Endocrine Patho Exam 2

Diseases of the Digestive Pancreas Condtion Pancreas Divisum Annular Pancreas Ectopic (Heterotopic) pancreas Descirption ●​ Most common congenital anomaly ●​ Results from the failure of the two embryonic pancreatic ducts to fuse ●​ Leads to the formation of two separate ductal systems – each draining into the duodenum through the major and minor papillae ●​ Chronic pancreatitis develops in up to 25% of patients ●​ ●​ ●​ ●​ ●​ ●​ Congenital deformity The head of the pancreas encircles the duodenum May cause duodenal obstruction Can constrict the duodenum and block or impair the flow of food to the rest of the intestines Patients frequently have other congenital anomalies, including duodenal atresia Increased incidence in trisomy 21 ●​ Embryologically misplaced but histologically normal pancreatic tissue that has come to rest in an abnormal place ●​ No vascular or anatomical connections to the pancreas ●​ Most common sites include the stomach, duodenum, and the proximal jejunum ●​ May be functionally active and secreting, causing local ulceration ●​ May give rise to benign or malignant pancreatic tumors Pancreatitis Acute V Chornic Acute Pancreatitis (pseudocyst) Overview ●​ Sudden inflammation of the pancreas ○​ Varying presentation depending on the level of inflammation and necrosi ●​ Quick onset of symptoms ○​ Severe epigastric pain radiating to the back, N/V/D, anorexia, fever, tachycardia, shock, respiratory distress ●​ Increasing incidence globally = increasing incidence of pancreatic cancer Pathophysiology ●​ Acinar cell injury and duct obstruction leading to leaking pancreatic juices and consequent damage to surrounding tissues ●​ Necrotizing pancreatitis ●​ Multiple areas of edema and congestion ●​ Necrosis and bleeding ○​ Leading to acute hemorrhagic pancreatitis ●​ Pseudocyst ○​ A common outcome of acute hemorrhagic pancreatitis formation of a fibrous cyst in the pancreas ●​ Destruction of peripancreatic fat tissue ○​ Foci of saponification around the pancreas ●​ Malabsorption – due to lack of pancreatic enzymes ●​ 5% mortality rate Causes ●​ **Gallstones (#1) – duct obstruction ●​ **Alcoholism (#2) ○​ May occur with 4-5 drinks per day over 2-3 weeks ○​ Many alcoholics have long-standing subclinical pancreatitis that may flare into acute pancreatitis ○​ Alcohol irritates the duodenum restricting the flow of pancreatic juices ○​ Alcohol also stimulates pancreatic enzyme secretion ●​ Hypertriglyceridemia (#3) ●​ NSAID use, Pregnancy, Obesity ●​ Acute ischemia – shock, thrombosis ●​ Infection (mumps, coxsackievirus, rubella, CMV, EBV, HIV), Ascaris ●​ Blunt trauma ●​ Diuretics, antiretrovirals, some immunosuppressive agents (ie azathioprine), some antineoplastic agents, estrogens ●​ Renal failure ●​ The prevalence of AP among patients with AIDS is 1000x greater than that of the general population ●​ IBD ●​ Hypercalcemia ●​ Idiopathic ●​ Smoking - - 2.5 fold risk Signs and Symptoms ●​ Acute onset ●​ Nausea, vomiting, severe abdominal pain (right upper quadrant), abdominal distension, pain radiating to the back, constipation or diarrhea ●​ Quick onset of symptoms ●​ Severe epigastric pain radiating to the back ●​ N/V/D, anorexia ●​ Fever, tachycardia, ●​ Shock, respiratory distress Associated Outcomes ●​ Multiple areas of edema and congestion ●​ Necrosis and bleeding ○​ Leading to acute hemorrhagic pancreatitis ●​ Pseudocyst ○​ A common outcome of acute hemorrhagic pancreatitis formation of a fibrous cyst in the pancreas ●​ Destruction of peripancreatic fat tissue ○​ Foci of saponification around the pancreas ●​ Malabsorption – due to lack of pancreatic enzymes ●​ 5% mortality rate pancreatitis ●​ Disease may progress rapidly to vascular collapse, shock, renal failure, and ARDS Acute hemorrhagic pancreatitis is a medical emergency ●​ Grey-Turner sign (hemorrhagic discoloration of the flanks) ●​ Cullen sign (hemorrhagic discoloration of the umbilicus) Lab values ●​ Amylase – rises and falls quickly (non-specific) ●​ Lipase – slow to rise and fall (pancreatic specific) ●​ Elevated serum amylase and lipase w/in 24-72 hours is diagnostic for ●​ Bilirubin – elevated with obstruction ●​ Hyperglycemia – damage to islet cells ●​ CT scan is the most reliable imaging modality for diagnosis ●​ Reversible but recurrent acute attacks may produce irreversible chronic disease Ranson Criteria ●​ Determines mild vs severe AP ●​ ◦ When 3 or more features are ●​ present on admission, a severe course complicated by pancreatic necrosis can be predicted up to 80% of the time ●​ Chronic Pancreatitis ●​ Repeated episodes of acute pancreatitis ●​ Destroys and scars the pancreas ●​ Symptoms ○​ Persistent abdominal pain, steatorrhea (secondary to malabsorption), DM ●​ Diagnosis – American College of Gastroenterology ○​ Characteristic abdominal pain plus one of the following ○​ Characteristic cross-sectional imaging (CT or MRI) or ERCP – pancreatic calcifications or pancreatic duct irregularities ●​ Secretin pancreatic function testing with peak bicarbonate < 80 mEq/L ●​ Histological confirmation of CP ●​ Pancreatic inflammation ●​ Damage to exocrine, endocrine, and ductal cells ●​ Abdominal pain, exocrine and endocrine inefficiency ●​ Persistent pathologic response ●​ 1/3 of AP progresses to CP ●​ Pancreatic tissue is replaced by fibrous scar tissue and calcifications ○​ Small and densely fibrotic ●​ If enough beta cells are destroyed the patient will become diabetic ●​ Genetic, metabolic environmental risk factors ●​ Majority of cases are related to chronic alcoholism – 80% of cases ○​ Alcohol causes hypersecretion of pancreatic enzymes, which results in the precipitation of “protein plugs” in small branches of pancreatic ducts ●​ A likely manifestation in cystic fibrosis secondary to thick secretions causing ductal obstruction ●​ Chronic Renal Failure is linked to chronic pancreatitis ●​ Autoimmune chronic pancreatitis ○​ Occurs in association with other autoimmune and sclerosing disorders (ie IBD) ◦ Presentation Atlanta Criteria ●​ Determines mild vs severe AP ◦ At least 2 of the following ○​ Characteristic abdominal pain ○​ Serum amylase or lipase > 3x normal ○​ CT or MRI characteristic of AP ●​ Obscure, nagging upper abdominal pain radiating to the back Lab values ●​ Amylase and lipase – less valuable in diagnosing chronic disease ●​ May be normal or low if injury has destroyed most of the pancreas Radiographic imaging ●​ CT scan ○​ Diagnostic for chronic pancreatitis ○​ Demonstration of calcium deposits and cysts Neuropathic pain ●​ Structural or functional changes in the nerves ●​ Due to inflammation and fibrosis Diseases of the Digestive Pancreas Cont. Acute V Chornic Overview Pathophysiology Causes Signs and Symptoms Associated Outcomes Adenocarcinom a of the Pancreas Pancreatic Cancer Whipple Procedure ●​ 4% 5-year survival rate ●​ 4th most common cancer in men ●​ Following lung, prostate, and colon cancers ●​ Most common type of pancreatic cancer ●​ Cancer of exocrine cells (enzyme production) of the pancreas ●​ 9:10 people with pancreatic cancer ●​ Imaging: Endoscopy, MRI, ultrasound ●​ ●​ Genetic alterations of Pancreatic Intraductal Neoplasia (PanIN) ●​ Telomere shortening and KRAS activation ●​ p53 inactivation, BRAC2 presence ●​ Cyclin-dependent kinase gene alteration ●​ Overactivity of epidermal growth factor (EGF) and HER2 ●​ Deletions in chromosome 18 are present in 90% of pancreatic cancers ●​ Risk factors ○​ Chronic alcohol use, smoking, high caloric intake, DM, chronic pancreatitis, obesity, familial pancreatic cancer ○​ Smokers have twice the risk as non-smokers ●​ Pancreatoduodenectomy ●​ An operation to remove a portion of the pancreas, a portion of the duodenum, the gallbladder, and part of the bile duct ●​ The remaining organs are reattached to allow for food digestion ●​ Insidious onset ○​ Few symptoms until it has progressed beyond resection for cure ●​ Jaundice ○​ Tumors in the head of the pancreas (most common site) may cause jaundice by blocking the common bile duct ●​ Upper abdominal pain or back pain are presenting symptoms ●​ Unexplained weight loss ●​ Trousseau sign - migratory thrombophlebitis (seen 10% of patients) ●​ Courvoisier sign – acute, painless gallbladder dilation w/ jaundice due to common bile duct obstruction ●​ Metastasis ○​ Local lymph nodes and the liver are common sites ●​ CA19-9 Elevation ○​ Tumor marker for pancreatic cancer – not a screening test ●​ The Hormonal Pancreas ⇒ Small fraction of pancreatic mass Composed of islets of Langerhans ⇒ Clusters of cells not connected to ducts, Hormones are secreted into interstitial space and, then picked up in the bloodstream ⇒ Alpha cells (25%) — Secrete glucagon ⇒ Beta cells (70%) — Secrete insulin, amylin ⇒ Delta cells (5%) — Secrete somatostatin Condition Overview Pathophysiology Causes Carcinoma of Endocrine Glands ●​ Pancreatic Neuroendocrine Tumor (PNET or PanNET) ○​ Component of MEN1 ●​ Rare Islet cell tumors ●​ Insulinomas are most common ●​ Symptoms are dependent on the cell of origin ●​ May be hormonally active ○​ Gastrin, glucagon, insulin, somatostatin, VIP – vasoactive intestinal peptide​ ZollingerEllison Syndrome ●​ Tumors located in the pancreas or duodenum ●​ Secrete excess gastrin, which stimulates increased gastric acid production ●​ Involves the ulceration of the stomach and esophagus ●​ May occur sporadically or be associated with MEN1 syndrome Islet Cell Transplant ●​ Experimental treatment for Type I diabetes ●​ Limited success ●​ Matched donor’s (deceased) pancreatic cells are infused into the patient's liver through the portal vein ●​ Immunosuppressive therapy is necessary to prevent rejection Signs and Symptoms Associated Outcomes ●​ Diarrhea, ulceration, pain, weight loss Pancreatic Hormones — Diabetes Insulin Insulin entering the cells: Insulin Dependent Insulin Independent Insulin Secretion Insulin Activities This stimulates ●​ Glucose binds to GLUT 2 receptors on the plasma membrane of beta cells ●​ Signaling exocytosis of insulin and amylin ●​ Alerts cells that sufficient glucose is present for them to take it up freely Glucagon ●​ Released from alpha cells of the pancreas when glucose concentrations fall Incretins ●​ Hormones released from the small intestine in response to glucose ingestion/absorption Amylin ●​ Amylin is secreted by pancreatic beta cells in response to food intake and elevated blood glucose concentrations ●​ Prohibits cells from using glucose when levels are low (preserve for vital organs) ●​ GLUT 4 receptors - only activated when insulin is present ●​ Cells in the brain, heart, kidneys, digestive tract lining, and RBCs are insulin- independent (can use glucose w/o an “insulin key”) ●​ GLUT 1 & GLUT 3 receptors ○​ Always present and able to transport glucose