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The Ambulatory Reversal ProgramAmbulatory. www.themegallery.com Overview In today’s society, where inactive lifestyles and obesity are becoming increasingly.

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Presentation on theme: "The Ambulatory Reversal ProgramAmbulatory. www.themegallery.com Overview In today’s society, where inactive lifestyles and obesity are becoming increasingly."— Presentation transcript:

1 The Ambulatory Reversal ProgramAmbulatory

2 Overview In today’s society, where inactive lifestyles and obesity are becoming increasingly common, the incidence of diabetes is growing rapidly. Recent economic data shows soaring numbers of money spent and lost to fight diabetes both in the United States and Worldwide. Diabetes Wellness Clinics of America

3 Pedro J Martinez, M.D., C.M.C.M.  Board Certified Internal Medicine  Board Certified in Managed Care Medicine  Board eligible Geriatrics  Health Ministries Director, Arizona Conference  Office Director, Apologetics, Arizona Conference  Commissioned Minister, Arizona Conference  Medical Evangelist, Arizona Conference  Guatemala  Mexico  Chairman – Health Advisory Committee, NAD  Hope Medical Institute, Medical Director  Hope Diabetes Center Medical Director  PM Ministries [Internet Ministries], Director  License Minister  Doctor in Practical Ministries –Candidate  Master of Art in Biblical Counseling - Candidate Diabetes Wellness Clinics of America

4 Diabetes Mellitus

5  Diabetes is a serious disease with far-reaching consequences.  In 2007, the disease and its complications cost the United States about $174 billion. Direct costs had doubled since 2000 and costs are expected to continue to increase.  Type 1 and type 2 diabetes currently affect over 24 million Americans, or 8% of the population.  Additionally, an estimated 5.2 million people remain undiagnosed, and more than 60 million Americans have pre-diabetes, a precursor condition characterized by plasma glucose levels that are above normal but below the values diagnostic of diabetes Diabetes Wellness Clinics of America

6 Diabetes – an Unfolding Epidemic world wide will reach 300 million by 2025 World Health Organisation, September 1998 WHO estimates that the number of diabetics Increase in the number of people with diabetes from 150 million to 220 million – 10 years from now – yearly growth of 3.9%. Source: Amos A.., McCarty DJ, Zimmet P: Diabet. Med. 1997; The cost of treating people with diabetes is expected to amount to about USD 1 trillion annually – in the US in 2025 Dr G Bernstein, former president of ADA

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8 The evolution of mankind 2.5 mn years50 years Diabetes Wellness Clinics of America

9  Prevalence of obesity increased by 61% since 1991  More than 50% of US adults are overweight  Body mass index (BMI) and weight gain are major risk factors for diabetes:  BMI is overweight  BMI >30 is obese The Prevalence of Diabetes and Obesity Mokdad AH, et al. Diabetes Care. 2000;23: Mokdad AH, et al. JAMA. 1999;282: Mokdad AH, et al. JAMA. 2001;286: Prevalence (%) Diabetes Mean Body Weight kg Year Diabetes Wellness Clinics of America

10 Normal Type 2 Diabetes Courtesy of Wilfred Y. Fujimoto, MD. Visceral Fat Distribution: Normal vs Type 2 Diabetes

11 Total Prevalence of Diabetes in Americans Aged =20 Years by Age Group (2005)

12 Current Treatment Goals for Glycemic Control HDC < 6.0% < 100 mg/dL <140 mg/dL

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14  Metabolic Complications Ketoacidosis Hyperosmolar nonketotic syndrome Hypoglycemia  Macrovascular Complications Cardiovascular disease Cerebrovascular disease Peripheral vascular disease  Microvascular Complications Diabetic neuropathy Diabetic retinopathy Diabetic nephropathy Diabetic Metabolic, Macrovascular, and Microvascular Complications Abbott KC, et al. BMC Endocr Disord. 2003;3:1. Reusch JEB. J Clin Invest. 2003;112: Sheetz MJ, King GL. JAMA. 2002;288: Williams R, et al. Diabetologia. 2002;45:S13-S17. Diabetes Wellness Clinics of America

15 The Defect Insulin Resistance Insulin Resistance Liver Dysfunction PancreasDysfunction Small Bowel Hormonal Imbalance Diabetes Wellness Clinics of America

16 Unmet Therapeutic Needs in Type 2 Diabetes

17 b-Cell Function Declines Regardless of Intervention in Type 2 Diabetes Ambulatory Reversal Program

