Diabetes Mellitus part 1 narrated

Diabetes Mellitus : 

Diabetes Mellitus check it out

Diabetes Mellitus : 

Diabetes Mellitus Approx. 24 million Americans (8% of pop.) have diabetes mellitus (DM). 5.7 million (25%) are undiagnosed. 57 million Americans have pre-diabetes Prevalence of diabetes increases with age D/T insulin resistance and wt. gain. <20 y.o. = 0.22%; 20-65 y.o. = 10.7%; 65-74 y.o. = 23.1% The prevalence of diabetes is at least 2 to 4 times higher among non-Hispanic Black, Hispanic/Latino American, American Indian, and Asian/Pacific Islander women than among non-Hispanic white women. Total cost of DM in the U.S. was estimated at $174 billion in 2007. Medical cost for person with DM/yr in 2007 ~ $11,744, without DM ~ $5,106/yr.

Diabetes Mellitus : 

Diabetes Mellitus Diabetes is 5th leading cause of death in the U.S. & is co-morbidity factor for: Blindness (major cause of new cases in U.S.) Kidney failure (major cause in U.S.) Infections necessitating amputations of feet and legs D/T gangrene Birth defects, especially if mother’s blood glucose (BG) is poorly controlled Atherosclerosis: people with DM have 4x the risk vs. non-DM Hypertension (HTN): D/T increased stimulation of SNS & hyperinsulinemia

Diabetes Mellitus : 

Diabetes Mellitus DEFINITION: A heterogeneous syndrome characterized by disturbances in carbohydrate, fat and protein metabolism caused by hormone imbalances, chiefly insulin (produced by ß cells) and glucagons (produced by α cells). CHO abnormalities are manifest as hyperglycemia Lipid abnormalities are manifest as dyslipidemia (hypertriglyceridemia (HTG) and decreased high density lipoprotein (HDL) Protein abnormalities in Type 1 are manifest as muscle wasting

DM Diagnosis : 

DM Diagnosis NEW STANDARD AS OF JANUARY 2004 ESTABLISHED FOR WNL OF BG VALUES FBG: < 100 mg/dl WNL BG range: 70-99 mg/dl As of JULY 2009: recommendation to use Hemoglobin A1c as new diagnostic criteria: ≥6.5% = Diabetes ≥6.0 and <6.5 = high risk for diabetes development Major advantage: no need for fasting test

Classification of DM : 

Classification of DM Type 1 Type 2 Pre-diabetes – Impaired glucose tolerance Gestational Diabetes

Type 1 DM : 

Type 1 DM Type 1 (formerly referred to as IDDM or juvenile-onset) 1. Characteristics Accounts for 5-10% of people with DM Total or near total lack of insulin D/T destruction of beta cells Must inject insulin regularly to prevent diabetic ketoacidosis (DKA) and survive Insulin must be injected because it is a protein. GI tract enzymes would digest it if taken orally Hyperglucagonemia is present Usually develops suddenly, < 20 years. Peak incidence 10-14 years In older people DM may progress silently for several years. Are asymptomatic initially, symptoms appear gradually

Etiology of Type 1 DM : 

Etiology of Type 1 DM Auto-immunity: The body develops antibodies to its own islet beta cells & destroys them. 90% have histocompatibility locus antigens (HLA); autoantibodies present in 85-90% of individuals when fasting hyperglycemia is initially detected. Antibodies are present months or years before Sx indicating autoimmune attack. Idiopathic: 10% of Type 1 DM, unknown etiology Genetic predisposition is inherited through auto-immunity factors. Frequently no known relatives with DM in Type 1 Environmental factors (viruses - flu, mumps, measles, free radicals, toxins, infections, significant stress). Initiate DM by triggering an auto-immune reaction in those predisposed

Type 1 DM : 

Type 1 DM Honeymoon phase: A temporary remission of DM after initial treatment with insulin Etiology is unknown Likely relief from the constant hyperglycemia of uncontrolled diabetes, the insulin-producing cells of the pancreas become able to function normally Decreased need for exogenous insulin for up to one year

Type 2 Diabetes Mellitus : 

Type 2 Diabetes Mellitus (formerly referred to as NIDDM or adult-onset) Characteristics: Accounts for 90-95% of all diabetes Usually develops in people > 40 years old Genetics/family hx is the primary etiologic factor Onset is less dramatic, frequently Dx during routine PE or when person begins to develop chronic complications May or may not experience classic Sx of DM