into the cell Primary effects ●​ Stimulation of glycolysis in skeletal muscles ●​ Stimulation of lipolysis in adipose tissue ●​ Stimulation gluconeogenesis in the liver (from amino acids) Primary effects ●​ Work to enhance insulin release, slow GI transit, decrease glucagon release Primary effects ●​ Amylin slows gastric emptying and suppresses glucagon secretion ○​ w/o amylin, glucose from food enters the bloodstream more quickly ●​ Amylin modulates appetite, sending a satiety signal to the brain ○​ Weight loss ●​ Basal insulin release ○​ Small amount of insulin released throughout the day and night ○​ Enough to run the body ●​ Meal insulin release ○​ Blood glucose peaks within 30 minutes after starting a meal ○​ Stored insulin is released immediately (Phase I) ●​ If the glucose concentration rises to over 100mg/dL ○​ Beta cells start secreting more insulin (Phase 2 ●​ Blood glucose levels should return to normal (85mg/dL) 1-2 hours after the meal ●​ Acceleration of glucose intake ●​ Acceleration of glucose utilization and enhanced ATP production ●​ Stimulation of glycogen formation in skeletal muscle and liver cells ●​ Stimulation of amino acid absorption and protein synthesis ●​ Stimulation of triglyceride formation in adipose tissue ●​ Suppression of fat as an energy source Store extra glucose as glycogen vs lipid? Lipids ●​ Insulation; cushioning ●​ Store twice as many calories as glycogen Glycogen ●​ Readily accessible – easy to change to glucose ●​ Hydrophilic – draws in water ○​ The body would need to weigh 500+ pounds to store all reserve calories as glycogen Incretin Peptides ●​ Two primary incretin peptides ○​ Glucagon-like peptide-1 (GLP-1) ○​ Gastric inhibitory peptide (GIP) ●​ Incretins are inactivated by ○​ Dipeptidyl peptidase-4 (DPP-4) ○​ Breaks down GLP + GIP Clinical Application: ●​ All Type 1 DM and many Type 2 DM patients are amylin deficient Diabetes Mellitus ⇒ A disorder of insulin action and secretion that results in hyperglycemia ⇒ Glucosuria, Polyuria, polyphagia, polydipsia ⇒ “ominous octet” • Decreased insulin production • Increased glucagon secretion • Central dysregulation of appetite control • Insulin resistance • Impaired incretin effect • Hepatic glucose overproduction • Increased renal reabsorption of glucose • Increased lipolysis Type Type 1 DM Pathophysiology ●​ Autoimmune destruction of beta cells ●​ Inadequate insulin production ●​ Exogenous insulin administration is necessary ●​ Absolute deficiency of endogenous insulin production ○​ Autoimmune destruction of beta cells ○​ Early Type I islets are infiltrated by T-lymphocytes ○​ Anti-insulin antibodies also seen in some patients ●​ HLA-DR3 or HLA-DR4 genes on chromosome 6 are seen in 95% of patients with Type I DM ●​ Patients become diabetic when >80% of the beta cell population is lost Causes/Risk Factors ●​ Autoimmunity, virus, injury ⇒ Accumulation of lymphocytes Diagnostics ●​ Diagnosed based on antibody presence of ○​ Pancreatic autoantibodies ○​ Islet cell autoantibodies ●​ Stimulated C-peptide test ○​ Measures C-peptide released from the pancreas ○​ C-peptide is released from the pancreas when insulin is made ○​ C-peptide is longer-lasting, which makes it easier to measure than insulin ○​ Used to differentiate T1 and T2 DM ○​ C Peptide absence Signs and Symptoms ●​ Onset of symptoms may be gradual or abrupt ●​ Most commonly diagnosed between 5 and 20 years old ●​ Weight loss is seen as muscle proteins are catabolized Complications ●​ Prone to diabetic ketoacidosis ○​ Accumulation of ketone bodies with lipid metabolism Type 2 DM ●​ Sufficient/insufficient