18 The Ambulatory Reversal Program Hope Medical Institute ARP

19 Overview The Ambulatory Reversal Program [ARP] is the most cost effective non-residential [out-patient], functional lifestyle and health maintenance program of its kind. The Ambulatory Reversal Program [ARP] is the most cost effective non-residential [out-patient], functional lifestyle and health maintenance program of its kind. Based on the Genesis Agenda with the ARP protocols Based on the Genesis Agenda with the ARP protocols It is a broad base, scientifically sounded, evidence based, affordable comprehensive and easy to follow lifestyle program It is a broad base, scientifically sounded, evidence based, affordable comprehensive and easy to follow lifestyle program Facilitate the transition from a live-in [Residential] to the “real life” Facilitate the transition from a live-in [Residential] to the “real life” Culturally sensitive Culturally sensitive Enhances the replication, preservation, and regeneration [neogenesis] of the beta cell Enhances the replication, preservation, and regeneration [neogenesis] of the beta cell Diabetes Wellness Clinics of America

20 Overview Naturally control the appetite, facilitating a significant amount of weight loss Naturally control the appetite, facilitating a significant amount of weight loss Reduce or eliminate the insulin resistance Reduce or eliminate the insulin resistance Is fast, fun, motivating with a high degree of compliance Is fast, fun, motivating with a high degree of compliance Our programs emphasize a non-new age progressive functional lifestyle, exercise and stress reduction program. Our programs emphasize a non-new age progressive functional lifestyle, exercise and stress reduction program. Although it is not a requirement to be a vegetarian. Although it is not a requirement to be a vegetarian. Our goal is to guide our patient in that direction by a gradual, cultural based well balanced process. Our goal is to guide our patient in that direction by a gradual, cultural based well balanced process. Diabetes Wellness Clinics of America

21 Overview  Offers Freedom of Choice Relaxing atmosphere Quick Satisfaction Warranty Fullness Diabetes Wellness Clinics of America

22 Stabilize Preserve Damage Control [Restore] Reversibility Phases of ARP Diabetes Wellness Clinics of America

23 1. Stabilize: the first immediate goal is to stabilize the patient [safety is always our main concern] in order to prevent those conditions that can and will put the patient life in jeopardy. Results can be seen within days, not weeks, months or years 1. Stabilize: the first immediate goal is to stabilize the patient [safety is always our main concern] in order to prevent those conditions that can and will put the patient life in jeopardy. Results can be seen within days, not weeks, months or years 2. Preserve. Our intensive program is designed to preserve beta cells that remain in your pancreas by slowing and/or eliminating the destruction of it 2. Preserve. Our intensive program is designed to preserve beta cells that remain in your pancreas by slowing and/or eliminating the destruction of it

24 3. Restore: Beta cell regeneration is not Science Fiction. Since 1998 evidence has been accumulated pointing in that direction. 3. Restore: Beta cell regeneration is not Science Fiction. Since 1998 evidence has been accumulated pointing in that direction. – The patient will be empowered with all the tools necessary to actively participate in the healing process that will prevent and/or reverse diabetes 4. Rebuild: Quality of life is essential to us. 4. Rebuild: Quality of life is essential to us. – Physically: A well balance exercise program will be tailor to every patient needs. – Mentally: Patient will be able to enjoy the true understanding of the positive thinking [based on evidence not on theory]

25 The Deadly Quartet  Abdominal Obesity  Men: > 102 cm [>40 in]  Female: >88 cm [35 in]  Dyslipidemia  Triglycerides > 150  HDL <40 in men, < 50 in female  Fasting glucose >110  High blood pressure >130/85

26 Our Goal A normal glycated hemoglobin (HbA1c), the same as a person without diabetes

27 Mission To improve the quality of lives and to reduce or eliminate diabetes complications through a new community outreach, evidence and scientifically based program. ARP is based on an innovative and new treatment paradigm, education and research, leading to the prevention and/or reversal of Diabetes Mellitus

28 Our Philosophy “One of the mantras of diabetes care is that the patient should be in charge” Patient-Centered Care

29 Synchronized Secuence of Event Diabetes Wellness Clinics of America

30 The Issues Diagnosis 1.Type I 2.Type II Production Apoptosis Neo-genesis Stress Gluco- toxicity Lipo-toxicity Diabetes Utilization Insulin resistance Visceral Obesity Hormonal Balance Glucagon GLP-1 Adrenal system

31 1 Reduce ApoptosisApoptosis New Treatment Paradigm 2 Increase Beta Cell ReplicationBeta Cell 3 Increase GLP-1GLP-1 4 Reduce GlucagonGlucagon 5 Decrease Free Fatty AcidsFree Fatty Acids 6 Decrease Insulin ResistanceInsulin Resistance 7 Reduce HyperinsulinemiaHyperinsulinemia Woerle H, et al., Diabetes 2003;52”[Suppl 1]:A351

32 Synchronized Sequence Reversibility Regenerator Damage control Stabilization Psychological /Spirit Complementary Med DiaFiber Plus ARP Protocol

