Diabetes Mellitus And Metabolic Syndrome Lecture Notes PDF

DIABETES MELLITUS AND METABOLIC SYNDROME 10/21/2024 1  DIABETES MELLITUS (DM) Disorder of carbohydrate metabolism High levels of blood glucose Body’s inability to produce or utilize insulin Increased: Morbidity and mortality CVD, renal damage Per...

DIABETES MELLITUS AND METABOLIC SYNDROME 10/21/2024 1  DIABETES MELLITUS (DM) Disorder of carbohydrate metabolism High levels of blood glucose Body’s inability to produce or utilize insulin Increased: Morbidity and mortality CVD, renal damage Peripheral vascular disease Neurological disorders Blindness Amputation  FOUR MAJOR CATEGORIES OF DM Type Abbreviat Characteristic ion Type 1 T1DM Lack of insulin production Beta cells of pancreas destroyed Insulin treatment required Type 2 T2DM 90% of those with DM Insulin resistance Gestational GDM Develops during pregnancy Hormone changes reduce insulin sensitivity Macrosomia Other N/A Pancreatitis, cystic fibrosis, neonatal  EPIDEMIOLOGY In United States >30 million people Parallels obesity increase Sedentary lifestyle Prevalence increases with age Polygenic disorder Environmental factors ETIOLOGY T1DM T2DM Autoimmune destruction of More gradual onset beta cells Insulin resistance Antibodies present Insulin still produced No insulin Sedentary behavior Obesity 10/21/2024 5 INSULIN AND CARBOHYDRATE INGESTION Insulin Produced by beta cells Facilitate glucose movement blood to cells Carbohydrate ingestion: Synchronous rise and fall of glucose and insulin Glucose elevates, so does insulin INSULIN FACILITATES GLUCOSE UPTAKE 10/21/2024 7 CARBOHYDRATE METABOLISM: Process Result OVERVIEW Glucose Used for energy Stored as glycogen Converted to component of lipid molecules Glycogenesis Glycogen formation Primarily in liver and muscle Glycogenolysis Glycogen breakdown When blood glucose levels are low Gluconeogenesi Amino acids + glycerol s of lipids (fats) converted to glucose Liver/kidneys 10/21/2024 8 KETONE FORMATION AND DIABETIC KETOACIDOSIS (DKA) Ketone formation Unable to utilize glucose: Can be due to lack of insulin Free fatty acids: Converted to acetoacetic acid, beta- hydroxybutyric acid, and acetone Known as ketones or ketoacids Diabetic ketoacidosis (DKA) Accumulation of ketones (acidic compounds) Lower blood pH Fruity odor: Breath, saliva, sweat of children with T1DM first present with DKA Critical condition requiring immediate treatment 10/21/2024 9  BLOOD GLUCOSE LEVELS Classification Values (BG = Blood Glucose) Normal blood glucose 70–100 mg/dL (fasting) Hypoglycemia BG 200 mg/dL Impaired glucose tolerance Fasting BG: 100-125 mg/dL (IGT) = “prediabetes” Diabetes Fasting BG: >126 mg/dL Postprandial BG Glucose after eating Greater than 200 mg/dL = diabetes ROLE OF INSULIN Muscle and liver: Glycogenesis Facilitate glucose Adipose: Reduce uptake lipolysis Anabolic hormone Increased insulin level Hyperinsulinism Overcome insulin resistance Too much insulin Hyperinsulinism Resulting in low blood hypoglycemia glucose OTHER GLUCOSE-REGULATING HORMONES Hormone Tissue/Cells of Effect Release Glucagon Alpha cells of Released when BG levels pancreas are low Injectable form in severe hypoglycemia Somatostat Delta cells of Diminishes secretion of in pancreas insulin and glucagon Decreases GI activity, slow absorption Incretins GI tissues GI glucose-regulating hormones (stimulate insulin, slow GI motility) GLP-1 and GIP Cortisol Adrenal cortex Increases blood glucose Epinephrine Adrenal medulla Increases blood glucose GLUCOSE-REGULATING SIGNALS FROM PANCREAS 10/21/2024 1 T1DM: PATHOLOGICAL MECHANISM Autoimmune T-cell mediated attack of beta cells Genetic influence Presenting sign is often DKA Polyuria, polydipsia, polyphagia 10/21/2024 1 T2DM: PATHOLOGICAL MECHANISM Insulin resistance with increased insulin levels Molecular-level mechanisms: Oxidative stress, inflammation, insulin receptor mutation, mitochondrial dysfunction Metabolic syndrome HTN, dyslipidemia, hyperinsulinism, centralized obesity Hyperosmolar hyperglycemia syndrome (HHM) DKA does not normally occur in T2DM Presence of some insulin