insulin production ●​ Defective insulin receptors or insufficient glucose receptor formation ●​ The current-day care of T2DM is directed at lowering glycemia to ameliorate associated morbidity ○​ Reduced glucotoxicity allows beta cells to function better and more effectively ○​ We are currently focused on treating the symptom – not the cause ●​ Primary defect is peripheral cell resistance to insulin ○​ Some endogenous insulin production ○​ Resistance in peripheral tissue ●​ Seen up to 10 years before diagnosis ●​ Islets are gradually replaced by amyloid tissue ○​ No more endogenous insulin production TDDM in Pediatrics Prediabetes ●​ Characterized initially by HIGH levels of ●​ insulin and normal (or slightly increased) fasting glucose levels ●​ Overworked beta cells become exhausted ●​ Insulin production decreases (to normal or below) and glucose levels rise ●​ Pre-DM is reversible with 7% weight loss ●​ Reduction of DM onset with weight loss – 56% ●​ Diet and exercise-related ●​ > 60% of patients have a + FH ○​ Strong Genetic Component ●​ Obesity ●​ Drug therapy ○​ Corticosteroids ●​ Endocrine disease ○​ Cushing diseases ○​ Polycystic Ovarian Disease ●​ 5 nights of sleep restricted to 4 hours per night results in ○​ A 24% decrease in insulin sensitivity ○​ A 30% decrease in the acute insulin response to glucose ●​ Peripheral Resistance to Insulin is secondary to other conditions ●​ ADA recommends DM screening starting at age 45 then Q 3 years ●​ Screen more frequently in patients who are overweight, obese, +FH DM, hyperlipidemia, CVD, PCOS, gestational DM, physical inactivity ●​ USPSTF recommends DM screening for all adults at 35-70 with BMI >/= 25 ADA Screening Recommendations: ●​ Screen asymptomatic high-risk youth for T2DM Q3 years beginning at 10-year-old ●​ ADA considers children at high risk if ○​ They are overweight or obese ○​ Have a FH of T2DM ○​ Have signs of insulin resistance ○​ Maternal history of gestational DM ●​ Impaired Fasting glucose ●​ > 110 mg/dL ●​ Patient’s risk of developing Type II is dramatically increased Diabetes Distress ●​ Affects 1:5 people with diabetes – more common with insulin-dependent DM ○​ Sometimes mistaken for depression ●​ Associated with adverse outcomes ○​ Suboptimal self-management; Elevated A1c ○​ More frequent severe hypoglycemia; Impaired quality of life ●​ May lead to diabetes burnout ○​ Disengagement from self-care tasks; Unhealthy or uncontrolled eating ●​ ●​ ●​ ●​ ●​ ●​ ●​ ●​ Lifestyle Component 40+ years old Central obesity BMI >/= 30 HTN Dyslipidemia Atherosclerosis High serum insulin concentration ●​ Solving/treating more effectively the obesity issue is the single greatest challenge and would be the most effective means of preventing and treating diabetes ●​ Mutations in genes that encode for adipokines, elevations in TNF, and subnormal serum concentrations of leptin and adiponectin may contribute to the development of insulin resistance ●​ LT complications Complications: ●​ Blindness, ESRD, amputation, CVD ●​ The progression of disease in children is more rapid and more severe than in adults ●​ Obese adolescents with T2DM may have diminished cognitive performance and brain abnormalities, including reduced white matter and an increased CSF space ●​ Healthcare costs are 2x more than non-DM patients Who Should Be Screened? ●​ Testing should be considered in overweight or obese patients (BMI > 25kg/mm3) who have one or more of the following: ○​ First-degree relative with DM ○​ High-risk race/ethnicity (African American, Latino, Native American, Asian American, Pacific