33 Clinical Flow 7 days Collect Information Stabilization Focus on Physiology Stabilization Initiate Level 1 Stabilization Monitor Progress Damage Control First visit 2 nd Visit3 rd Visit 4» Visit 14 days 21 days

34 Services and Programs Diabetes Wellness Clinics of America

35 Fundamental Defect Increased PP Overprod Glu High Elev SPM Insulin Resistance Acquired Obesity Unhealthy lifestyle Medication Glucose toxicities Lipo-toxicities Impaired Insulin Release Genetics Glucose toxicities Lipo-toxicities Glucagon Abnormalities Pre & Post Hyperglycemia Woerle H, et al., Diabetes 2003;52”[Suppl 1]:A351

36 Pancreatic Dysfunction Pancreas DIS DSG CBCM ACA IERI Impaired Early Release of Insulin Decreased Insulin Secretion Decreased Beta Cell Mass Decreased Sensitivity to Glucose Decreased secretion of Amylin

37 Beta Cell function 1 Apoptosis [program death of cell] Prevention Fiber Post-prandial walk 2 Beta Cell Replication Prevention Fiber GLP-1 3 Neogenesis Prevention Fiber GLP-1 Altern. Med. Butler AE, et al. Diabetes. 2003,52:

38 Postprandial Abnormalities in People with Type 2 Diabetes  Reduced early insulin release, increased glucagon secretion  Increased glucose release  From meal -- reduced hepatic sequestration  Endogenously produced Liver -- increased glycogenolysis and gluconeogenesis Kidney -- increased gluconeogenesis  Abnormal routes of glucose disposal  Decreased oxidation  Increased nonoxidative glycolysis  Increased hepatic glycogen cycling  Decreased muscle glucose uptake  Increased glucose uptake in other tissues (eg, kidney)

39 Real Issues Methods How are we doing this? Portion Calories Appetite Education Compliance Satisfaction

40 A Century of Diabetes Care DCCT UKPDS Pump therapy Human insulin Insulin analogs Type Insulin therapy Sulfonylureas Alpha-glucosidase Inhibitors Biguanide Glitazones Meglitinides Insulin therapy 1920 Type Diet

41 The Cost Diabetes Wellness Clinics of America

42 The Cost

43 Diabetes Mellitus Production [Homa B]Production [Homa B] Absolute deficiency of insulinAbsolute deficiency of insulin Relative deficiency of insulinRelative deficiency of insulin Utilization [Homa R]Utilization [Homa R] Insulin resistanceInsulin resistance

44 “Ticking Clock” Hypothesis WHO. Diabetologia 1985;28: ; Haffner SM et al. JAMA 1990;263: For Microvascular complications Macrovascular complications The “clock starts ticking” At onset of hyperglycemia Before the diagnosis of hyperglycemia

45 ARP -Physician 1st Structured –office based 1st Structured –office based Provider oriented Provider oriented provider to intervene on time provider to intervene on time Evidence based Evidence based Scientifically grounded Scientifically grounded Clinically tested Clinically tested Help Help Helps to target the root of the problems, no just the numbers Helps to target the root of the problems, no just the numbers Empower physician Empower physician Financially attractive Financially attractive Fast Fast –Glycemic control –Weight control

46 ARP -Patient Facilitate gradual lifestyle changes Facilitate gradual lifestyle changes Eliminate craving and food addiction Eliminate craving and food addiction Helps patient to feel free of counting calories Helps patient to feel free of counting calories Empower patient Empower patient Helps to eliminate in a safe and timely fashion, unnecessary drugs Helps to eliminate in a safe and timely fashion, unnecessary drugs Culturally sensitive Culturally sensitive High compliance High compliance Fast Fast Simple and affordable Simple and affordable Improve self-esteem Improve self-esteem Always full and satisfied Always full and satisfied Appetite control without drugs = weight loss Appetite control without drugs = weight loss

47 The Toxic Effect of Sugar Diabetes Wellness Clinics of America

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49 Metabolic Pathways Leading to Diabetic Microvascular Complications

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51 The Fiber Facto

52 Increase in fiber intake reduces the risk of having diabetes by 39% (P = 0.026) whereas the same increase in protein intake increases the risk by 38% Increase in fiber intake reduces the risk of having diabetes by 39% (P = 0.026) whereas the same increase in protein intake increases the risk by 38% Low dietary fiber and high protein intakes associated with newly diagnosed diabetes in a remote aboriginal community. Low dietary fiber and high protein intakes associated with newly diagnosed diabetes in a remote aboriginal community. The Importance of Fiber