Type 2 Diabetes Mellitus : 

Type 2 Diabetes Mellitus Characteristics: Usually associated with obesity (80% obese), remaining 20% who are non-obese are predominantly elderly) As body fat increases (central obesity), adipose and muscle tissues become more insulin resistant. Rarely develop ketosis since endogenous insulin is secreted Endogenous insulin may be low, normal, or elevated. Eventually ~ 60% will require insulin Many will require insulin during illness Controlled by diet, weight loss, oral drugs, insulin or other injectable agent, or combination

Impaired Glucose Tolerance : 

Impaired Glucose Tolerance Impaired Glucose Tolerance (IGT) is the name given to define blood glucose levels that are higher than normal, but below the level of a person with diabetes. IGT is a combination of: Impaired secretion of insulin  Reduced insulin sensitivity (insulin resistance)

Impaired Glucose Tolerance : 

Impaired Glucose Tolerance In people with IGT, the rise in blood glucose that occurs after consuming 75g glucose is greater than normal, although not as great as in people with type 2 diabetes.  Fasting blood glucose levels are normal or moderately raised. IGT carries a high risk of progressing to type 2 diabetes, leading to it being referred to as ‘pre-diabetes’ by, among others, the American Diabetes Association.

Impaired Glucose Tolerance : 

Impaired Glucose Tolerance The loss of early insulin secretion in IGT and type 2 diabetes is the result of malfunctioning of the pancreatic ß-cells.  In the long-term, high blood glucose levels are toxic to ß-cells, leading to further deterioration in ß-cell function and worsening blood glucose control. IGT is often associated with a cluster of inter-related cardiovascular risk factors known as the Metabolic Syndrome, Insulin Resistance Syndrome or Syndrome X. These are: High blood pressure (hypertension) High LDL-cholesterol (also called "bad" cholesterol) High triglycerides (TG) Low HDL-cholesterol (also called "good" cholesterol)

Prevention : 

Prevention Recently completed Diabetes Prevention Program studying obese people with IGT. Divided into 3 groups: Group 1 placed on very low fat diet and exercise (lost 15 lbs. on average); group 2 given metformin (Glucophage); and group 3 given placebo and general information about diet and exercise. Group 1 reduced risk by 58%, Group 2 by 31% Group 3 no risk reduction

Gestational Diabetes Mellitus (GDM) : 

Gestational Diabetes Mellitus (GDM) Occurs in 4% of pregnant women, usually during the 2nd or 3rd trimester D/T insulin antagonist hormones, glucagon, cortisol, growth hormone, epinephrine, and norepinephrine. These hormones block absorption of insulin causing insulin resistance. Additionally, in pregnancy the need for insulin can be up to three times greater than in non-pregnancy. In women with gestational diabetes, their bodies cannot make enough insulin to overcome insulin resistance.

Gestational Diabetes Mellitus : 

Gestational Diabetes Mellitus First diagnosed during pregnancy All high risk pregnant women should be screened between the 24th and 28th weeks of gestation. High risk includes: >25 years old Overweight Family history of diabetes High risk racial/ethnic group Hx of giving birth to infant weighing 9 lbs. or >

Gestational Diabetes Mellitus : 

Gestational Diabetes Mellitus Screening involves a 1 hr. OGTT after consuming 75 gm glucose Abnormal value (>180 mg/dl @ 1 hr. post-prandial) Glucose tolerance reverts to normal in 90% mothers after delivery ~ ½-2/3 will eventually develop Type 2 DM after 5-10 years Usually controlled by diet and exercise; some may require insulin or glyburide (oral secretagogue) Important to lose weight post delivery

SYMPTOMS OF DIABETES : 

SYMPTOMS OF DIABETES TYPE I Glucose cannot enter the cell (hyperglycemia) High blood glucose -> glucose spills into the urine (glycosuria) Is reabsorbed by the kidney until renal threshold is reached (~180 mg/dl) Glucose is hyperosmolar and draws fluid out of cells & tissues and into blood (osmotic effect)  increase in blood & urine production frequent urination (polyuria) with Na & K loss (dehydration). Water must be replaced, thirst is stimulated (polydipsia) Weight loss occurs due to dehydration and breakdown/catabolism of fat and muscle in spite of excessive eating (polyphagia) Energy is wasted as glucose and ketone bodies which are excreted in the urine