Islander) ○​ History of CVD, HTN (or on therapy for HTN) ○​ HDL levels < 35 mg/dL, or triglycerides > 250 mg/dL ○​ History of PCOS, acanthosis nigricans ○​ Physical inactivity ○​ Risk-taking behaviors ○​ Non-attendance at clinic appointments ●​ Identify signs of burnout – help the patient to manage ○​ Avoid labeling the patient as difficult, non -compliant or unmotivated Consequences of DM ●​ Peripheral limb necrosis, ulceration, infection ○​ Leading cause of amputation in the US ○​ 20x more likely to be hospitalized for LL amputations ●​ Increased infection risk ○​ Blood glucose concentration > 250mg/d causes white cell dysfunction ●​ Degenerative blockages in cardiac circulation ○​ Accelerated hypercholesterolemia ○​ 3-5X higher MI risk ○​ 3x more likely to be hospitalized with CV disease ●​ Diabetic neuropathy ●​ Begins with damage to small vessels that supply the organs ●​ Diabetic retinopathy ○​ Non-proliferative and proliferative retinopathy ●​ Cataracts ○​ Accelerated formation ○​ Glycosylation of lens proteins ●​ Diabetic nephropathy ○​ DM is the most common primary diagnosis in persons with chronic kidney failure – 12 x more likely to be hospitalized for ESRD ○​ Glycosylation of proteins in the capillary basement membrane, microaneurysms, glomerular hypertension, and chronic inflammation contribute to this process ○​ Kimmelstiel Wilson nodes are present on biopsy – diagnostic for diabetic nephropathy ○​ HTN, hyperglycemia, and high triglyceride levels are associated with an elevation in the albumin-to-creatinine level ●​ Most common cause of ESRD ●​ Most common cause of blindness ●​ Most common cause of amputations ●​ Newly recognized complications ●​ Increased risk for dementia, cancer, sleep apnea and poor outcomes of COVID-19 Short Term Complications of DM ●​ Glycosuria ○​ Wasting of calories, electrolytes, water ●​ Polydipsia & polyuria ○​ Dehydration, electrolyte imbalance ○​ Osmotic diuresis - Glucose in the glomerular filtrate that exceeds a max renal tubular threshold of 180mg/dL cannot be reabsorbed ●​ Polyphagia ○​ Cells cannot use glucose DKA ●​ Arises b/c the body must burn fat ●​ Fat is broken down into fatty acids ●​ Fatty acids are metabolized by the liver to ketones ●​ Accumulation of ketones lowers blood pH ●​ Unbound ketones are excreted by the kidneys and blown off by the lungs ○​ Respiratory compensation ●​ BG > 250mg/dL ●​ Serum bicarbonate < 18mEq/L ●​ Acute onset – hours ●​ Most often assoc. w/ Type I ●​ Even mild upsets can rapidly push a Type I DM patient into ketoacidosis ●​ Vomiting, diarrhea ●​ Acidosis ○​ Mild: pH decreased 7.25 - 7.30 bicarbonate to 15–18, patient is alert ○​ Moderate: pH 7.00–7.25, bicarbonate 10–15, mild drowsiness may be present ○​ Severe: pH below 7.00, bicarbonate below 10, stupor or coma may occur ●​ Kussmaul respiration ○​ Rapid, deep breathing as the lungs work to expel CO2 and ketones ●​ Glycosuria, ketonuria, osmotic diuresis, volume depletion ●​ Altered mental status, hypothermia, hypotension ●​ Tachycardia, tachypnea, polyuria, polydipsia Hyperosmolar Hyperglycemic Syndrome (HHS) ●​ BG levels 600-800 mg/dL ●​ Ketoacidosis does not occur because enough insulin is present to prevent excessive fat metabolism ●​ In the absence of acidosis, the GI symptoms are generally not present therefore, patients do not seek medical attention – high blood glucose levels can result Long Term Complications of DM ●​ Can occur if water loss is severe ○​ 12 L/day lost when blood concentrations are very high ●​ Most likely seen in the elderly with T2DM ○​ Less aware of fluid status ●​ Not associated