensitive glucose transport protein GLUT4. Thus insulin increases glucose uptake and glycolysis in fat cells, inhibits hormone-sensitive lipase and thereby increases storage of lipids as triglycerides in adipocytes.
The total lack of insulin leads to two metabolic crises; a marked increase in the rate of lipolysis in adipose tissue and activation of hepatic gluconeogenesis in spite of high plasma glucose levels. The dramatically increased rate of lipolysis in adipose tissue follows the lack of insulin inhibition of hormone-sensitive lipase. The increase in fatty acids that results leads to a massive synthesis of ketone bodies in the liver. These then exceed the buffer capacity of the blood, leading to ketoacidosis. Excess acid is a potent poison for the brain. Coma and death follow ketoacidosis. Blood glucose levels
Type 1 and type 2 diabetes have different causes. Yet two factors are important in both. First, you must inherit a predisposition to the disease. Second, something in your environment must trigger diabetes. Genes alone are not enough. One proof of this is identical twins. Identical twins have identical genes. Yet when one twin has type 1 diabetes, the other gets the disease at most only half the time. When one twin has type 2 diabetes, the other's risk is at most 3 in 4. In most cases of type 1 diabetes, people need to inherit risk factors from both parents. We think these factors must be more common in whites because whites have the highest rate of type 1 diabetes. Because most people who are at risk do not get diabetes, researchers want to find out what the environmental triggers are. One trigger might be related to cold weather. Type 1 diabetes develops more often in winter than summer and is more common in places with cold climates. Another trigger might be viruses. Perhaps a virus that has only mild effects on most people triggers type 1 diabetes in others. Early diet may also play a role. Type 1 diabetes is less common in people who were breastfed and in those who first ate solid foods at later ages. In many people, the development of type 1 diabetes seems to take many years. In experiments that followed relatives of people with type 1 diabetes, researchers found that most of those who later got diabetes had certain autoantibodies in their blood for years before. (Antibodies are proteins that destroy bacteria or viruses. Autoantibodies are antibodies 'gone bad,' which attack the body's own tissues.)
Blood sugar levels are dependent upon glucose uptake after meals and hepatic release of glucose between meals. The sugar released from the liver comes either from stored glycogen or production of glucose from lactate and amino acids. This production of glucose is largely responsible for stabilization of postprandial blood sugar levels. The hyperglycemia noted in type 2 diabetes partially results from lack of control over hepatic glucose formation due to resistance to insulin. It has recently become clear that part of this insulin effect occurs indirectly through insulin-sensitive receptors in the brain (more precisely, in the hypothalamus).
Type 2 diabetes has a stronger genetic basis than type 1, yet it also depends more on environmental factors. Sound confusing? What happens is that a family history of type 2 diabetes is one of the strongest risk factors for getting the disease but it only seems to matter in people living a Western lifestyle. Americans and Europeans eat too much fat and too little carbohydrate and fiber, and they get too little exercise. Type 2 diabetes is common in people with these habits. The ethnic groups in the United States with the highest risk are African Americans, Mexican Americans, and Pima Indians. In contrast, people who live in areas that have not become Westernized tend not to get type 2 diabetes, no matter how high their genetic risk. Obesity is a strong risk factor for type 2 diabetes. Obesity is most risky for young people and for people who have been obese for a long time.
Note that this figure applies both to uncontrolled diabetes type I and severe uncontrolled diabetes type II
Balance food intake with insulin (or oral agents) and activity to achieve blood glucose levels as near normal as possible. Achieve and maintain normal lipid (cholesterol) levels
Provide energy to reach and maintain short and long term body weight Reach and maintain normal growth and development in children and adolescents Prevent or treat complications Improve and maintain nutritional status Provide optimal nutrition for pregnancy
Consistency and timing of meals Timing of meals and administration of insulin Insulin plans should be designed to match the person’s eating pattern Monitor blood glucose regularly
Weight loss: 10-20# is sufficient Smaller meals and snacks Physical activity Monitor blood glucose and medications
Sucrose and sucrose foods may be substituted for other carbohydrates; not added to male plan