prevents ketone formation GESTATIONAL DIABETES MELLITUS Hormones of Increase insulin resistance pregnancy Fetal defects, premature Complications: delivery, newborn hypoglycemia, macrosomia 2nd trimester OGTT (oral Screening: glucose tolerance test) GDM normally resolves after Can increase risk for T2DM pregnancy  DIABETES TESTS Test Characteristic Blood glucose Fasting and random Oral glucose 75 g of glucose ingested, measure BG tolerance test (OGTT) Glycated Assess BG levels over the preceding 3 hemoglobin months (A1c) If both fasting BG and A1c are in diabetic range, diagnosis of DM confirmed eAG Average BG over the last few months Islet cell Present in T1DM autoantibodies (ICAs) C-peptide test Indicator of endogenous insulin C-peptide released when pancreas releases insulin Differentiate between T1DM and T2DM  DIABETES TESTS: URINALYSIS Finding Meaning Glucosuria Elevated BG Results in increase filtration of glucose at glomerulus Renal glucose transport maximum exceeded Glucose appears in urine Ketonuria Ketones are produced when glucose cannot be utilized Ketones appear in urine when ketone formation and renal filtration of ketones is elevated More common in T1DM COMPLICATIONS OF DM Both acute and long-term Hypoglycemia and hyperglycemia DKA (T1DM) Acute HHS (T2DM) Blindness, kidney failure, neuropathy, Long-term systemic cardiovascular disease, amputation HYPOGLYCEMIA Excessive exogenous insulin Inadequate food intake BG less than Excessive physical activity 70 mg/dL Infection, illness, drug interaction Compensato Epinephrine, glucagon, ry response activation SNS to raise BG  HYPOGLYCEMIA (CONTINUED_2) Factor Meaning Signs and Activation of SNS: Sweating, hunger, symptoms dizziness, headache, heart palpitations, confusion Management (1) Fast-acting carbohydrates (15 g) Avoid fats (delay glucose absorption) Transient response: Provide meal or snack even if BG greater than 70 mg/dL Management (2) IV glucose Subcutaneous injection: Glucagon Response Repeated episodes of hypoglycemia can blunt compensatory response Autonomic neuropathy: May reduce warning signs Overall Hypoglycemia is a medical emergency  SOMOGYI EFFECT AND DAWN PHENOMENON Somogyi Effect Dawn Phenomenon Morning hyperglycemia Morning hyperglycemia present present Hypoglycemia during sleep Hypoglycemia does NOT occur during sleep Insulin therapy (excessive Nocturnal elevation in growth dosage) or insulin peak during hormone raises BG sleep Compensatory mechanisms Cells utilize less glucose at raise BG night Adjust insulin as needed Adjust medications, exercise, eating patterns  CLASSIC SIGNS OF DIABETES MELLITUS Polydipsia Polyphagia Polyuria High BG increases Cells cannot utilize Increased thirst and plasma osmolarity glucose effectively drinking (polydipsia) Fluid shifts from ICF Lack of insulin Increased renal into ECF Lack of response to glucose filtration insulin Cellular Increase fat/muscle Osmotic diuresis dehydration breakdown Increased thirst Increased appetite Water follows glucose into urine FLUID SHIFTS 10/21/2024 2 FLUID/GLUCOSE IN URINE  ADDITIONAL SIGNS OF DM Blurred vision Accumulation of glucose in aqueous fluid Changes light refraction Fluid/Electrolyte imbalance Fluid shifts ICF to ECF may cause dilutional hyponatremia Electrolyte shifts K+ shifts out of cells  DIABETIC KETOACIDOSIS (DKA) Insulin lacking In presence of insulin DKA does not occur  With insulin, cells utilize glucose for fuel Prevents lipolysis that leads to ketone formation Without insulin (or glucose to use for fuel) More common in T1DM than T2DM Ketone formation occurs Ketones  Strong acids, alter blood pH, metabolic acidosis  DIABETIC KETOACIDOSIS (DKA) Diagnostic criteria Presentation BG >250 mEq/L Nausea pH 7.3 HCO3− >18 mEq/L Blood osmolarity >20 mOsm/L  HYPEROSMOLAR HYPERGLYCEMIC SYNDROME (HHS) (CONTINUED_2) Factor Characteristic Hyperglycemia Cannot adequately facilitate glucose uptake Gluconeogenesis and glycogenolysis further increase BG Hyperosmolarity Elevated BG Osmotic diuresis, polyuria Clinical Can develop insidiously over days to progression weeks Patient Weakness, poor tissue