with rapid respiration ●​ ●​ ●​ ●​ ●​ ●​ ●​ Slower onset – days Focal seizures or motor abnormalities Flaccidity, depressed reflexes, tremors, N/V, altered mental status Hyperviscosity and increased risk of thrombosis Polyuria, polydipsia Tachycardia Coma Accelerated atherosclerosis ●​ MI, stroke ●​ DM is one of the most significant risk factors for ischemic stroke, especially in individuals < 65 Peripheral vascular disease ●​ Retinopathy, renal insufficiency (diffuse glomerulosclerosis) ●​ Peripheral neuropathies, gangrene Stroke Pathogenesis ●​ Intracellular acidosis resulting from hyperglycemia increases lactate, leading to glial and neuronal membrane damage due to reactive oxygen species generation and impaired vasodilation ●​ 35+% increased risk of AF in DM patients = increased stroke risk Increased infection risk ●​ Pneumococcal pneumonia ●​ TB ●​ Infections of the skin and urinary tract ●​ Foot infections Sexual Dysfunction ●​ Primarily seen secondarily to vascular changes, plaque build- up and ischemia ●​ Obesity seen in T2DM can be a factor related to decreased testosterone levels in men Diabetic foot infections ●​ 2-6% risk of foot infections among all pts with DM ●​ Once an ulcer is established – 50-60% of patients progress to infection ●​ Once infection is diagnosed – 15% require amputation w/in 1 year ●​ Organisms – S. aureus, group B strep, many enteric-gram negative rods, Pseudomonas Vascular Disease ●​ Other abnormalities stem from disturbances in the vascular system ●​ Lower limb amputation is 200 x more common in diabetic ●​ In large vessels atherosclerosis is accelerated ○​ Stroke, MI, poor wound healing ●​ In small vessels ○​ Hyaline arteriosclerosis ○​ Nephropathy, retinopathy Kidney Disease ●​ Diabetic nephrosclerosis ○​ Diffuse glomerulosclerosis ○​ Most common cause of renal failure in US ○​ Increased incidence of pyelonephritis and cystitis ●​ Effects of ANGII ○​ Pro-inflammatory, pro-oxidant, platelet adhesion ○​ Endothelial damage; ultimately renal dysfunction ○​ Use of ACEIs and ARBs ■​ Recommended for patients with HTN and DM ■​ Recommended for patients with albuminuria Eye Disease ●​ Blurred vision ○​ Develops when the lenses are exposed to hyperosmolar fluids ●​ Blindness associated with cataracts,​glaucoma, optic nerve damage ●​ Diabetic retinopathy ○​ Proliferative retinopathy ■​ Exudates, hemorrhages, edema, angiogenesis, small aneurysms, scarring ○​ Leading cause of blindness in people under 60 yo in the US ■​ Some conflicting evidence to recommend use in normotensive patients with DM - Low dose most advantageous Brain and Peripheral Nerve Disease ●​ The entire peripheral nervous system is affected by diabetes ○​ Motor, sensory, autonomic ○​ Sensory function is affected first and more than other functions ●​ Initial symptoms ○​ Nerve irritation, pain, paresthesias ●​ Later symptoms ○​ Loss of fine touch sense, pain, proprioception ●​ Diabetic foot ulcers ○​ Patients are unaware of injury until severe ●​ Charcot Joint (Neuropathic Arthritis) ○​ Impaired sensation from lower limb joints ●​ Patients damage joints w/o realizing pain, leading to continuing damage ●​ Foot Drop ○​ Can indicate palsy of single nerves ●​ Postural hypotension ○​ Lack of autonomically controlled vascular tone ●​ Erectile dysfunction ●​ Bowel and bladder control abnormalities ●​ Gastroparesis ●​ Stroke ●​ Occlusion of cerebral arteries ●​ Cerebral necrosis ●​ Secondary to hyperglycemia Infants + Women with DM Fetal Complications ●​ Hyperglycemia ○​ Movement of maternal glucose across the placenta ●​ Hyperinsulinemia ○​ Hyperplasia