53 The New England Journal of Medicine 5/11/00 A high intake of dietary fiber (50gms), particularly of the soluble type, above the level recommended by the ADA (35gm), in patients with type 2 diabetes. A high intake of dietary fiber (50gms), particularly of the soluble type, above the level recommended by the ADA (35gm), in patients with type 2 diabetes. –improves glycemic control –decreases hyperinsulinemia –lowers plasma lipid concentrations

54 Income

55 US Diabetics

56 Thank You!!!! Martin Pintos

57 Ambulatory care is any medical care delivered on an outpatient basis. Many medical conditions do not require hospital admission and can be managed without admission to a hospital. Ambulatory

58 Insulin resistance (IR) is the condition in which normal amounts of insulin are inadequate to produce a normal insulin response from fat, muscle and liver cells. insulin Insulin resistance in fat cells reduces the effects of insulin and results in elevated hydrolysis of stored triglycerides in the absence of measures which either increase insulin sensitivity or which provide additional insulin. Increased mobilization of stored lipids in these cells elevates free fatty acids in the blood plasma. Insulin resistance in muscle cells reduces glucose uptake (and so local storage of glucose as glycogen), whereas insulin resistance in liver cells results in impaired glycogen synthesis and a failure to suppress glucose production. High plasma levels of insulin and glucose due to insulin resistance are believed to be the origin of metabolic syndrome and type 2 diabetes, including its complications. Insulin resistance (IR) Insulin resistance is a condition in which the body produces insulin but does not use it properly.

59 Insulin resistance (IR) is the condition in which normal amounts of insulin are inadequate to produce a normal insulin response from fat, muscle and liver cells. insulin Insulin resistance in fat cells reduces the effects of insulin and results in elevated hydrolysis of stored triglycerides in the absence of measures which either increase insulin sensitivity or which provide additional insulin. Increased mobilization of stored lipids in these cells elevates free fatty acids in the blood plasma. Insulin resistance in muscle cells reduces glucose uptake (and so local storage of glucose as glycogen), whereas insulin resistance in liver cells results in impaired glycogen synthesis and a failure to suppress glucose production. High plasma levels of insulin and glucose due to insulin resistance are believed to be the origin of metabolic syndrome and type 2 diabetes, including its complications. Insulin resistance (IR) Part I

60 Insulin resistance is a condition in which the body produces insulin but does not use it properly. Insulin, a hormone made by the pancreas, helps the body use glucose for energy. Glucose is a form of sugar that is the body’s main source of energy. The body’s digestive system breaks food down into glucose, which then travels in the bloodstream to cells throughout the body. Glucose in the blood is called blood glucose, also known as blood sugar. As the blood glucose level rises after a meal, the pancreas releases insulin to help cells take in and use the glucose. When people are insulin resistant, their muscle, fat, and liver cells do not respond properly to insulin. As a result, their bodies need more insulin to help glucose enter cells. The pancreas tries to keep up with this increased demand for insulin by producing more. Eventually, the pancreas fails to keep up with the body’s need for insulin. Excess glucose builds up in the bloodstream, setting the stage for diabetes. Many people with insulin resistance have high levels of both glucose and insulin circulating in their blood at the same time. Insulin resistance increases the chance of developing type 2 diabetes and heart disease. Learning about insulin resistance is the first step toward making lifestyle changes that can help prevent diabetes and other health problems. Insulin resistance (IR) Part II

61 Impaired fasting blood sugar, impaired glucose tolerance, or type 2 diabetes. This occurs because the pancreas is unable to turn out enough insulin to overcome the insulin resistance. Blood sugar levels rise and diabetes is diagnosed. High blood pressure. The mechanism is unclear, but studies suggest that the worse the blood pressure, the worse the insulin resistance. Abnormal cholesterol levels. The typical cholesterol levels of a person with insulin resistance are low HDL, or good cholesterol, and high levels of another blood fat called triglycerides. Heart disease. The insulin resistance syndrome can result in atherosclerosis (hardening of the arteries) and an increased risk of blood clots. Obesity. A major factor in the development of insulin resistance syndrome is obesity -- especially abdominal obesity or belly fat. Obesity promotes insulin resistance and negatively impacts insulin responsiveness in a person. Weight loss can improve the body's ability to recognize and use insulin appropriately. Kidney damage. Protein in the urine is a sign that kidney damage has occurred, although not everyone uses this component to define insulin resistant syndrome. Insulin resistance (IR) What Are The Signs of Insulin Resistance Syndrome? Part III

62 Apoptosis. [1] is the process of programmed cell death (PCD) that may occur in multicellular organisms. Programmed cell death involves a series of biochemical events leading to a characteristic cell morphology and death, in more specific terms, a series of biochemical events that lead to a variety of morphological changes, including blebbing, changes to the cell membrane such as loss of membrane asymmetry and attachment, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation (1-4). Apoptosis