turgor, presentation tachycardia, thready pulse, confusion (25% of patients present in coma) Causes Infection, trauma, noncompliance DM management Treatment Fluids (first) then insulin HYPEROSMOLAR HYPERGLYCEMIC SYNDROME (HHS)  LONG-TERM COMPLICATIONS OF DM Arteriosclerosis Peripheral angiopathy (lack of circulation) Diabetic retinopathy Diabetic neuropathy Autonomic neuropathy Diabetic nephropathy Poor wound healing Immunosuppression LONG-TERM COMPLICATIONS OF DM Factor Effect Arteriosclerosis Myocardial infarction Peripheral angiopathy Limb ischemia Diabetic retinopathy Blindness Diabetic neuropathy Lack of sensation in lower limbs, burning, tingling Autonomic neuropathy Poor autonomic control Diabetic nephropathy Kidney failure Poor wound healing Gangrene Immunosuppression Infections LONG-TERM COMPLICATIONS OF DM LONG-TERM COMPLICATIONS OF DM Complication risk Related to duration of chronic hyperglycemia Genetic susceptibility Chronic hyperglycemia: Damage to the small and large arterial vessels End-organ damage Poor wound healing Macrovascular damage  DM AND ATHEROSCLEROSIS Acute cardiac events 2 to 4 times more likely DM patients Atherosclerosis Large and small arteries Vascular damage Several processes All resulting from hyperglycemia leading to oxidative stress  DM AND PERIPHERAL NEUROPATHY Distal, symmetric polyneuropathy Neural arteries damaged Begins in feet, progresses superiorly Sensorimotor nerves Burning, tingling Pain sensation blunted Signs of injury or serious disease may be missed Silent MI Motor weakness Gait abnormality Mechanics of foot altered Charcot joint DM AND AUTONOMIC NEUROPATHY System Effect Cardiac Tachycardia, hypotension GI Gastroparesis, gastric emptying abnormality Anorexia, nausea Bowel dysfunction Urinary Increased UTI risk Reproductive Erectile dysfunction Temperature regulation Decreased sweating Hyperthermia, dry skin Glycemic control Hypoglycemia Signs and symptoms not as apparent  DM AND SUSCEPTIBILITY TO INFECTION WBC function decreased Increased colonization: S. aureus Candida (yeast) High glucose changes the pH of vagina  Allows Candida to proliferate  Chronic Candida vaginitis may be a presenting feature of diabetes DM AND AMPUTATION Diabetic foot complications Most common cause of nontraumatic lower extremity amputation Peripheral neuropathy, poor circulation, suppressed immune response Increased infection susceptibility Can lead to gangrene and amputation Osteomyelitis (bone infection) DM AND POOR WOUND HEALING 10/21/2024 4 DM AND FOOT CARE Examine foot sensation with light touch Testing of Achilles tendon reflex Sense of toe position Examine for injuries or wounds DM AND RETINOPATHY/BLINDNESS Leading cause of blindness in adults Retinal circulatory damage Signs: Microaneurysms, macular edema “Cotton wool spots” (infarcted regions of retina) Proliferative retinopathy New vessel growth, fragile and may rupture Retinal detachment Regular fundoscopic and ophthalmological exams critical DM AND NEPHROPATHY Renal failure Damage to glomerular capillary Microalbuminuria present Glomerular basement membrane Thicken due to glycosylation end-products Activation of RAAS Compounds problem as BP elevates  DM AND DERMATOLOGICAL Prolonged wound healing and ulcer formations Diabetic skin spots Hyperpigmented areas Acanthosis nigricans Tiny, hyperpigmented, macular lesions Lipoatrophy can occur at insulin injection site DM AND PSYCHOLOGICAL RESISTANCE Depression 2× more common in those with DM Guilt, discouragement, self-blame reported Anxiety related to disease management Psychological insulin Denial and noncompliance resistance Refusal to comply with insulin management  DM AND EATING DISORDERS Young women with T1DM at risk for eating disorder Insulin purging Restrict or skip insulin usage Stimulate lipolysis and weight loss Suspect eating disorder Patients with recurrent DKA Chronically poor glycemic control  DM TREATMENT OVERVIEW Factor Characteristic Blood glucose Both hyper- AND hypoglycemia control Glycemic control Primary goal Decrease risk for all complications Reduce CVD risk Lipid panels LDL 60 mg/dL; TGs