of fetal islet cells – increased insulin production Neonatal hypoglycemia ○​ Increased metabolic rates increased hypoxia ●​ Increased hypoxia ○​ Increased erythropoiesis – polycythemia – low iron stores ○​ Increased SNS demand – cardiac demand – cardiomyopathy ●​ Delayed lung development – respiratory distress ●​ Macrosomia ○​ > 90th for gestational age ○​ Difficult delivery – birth injuries Pregnancy ●​ Increasing incidence due to increasing obesity rates ●​ 1/3 of gestational DM will develop Type II diabetes w/in 10 years ◦ ●​ Infants born to diabetic mothers tend to be larger than infants of comparable gestational age ○​ Maternal glucose crosses the placenta ○​ Causes stimulation of fetal insulin ○​ Accelerated fat deposits and growth Monitoring Possible Outcomes ●​ Babies who were conceived and born during the period of sugar rationing in the UK were less likely to develop HTN (20%) and DM (35%) as adults ●​ During rationing, adults were limited to 40g (1/4 cup) of sugar per day (equal to 1 can of Coke) ●​ Limiting sugar during the first 1000 days after conception may reduce a child’s risk of DM and HTN in adulthood Glycosylation ●​ Attachment of glucose to proteins ○​ Hgb, albumin, lipoproteins, lens proteins, collagen, cell membrane proteins ●​ Useful indicator of glucose levels over time ○​ Glycohemoglobin (Hgb A1C) ○​ Attachment of glucose to hemoglobin ○​ An index of average blood sugars over the prior 3 months ○​ Ideal levels in DM 6-7 ●​ Prediabetes risk for DM ○​ Hgb A1C level and future risk of diabetes Fructosamine ●​ Attachment of glucose to albumin ●​ Reflects the average blood glucose over the prior 2-3 weeks ●​ Utilized less than HgbA1C ●​ May be useful in gestational diabetes Blood Glucose level ●​ ●​ ●​ ●​ Normal fasting 70-110mg/dL Impaired fasting 111-125mg/dL Diabetes (fasting) >125mg/dL Impaired glucose tolerance 140-199 mg/dL ○​ 2 hours after meal ●​ Diabetes > 200 mg/dL ○​ 2 hours after meal Hypoglycemia ●​ Results from hyperinsulinemia (exogenous insulin, an insulin-pancreatic tumor, or excessive oral diabetic medication) ●​ Or alteration in glucose counterregulation ●​ Advanced age ●​ Long duration of insulin therapy ●​ Neuropathy ●​ Low health literacy ●​ Cognitive impairment ●​ ●​ ●​ ●​ Trembling, tingling Nausea, palpitations, weakness Sweating, hunger Anxiety, difficulty concentrating, HA, dizziness ●​ Drowsiness, fainting ●​ Vision changes ●​ Coma, death ●​ Repeated episodes of hypoglycemia result in a defect of insulin/glucagon control – hypoglycemia-associated autonomic failure (HAAF) ●​ Characterized by both defective glucose counterregulation and hypoglycemia unawareness ●​ Tight glucose control and avoidance of hypoglycemia can reverse HAAF ●​ Nocturnal hypoglycemia ○​ Sleep impairs the counter-regulatory response to hypoglycemia in individuals with or without DM Hyperglycemia Somogyi Effect (phenomenon) ●​ Rebounding high blood sugar in response to low blood sugar (with insulin administration) ●​ Can occur any time during the day – most commonly overnight ●​ If prolonged hypoglycemia is untreated, then stress due to low blood sugar results in glucose rebound ●​ The body responds by releasing glucagon, epinephrine, and cortisol Dawn Phenomenon ●​ Normal morning rise in blood sugar secondary to the surge in glucagon and cortisol during nighttime fasting ●​ No insulin or decreased insulin sensitivity to counteract the glucose surge ●​ Resolves with an increase in evening insulin dose ●​ Suspected when blood glucose numbers are higher after the insulin dosage has been raised, particularly in the morning