63 Glucagon-like peptide-1 (GLP-1) is derived from the transcription product of the proglucagon gene. Proglucagon is a precursor of glucagon, and several other components. It is generated in the alpha cells of the pancreas, and it consists of the following: Oxyntomodulin is a naturally occurring 37 amino acid peptide hormone found in the colon, produced by the oxyntic (fundic) cells of the oxyntic (fundic) mucosa. It has been found to suppress appetite. The major source of GLP-1 in the body is the intestinal L cell that secretes GLP-1 as a gut hormone. GLP-1 secretion by L cells is dependent on the presence of nutrients in the lumen of the small intestine. The secretagogues (agents that cause or stimulate secretion) of this hormone include major nutrients like carbohydrate, protein and lipid. Once in the circulation, GLP- 1 has a half life of less than 2 minutes, due to rapid degradation by the enzyme dipeptidyl peptidase-4. Glucagon-like peptide-1 (GLP-1)

64 Glucagon is an important hormone involved in carbohydrate metabolism. Produced by the pancreas, it is released when the glucose level in the blood is low (hypoglycemia), causing the liver to convert stored glycogen into glucose and release it into the bloodstream. The action of glucagon is thus opposite to that of insulin, which instructs the body's cells to take in glucose from the blood. However, glucagon also paradoxically stimulates the release of insulin, so that newly available glucose in the bloodstream can be up taken and used by insulin-dependent tissues. Glucagon

65 Fatty acids can be bound or attached to other molecules, such as in triglycerides or phospholipids. When they are not attached to other molecules, they are known as "free" fatty acids. The uncombined fatty acids or free fatty acids may come from the breakdown of a triglyceride into its components (fatty acids and glycerol). However as fats are insoluble in water they must be bound to appropriate regions in the plasma protein albumin for transport around the body. The levels of "free fatty acid" in the blood are limited by the number of albumin binding sites available. Free fatty acids are an important source of fuel for many tissues since they can yield relatively large quantities of ATP(Adenosine-5'-triphosphate ATP transports chemical energy within cells for metabolism). Many cell types can use either glucose or fatty acids for this purpose. In particular, heart and skeletal muscle prefer fatty acids. The brain cannot use fatty acids as a source of fuel; it relies on glucose, or on ketone bodies. Ketone bodies are produced in the liver by fatty acid metabolism during starvation, or during periods of low carbohydrate intake. Fatty acids

66 Hyperinsulinemia, present in people with diabetes mellitus type 2 or insulin resistance where excess levels of circulating insulin are in the blood. It is not diabetes, but it is often associated with metabolic syndrome and type 2 Diabetes. Hyperinsulinemia

67 The term Sagittal Abdominal Diameter (SAD) is a measure of Visceral Obesity [1]. In layman's terms, this is the size of one's belly. More specifically, SAD represents the distance from your back to your upper abdomen, midway between the top of the pelvis and the bottom of the ribs, measured while standing [2]. The term Sagittal Abdominal Diameter (SAD) is a measure of Visceral Obesity Sagittal Abdominal Diameter (SAD)

68 In mammals, the adrenal glands (also known as suprarenal glands) are the star-shaped endocrine glands that sit on top of the kidneys; their name indicates that position (ad-, "near" or "at" + renes, "kidneys"; and as concerns supra-, meaning "above"). They are chiefly responsible for regulating the stress response through the synthesis of corticosteroids and catecholamines, including cortisol and adrenaline, respectively. Adrenal glands

69 Insulin is a hormone with extensive effects on both metabolism and several other body systems (eg, vascular compliance). Insulin causes most of the body's cells to take up glucose from the blood (including liver, muscle, and fat tissue cells), storing it as glycogen in the liver and muscle, and stops use of fat as an energy source. When insulin is absent (or low), glucose is not taken up by most body cells and the body begins to use fat as an energy source (ie, transfer of lipids from adipose tissue to the liver for mobilization as an energy source). As its level is a central metabolic control mechanism, its status is also used as a control signal to other body systems (such as amino acid uptake by body cells). It has several other anabolic effects throughout the body. When control of insulin levels fails, diabetes mellitus results. Insulin is used medically to treat some forms of diabetes mellitus. Patients with Type 1 diabetes mellitus depend on external insulin (most commonly injected subcutaneously) for their survival because the hormone is no longer produced internally. Patients with Type 2 diabetes mellitus are insulin resistant, have relatively low insulin production, or both; some patients with Type 2 diabetes may eventually require insulin when other medications fail to control blood glucose levels adequately. Insulin is a peptide hormone composed of 51 amino acid residues. Insulin

70 Sulfonylurea (UK: Sulphonylurea) derivatives are a class of antidiabetic drugs that are used in the management of diabetes mellitus type 2 ("adult- onset"). They act by increasing insulin release from the beta cells in the pancreas. Sulfonylurea (Drug)