SYMPTOMS OF DIABETES : 

SYMPTOMS OF DIABETES TYPE 2 Some glucose enters the cells, but slowly, cells are hungry Hunger (polyphagia)=> overeat => weight gain Hyperinsulinemia helps body store fat from excess kcal Likely to remain overweight D/T elevated insulin and possible defect in gene for leptin. Leptin increases satiety and oxidation of FFA to regulate fat stores (excess calories dissipated as heat). Ketones do not build up in blood and urine (store fat vs. break it down)

CRITERIA FOR DIAGNOSIS OF DIABETES : 

CRITERIA FOR DIAGNOSIS OF DIABETES Fasting (no kcal consumed within the past 8-12 hours); 75 gram glucose challenge; FBG: ≥126 mg/dl OGTT with 2 hour post-load glucose of > 200 mg/dl after glucose load of 75 gm glucose Sx of diabetes (i.e. the three poly’s and/or unexplained weight loss), plus “casual” blood glucose of > 200 mg/dl

FUEL METABOLISM IN THE NON-DIABETIC : 

FUEL METABOLISM IN THE NON-DIABETIC Carbohydrate: readily absorbed as glucose to: Meet energy needs of the body, especially the brain Maintain normal blood glucose levels (need insulin) Stored in the liver and muscles as glycogen Excess is converted to triglyceride (TG) and stored in adipose tissue Fat: primary form is TG Metabolized to energy: TG -> FFA ->Krebs cycle -> ATP OR Stored in adipose tissue as fat, lipogenesis (need insulin for this process; explains difference in weight seen at Dx with Type 1 vs. Type 2 Protein: needed for tissue synthesis and repair Can be converted to glucose in the liver via gluconeogenesis Important energy source during fasting when glycogen stores are depleted

ROLE OF INSULIN & GLUCAGON : 

ROLE OF INSULIN & GLUCAGON INSULIN: Anabolic, functions in fed state to decrease BG by: Stimulating uptake of glucose, by liver & muscle cells, amino acids by muscle & FFA by fat Decreasing synthesis of BG by inhibiting glycogen -> glucose (glycogenolysis) AND by inhibiting protein ---> glucose (gluconeogenesis) inhibits TG ---> FFA (lipolysis) for energy GLUCAGON: Catabolic & functions in the fasting/postabsorptive state to: increase BG by: Enhances glucose production in liver (glycogenolysis), and gluconeogenesis) and fat ->ketone (lipolysis) Prevents glucose uptake by muscle & fat

Insulin : 

Insulin Insulin in the Fed State: Insulin secretion in response to food is biphasic: Stage 1: first 10-20 minutes after eating insulin targets the liver to decrease glucose production (glycogenolysis & gluconeogenesis) Stage 2: >20 minutes insulin allows glucose to enter peripheral cells Tissues that need insulin for glucose utilization - hepatocytes, muscles, & adipocytes Tissues that do not need insulin - brain, nerves, cornea, lens, retina, intestines, kidney, pancreatic beta cells, erythrocytes

Glucagon : 

Glucagon Glucagon in the Fasting State Falling BG levels inhibit insulin release and stimulate glucagon (increases glycogenolysis, gluconeogenesis, & lipolysis) During prolonged fasting or starvation glucagon facilitates ketogenesis. Ketonemia and ketonuria result. Fat is rapidly broken down & exceeds the liver’s ability to completely oxidize it. Results in formation of ketones (acetone, acetoacetic acid and beta-hydroxybutyric acid) Acetone -> fruity breathe The brain can use beta-hydroxybutyric acid for fuel

FUEL METABOLISM IN THE DIABETIC STATE : 

FUEL METABOLISM IN THE DIABETIC STATE Type 1 DM resembles the fasting state with very low insulin levels and elevated glucagon levels resulting in: Muscle and adipose tissue not receiving glucose, level rises Enhanced glucose production by the liver even though BG is elevated D/T glucagon Increased TG breakdown (lipolysis) with FFA release Ketogenesis occurs leading to a drop in pH (diabetic ketoacidosis, DKA)