2. Diabetes MellitusDisease in which the body doesn’tproduce or properly use insulin,leading to hyperglycemia.
3. Carbohydrate Digestion
4. Insulin Secretion
5. What goes wrong in diabetes? Multitude of mechanisms Insulin Regulation Secretion Uptake or breakdown Beta cells damage
6. Action of Insulin on the CellMetabolism
7. Action of Insulin on Carbohydrate, Proteinand Fat Metabolism Carbohydrate Facilitates the transport of glucose into muscle and adipose cells Facilitates the conversion of glucose to glycogen for storage in the liver and muscle. Decreases the breakdown and release of glucose from glycogen by the liver
8. Action of Insulin on Carbohydrate, Proteinand Fat Metabolism Protein Stimulates protein synthesis Inhibits protein breakdown; diminishes gluconeogenesis
9. Action of Insulin on Carbohydrate, Proteinand Fat Metabolism Fat Stimulates lipogenesis- the transport of triglycerides to adipose tissue Inhibits lipolysis – prevents excessive production of ketones or ketoacidosis
10. Type I Diabetes Low or absent endogenous insulin Dependent on exogenous insulin for life Onset generally < 30 years 5-10% of cases of diabetes Onset sudden Symptoms: 3 P’s: polyuria, polydypsia, polyphagia
11. Type I Diabetes Cell
12. Type I Diabetes Genetic component to disease
13. Type II Diabetes Insulin levels may be normal, elevated or depressed Characterized by insulin resistance, diminished tissue sensitivity to insulin, and impaired beta cell function (delayed or inadequate insulin release) Often occurs >40 years
14. Type II Diabetes
15. Type II Diabetes Risk factors: family history, sedentary lifestyle, obesity and aging Controlled by weight loss, oral hypoglycemic agents and or insulin
16. Screening for DiabetesFasting Significance ActionBloodGlucose< 110 Normal Retest in 3 years>110 & IGT 1. Additional<126 testing 2. Check risk factors 3. MNT> 126 Diabetes 1. Confirm Likely by 2nd FBG 2. Treat DM
19. Medical Nutrition Therapy Maintain short and long term body weight Reach and maintain normal growth and development Prevent or treat complications Improve and maintain nutritional status Provide optimal nutrition for pregnancy
20. Nutritional Management for Type IDiabetesConsistency and timing of mealsTiming of insulinMonitor blood glucose regularly
21. Nutritional Management for Type IIDiabetes Weight loss Smaller meals and snacks Physical activity Monitor blood glucose and medications
22. Diabetes Control andComplications Trial 10 year randomized, controlled, clinical trial Determine the effects of glucose control on the development of long term microvascular and neurologic complications in persons with type I diabetes. 1441 participants, ages 13 to 39
23. Diabetes Control and Complications Trial Conventional therapy: 1 - 2 insulin injections, self monitoring B.G routine contact with MD and case manager 4X/year. Intensive therapy: 3 or more insulin injections, with adjustments in dose according to B.G monitoring, planned dietary intake and anticipated exercise.
24. Diabetes Control andComplications Trial Results: 76% reduction in retinopathy 60% reduction in neuropathy 54% reduction in albuminuria 39% reduction in microalbuminuria Implication: Improved blood glucose control also applies to person with type II diabetes.
25. Nutrition Recommendations Carbohydrate 60-70% calories from carbohydrates and monounsaturated fats Protein 10-20% total calories
26. Nutrition Recommendations Fat <10% calories from saturated fat 10% calories from PUFA <300 mg cholesterol Fiber 20-35 grams/day Alcohol Type I – limit to 2 drinks/day, with meals Type II – substitute for fat calories
32. 2003 Diabetic Exchange Lists Milk – 12 g. carbohydrate, 8 g. protein and 0-8 g. fat Meat and Meat Substitutes Very Lean Meat (7 g protein, 0-1 g. fat and 35 calories) Chicken, turkey – white meat Shellfish (clams, crab, lobster, shrimp)
33. 2003 Diabetic Exchange Lists Lean Meat (7 g protein, 3 g. fat and 55 calories) Select or choice beef, trimmed of fat Lean pork Poultry, turkey –dark meat
34. 2003 Diabetic Exchange Lists Medium Fat Meat (7 g protein, 5 g. fat and 75 calories) Most beef products – corned beef, ribs, prime grades Ground turkey Chicken – dark meat with skin High Fat Meat (7 g protein, 8 g. fat and 75 calories) All cheeses Processed meats, hot dogs
36. Carbohydrate Counting A serving of carbohydrate is considered 15 grams A serving of fruit or starch or 3 servings of vegetable is = to 1 carbohydrate One milk serving is considered equal to one carbohydrate
37. Carbohydrate Counting Example: Meal plan = 9 carbohydrate servings 4 fruit and 5 starches or 3 fruit + 4 starches + 3 vegetables and 1 milk or 2 fruit + 4 starches + 3 vegetables and 2 milk