71 Metformin (INN; trade names Glucophage, Riomet, Fortamet, Glumetza, Obimet, Dianben, Diabex, Diaformin, and others) is an oral anti-diabetic drug from the biguanide class. It is the first-line drug for the treatment of type 2 diabetes, particularly in overweight and obese people and those with normal kidney function, [1][2][3] and evidence suggests it may be the best choice for people with heart failure. [4] Metformin is the most popular anti-diabetic drug in the United States and one of the most prescribed drugs in the country overall, with nearly 35 million prescriptions filled in 2006 for generic metformin alone. [5] It is also used in the treatment of polycystic ovary syndrome. Metformin (Drug)

72 Glibenclamide (INN), also known as glyburide (USAN), is an anti-diabetic drug in a class of medications known as sulfonylureas, It is sold in doses of 1.25 mg, 2.5 mg and 5 mg, under the trade names Diabeta, Glynase and Micronase in the United States and Daonil, Semi-Daonil and Euglucon in the United Kingdom. It is also sold in combination with metformin under the trade name Glucovance. Glibenclamide (Drug)

73 Chlorpropamide is an example of a drug class called sulphonylureas (derivatives are a class of antidiabetic drugs that are used in the management of diabetes mellitus type 2. They act by increasing insulin release from the beta cells in the pancreas). Chlorpropamide (Drug)

74 Edema formerly known as dropsy or hydropsy, is an abnormal accumulation of fluid beneath the skin, or in one or more cavities of the body. Generally, the amount of interstitial fluid is determined by the balance of fluid homeostasis, and increased secretion of fluid into the interstitium or impaired removal of this fluid may cause edema. Five factors can contribute to the formation of edema. It may be facilitated by increased hydrostatic pressure or reduced oncotic pressure within blood vessels, increased blood vessel wall permeability as in inflammation, obstruction of fluid clearance via the lymphatic or changes in the water retaining properties of the tissues themselves. Raised hydrostatic pressure often reflects retention of water and sodium by the kidney. [1 [1 Edema

75 Metabolism is the set of chemical reactions that occur in living organisms in order to maintain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories. Catabolism breaks down organic matter, for example to harvest energy in cellular respiration. Anabolism, on the other hand, uses energy to construct components of cells such as proteins and nucleic acids. The chemical reactions of metabolism are organized into metabolic pathways, in which one chemical is transformed into another by a sequence of enzymes. Enzymes are crucial to metabolism because they allow organisms to drive desirable but thermodynamically unfavorable reactions by coupling them to favorable ones, and because they act as catalysts to allow these reactions to proceed quickly and efficiently. Enzymes also allow the regulation of metabolic pathways in response to changes in the cell's environment or signals from other cells. Metabolism

76 Macrovascular disease is a disease of any large (macro) blood vessels in the body. This sometimes occurs when a person has had diabetes for a long time. Fat and blood clots build up in the large blood vessels and stick to the vessel walls. Three common macrovascular diseases are coronary disease (in the heart), cerebrovascular disease (in the brain), and peripheral vascular disease (in the limbs) Macrovascular

77 Microangiopathy (or microvascular disease) is an angiopathy affecting small blood vessels in the body. [1] It can be contrasted to macroangiopathy. Microangiopathy

78 Pathophysiology - This sometimes occurs when a person has had diabetes mellitus for a long time. High blood glucose levels cause the endothelial cells lining the blood vessels to take in more glucose than normal (these cells do not depend on insulin). They then form more glycoproteins on their surface than normal, and also cause the basement membrane to grow thicker and weaker. The walls of the vessels become abnormally thick but weak, and therefore they bleed, leak protein, and slow the flow of blood through the body. Then some cells, for example in the retina (diabetic retinopathy) or kidney (diabetic nephropathy), may not get enough blood and may be damaged. Nerves, if not sufficiently supplied with blood, are also damaged which may lead to loss of function (diabetic neuropathy). Pathophysiology

79 Hypoglycemia can produce a variety of symptoms and effects but the principal problems arise from an inadequate supply of glucose as fuel to the brain, resulting in impairment of function (neuroglycopenia). Derangements of function can range from vaguely "feeling bad" to coma, anymous seizures, and (rarely) permanent brain damage or death. The most common forms of moderate and severe hypoglycemia occur as a complication of treatment of diabetes mellitus treated with insulin or less frequently with certain oral medications. Hypoglycemia is usually treated by the ingestion or administration of dextrose, or foods quickly digestible to glucose. Endocrinologists (specialists in hormones, including those which regulate glucose metabolism) typically consider the following criteria (referred to as Whipple's triad) as proving that individual's symptoms can be attributed to hypoglycemia: 1.Symptoms known to be caused by hypoglycemia 2.Low glucose at the time the symptoms occur 3.Reversal or improvement of symptoms or problems when the glucose is restored to normal Hypoglycemia

80 Nonketotic hyperosmolar coma (nonketotic hyperglycaemia) is a type of diabetic coma associated with a high mortality seen in diabetes mellitus type 2. The preferred term used by the American Diabetes Association is hyperosmolar nonketotic state (HNS). Other commonly used names are hyperosmolar hyperglycemic nonketotic coma (HHNKC) [1] or hyperosmotic non-ketotic (HONK).It is also called Hyperglycaemic Hyperosmolar State(HHS),as some patients may have some ketonuria and it does not necessarily cause coma. [1] Nonketotic hyperosmolar coma

81 Ketoacidosis is a type of metabolic acidosis which is caused by high concentrations of ketone bodies, formed by the deamination of amino acids, and the breakdown of fatty acids. The two common ketones produced in humans are acetoacetic acid and β-hydroxybutyrate. This is most common in untreated type 1 diabetes mellitus, when the liver breaks down fat and proteins in response to a perceived need for respiratory substrate. It can also occur with people undergoing hunger strikes, lasting over 3 days, or people in a starvation state as the body is forced to break down fat for sustenance due to their lack of outside nutrition. Ketoacidosis can be smelled on a person's breath. This is due to acetone, a direct byproduct of the spontaneous decomposition of acetoacetic acid. It is often described as smelling like fruit or nail polish remover. [1] Ketoacidosis should not be confused with ketosis, which is one of the body's normal processes for the metabolism of body fat. In ketoacidosis, the body fails to adequately regulate ketone production causing such a severe accumulation of keto acids that the pH of the blood is substantially decreased. Ketoacidosis

82 Hb1c - Glycosylated (or glycated) hemoglobin (hemoglobin A1c, Hb 1c, or Hb A1c, A1C) is a form of hemoglobin used primarily to identify the average plasma glucose concentration over prolonged periods of time. It is formed in a non-enzymatic pathway by hemoglobin's normal exposure to high plasma levels of glucose. Glycosylation of hemoglobin has been implicated in nephropathy and retinopathy in diabetes mellitus. Monitoring the Hb A1c in type-1 diabetic patients may improve treatment. [ [ Measuring A1c Hb A1c - Glycosylated

83 Impaired Glucose Tolerance (IGT) is a pre-diabetic state of dysglycemia, that is associated with insulin resistance and increased risk of cardiovascular pathology. IGT may precede type 2 diabetes mellitus by many years. IGT is also a risk factor for mortality. [ [ Impaired Glucose Tolerance (IGT)

84 Hypertension, also referred to as high blood pressure, HTN or HPN, is a medical condition in which the blood pressure is chronically elevated. In current usage, the word "hypertension" [1] without a qualifier normally refers to systemic, arterial hypertension. [2 [2 Hypertension

85 Polycystic ovary syndrome (PCOS) is an endocrine disorder that affects approximately 5% of all women. [1] It occurs amongst all races and nationalities, is the most common hormonal disorder among women of reproductive age, and is a leading cause of infertility. [2][3] The principal features are weight problems, lack of regular ovulation and/or menstruation, and excessive amounts or effects of androgenic (masculinizing) hormones. The symptoms and severity of the syndrome vary greatly among women. While the causes are unknown, insulin resistance, diabetes, and obesity are all strongly correlated with PCOS. Polycystic ovary syndrome (PCOS)

86 Beta cells (beta-cells, β-cells) are a type of cell in the pancreas in areas called the islets of Langerhans. They make up 65-80% of the cells in the islets. Beta cells make and release insulin, a hormone that controls the level of Glucose in the blood. There is a baseline level of Glucose maintained by the liver, but it can respond quickly to spikes in blood glucose by releasing stored insulin while simultaneously producing more. The response time is fairly quick, taking approximately 10 minutes. Apart from insulin, beta cells release C-peptide, a byproduct of insulin production, into the bloodstream in equimolar quantities. C-peptide helps to prevent neuropathy, and other symptoms of diabetes related to vascular deterioration [1]. Measuring the levels of C-peptide can give a practitioner an idea of the viable beta cell mass. [2] β-cells also produce amylin, [3] also known as IAPP, islet amyloid polypeptide. Amylin functions as part of the endocrine pancreas and contributes to glycemic control. Amylin's metabolic function is now somewhat well characterized as an inhibitor of the appearance of nutrient [especially glucose] in the plasma. It thus functions as a synergistic partner to insulin. Whereas insulin regulates long term food intake, increased amylin decreases food intake in the short term.] Beta cells

87 Amylin, or Islet Amyloid Polypeptide (IAPP), is a 37-residue peptide hormone secreted by pancreatic β-cells at the same time as insulin (in a roughly 1:100 amylin:insulin ratio). [1] Islet, or insulinoma, amyloid polypeptide (IAPP, or amylin) is commonly found in pancreatic islets of patients suffering diabetes mellitus type 2, or harboring an insulinoma. While the association of amylin with the development of type 2 diabetes has been known for some time, [2] a direct causative role for amylin has been harder to establish. Recent results suggest that amylin, like the related beta-amyloid (Abeta) associated with Alzheimer's disease, can induce apoptotic cell-death in insulin- producing beta cells, an effect that may be relevant to the development of type 2 diabetes. [3] [3] Islet Amyloid Polypeptide (IAPP)

88 C-peptide is a peptide which is made when proinsulin is split into insulin and C-peptide. They split before proinsulin is released from endocytic vesicles within the pancreas -- one C- peptide for each insulin molecule. C-peptide is the abbreviation for "connecting peptide", although its name was probably also inspired by the fact that insulin is also composed of an "A" chain and a "B" chain. C-peptide was discovered in It should not be confused with c-reactive protein or Protein C. The first documented use of the C-peptide test was in C-peptide

89 Cardiovascular disease or cardiovascular diseases refers to the class of diseases that involve the heart or blood vessels (arteries and veins). [1] While the term technically refers to any disease that affects the cardiovascular system (as used in MeSH), it is usually used to refer to those related to atherosclerosis (arterial disease). These conditions have similar causes, mechanisms, and treatments. In practice, cardiovascular disease is treated by cardiologists, thoracic surgeons, vascular surgeons, neurologists, and interventional radiologists, depending on the organ system that is being treated. There is considerable overlap in the specialties, and it is common for certain procedures to be performed by different types of specialists in the same hospital. Cardiovascular disease

90 Cerebrovascular disease is a group of brain dysfunctions related to disease of blood vessels supplying the brain. Hypertension is the most important cause that damages the blood vessel lining endothelium exposing the underlying collagen where platelets aggregate to initiate a repairing process which is not always complete and perfect. Sustained hypertension permanently changes the architecture of the blood vessels making them narrow, stiff, deformed and uneven which are more vulnerable to fluctuations of blood pressure. A fall in blood pressure during sleep can lead to marked reduction in blood flow in the narrowed blood vessels causing ischemic stroke in the morning whereas a sudden rise in blood pressure can cause tearing of the blood vessels causing intracranial hemorrhage during excitation at daytime. Primarily people who are elderly, diabetic, smoker, or have ischemic heart disease, have cerebrovascular disease. All diseases related to artery dysfunction can be classified under a disease as known as Macrovascular disease. This is a simplistic study by which arteries are blocked by fatty deposits or by a blood clot. The results of cerebrovascular disease can include a stroke, or even sometimes a hemorrhagic stroke. Ischemia or other blood vessel dysfunctions can affect one during a cerebrovascular accident. Cerebrovascular disease

91 Peripheral vascular disease (PVD), also known as peripheral artery disease (PAD) or peripheral artery occlusive disease (PAOD), includes all diseases caused by the obstruction of large arteries in the arms and legs. PVD can result from atherosclerosis, inflammatory processes leading to stenosis, an embolism or thrombus formation. It causes either acute or chronic ischemia (lack of blood supply), typically of the legs. Peripheral vascular disease (PVD)

92 Diabetic neuropathies are neuropathic disorders that are associated with diabetes mellitus. These conditions are thought to result from diabetic microvascular injury involving small blood vessels that supply nerves (vasa nervorum). Relatively common conditions which may be associated with diabetic neuropathy include third nerve palsy; mononeuropathy; mononeuropathy multiplex; diabetic amyotrophy; a painful polyneuropathy; autonomic neuropathy; and thoracoabdominal neuropathy. Diabetic neuropathies

93 Diabetic retinopathy is retinopathy (damage to the retina) caused by complications of diabetes mellitus, which can eventually lead to blindness. It is an ocular manifestation of systemic disease which affects up to 80% of all patients who have had diabetes for 10 years or more [1]. Despite these intimidating statistics, research indicates that at least 90% of these new cases could be reduced if there was proper and vigilant treatment and monitoring of the eyes [citation needed]. Diabetic retinopathy

94 Diabetic nephropathy (nephropatia diabetica), also known as Kimmelstiel-Wilson syndrome and intercapillary glomerulonephritis, is a progressive kidney disease caused by angiopathy of capillaries in the kidney glomeruli. It is characterized by nephrotic syndrome and nodular glomerulosclerosis. It is due to longstanding diabetes mellitus, and is a prime cause for dialysis in many Western countries. Diabetic nephropathy


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