Fm 6 Flashcards
Pathophysiology of Diabetes 1&2
Type 1 diabetes mellitus
The pancreas is damaged, and the beta cells don’t produce enough insulin. (Immunologic etiology)
Type 2 diabetes mellitus
The body is unable to recognize the insulin produced by the pancreas and use it properly (insulin resistance). Increased beta cell insulin secretion may initially compensate, but over time, beta cells fail.
Complications
Both types of diabetes cause the same end-damage. High blood glucose eventually affects blood vessels and therefore organs throughout the entire body. The heart, brain, kidneys, and eyes and the nerves that control sensation and autonomic function are affected.
Remember: High blood pressure, which many patients with diabetes have, makes the vascular disease much worse.
Diabetes: Common Manifestations of End-Organ Damage 4
Cardiovascular disease, including both coronary heart disease and cerebrovascular disease
The leading cause of death in patients with diabetes. People with diabetes are 2-4 times more likely to have heart disease or stroke than people without diabetes. Patients with diabetes who have a myocardial infarction have worse outcomes than patients without diabetes, and a diagnosis of diabetes is considered equivalent in risk to having had a previous myocardial infarction. Management of cardiovascular risk factors so commonly found in diabetes is therefore essential in preventing morbidity and mortality in these patients.
Retinopathy
Diabetes is the most common cause of new cases of blindness among adults of working age. Five years after diagnosis of type 2 diabetes, patients with more severe or uncontrolled disease that requires insulin have a 40% prevalence of retinopathy while those on oral hypoglycemic agents have a 24% prevalence. After 15 years of diabetes, almost all patients with type 1 diabetes and two thirds of patients with type 2 diabetes have background retinopathy. By the time the patient’s vision is affected, substantial retinal damage may have already occurred. Proliferative retinopathy is prevalent in 25% of the diabetes population with 25 or more years of diabetes.
Neuropathy
Neuropathy is a heterogeneous condition that is associated with nerve pathology. The condition is classified according to the nerves affected. The classification of neuropathy includes focal, diffuse, sensory, motor and autonomic neuropathy. The prevalence of neuropathy defined by loss of ankle jerk reflexes is 7% at 1 year increasing to 50% at 25 years for both type 1 and type 2 diabetes.
Nephropathy
Nephropathy is common in diabetes. 20-40% of people with diabetes develop diabetic nephropathy. Diabetes was listed as the primary cause of kidney failure in 44% of all new cases in 2011.
While hyperthyroidism is not an end organ result of diabetes, this hypermetabolic state can unmask underlying glucose intolerance, and adversely affect glucose control and lipid management in patients with diabetes. Hypothyroidism can cause fatigue, depression, and dyslipidemia, all of which complicate management of diabetes.
Acute Diabetic Decompensations (DKA and HHS
Type 1 Diabetes
In patients with type 1 diabetes, without sufficient insulin, blood sugar runs high, and diabetic ketoacidosis (DKA) can develop.
Type 2 Diabetes
Type 2 patients with hyperglycemia more often develop hyperosmolar hyperglycemic state (HHS) .
Typically it is the patient with type 1 diabetes who is most at risk for developing DKA; however, patients with type 2 diabetes can also develop DKA. This happens because over time, type 2 diabetes starts to resemble type 1 diabetes as pancreatic function dwindles and patients with type 2 diabetes may begin to require insulin. If the insulin deficiency is severe enough, a patient with type 2 diabetes may produce ketones and develop hyperglycemia. For example, an elderly patient with longstanding type 2 diabetes who becomes acutely ill with pneumonia could easily develop DKA.
Hyperosmolar Hyperglycemic State (HHS) vs Diabetic Ketoacidosis (DKA) 4
Hyperosmolar hyperglycemic state (HHS) should not be confused with diabetic ketoacidosis (DKA) - the other severe diabetic decompensation. Both HHS and DKA are life-threatening conditions that require prompt management.
HHS
DKA
Mortality
Increases with increasing age and serum osmolality. The average mortality rate in many studies is 15%, but can be as high as 20-30% in the presence of significant infection.
Mortality rate is roughly 2% for patients under 65 years old, but as high as 22% for patients over 65 years old.
Serum pH
Not a metabolic acidosis. Serum pH is generally > 7.3, with a bicarbonate > 15 mEq/L (>15 mmol/L).
Metabolic gap acidosis associated with a pH <7.30.
Plasma glucose
Plasma glucose levels are usually >600 mg/dL.
Lower plasma glucose levels, i.e., 250 mg/dL.
Ketones
Ketones are absent or only mildly elevated because type 2 diabetes patients usually have enough endogenous insulin to suppress or greatly limit ketogenesis.
Ketosis
Physical findings of HHS:
HHS is characterized by severe dehydration. A profound fluid deficit is usually present, in excess of 9 L on average in adults. Serum osmolality usually exceeds 320 mOsm/kg. Fluid replacement is a key component of treatment.
Precipitants of HHS:
Infections, like pneumonia and urinary tract infections, accompanied by a decreased fluid intake are the most common underlying causes of HHS. Other acute conditions like stroke, MI or pulmonary embolism may also precipitate HHS.
2 things to not forget to ask when dealing with DM
Dentist
When diabetes is not controlled properly, high glucose levels in saliva may help bacteria that attack tooth enamel thrive. Going to the dentist and brushing your teeth helps remove decay-causing plaque which can result in cavities and gum disease.
It is also important to go to the dentist regularly because gum diseases and fungal infections appear to be more frequent and more severe among diabetics due to immunosupression.
Additionally, periodontal disease can increase the risk of heart trouble.
Depression
Screening Recommendations for Type 2 Diabetes ada vs usfptf
American Diabetes Association Recommendations
Overweight or obese patients (body mass index 25 kg/m2) who have one or more of the following additional risk factors:
Physical inactivity
Race/ethnicity (e.g., Native American, Pacific Islander, Latino, African American, Asian American)
First-degree relative with diabetes
Previously diagnosed impaired fasting glucose (100-125 mg/dL) or impaired glucose tolerance (2-hour plasma glucose > 140 mg/dL following a 75 gram glucose load)
Hypertension (Blood pressure > 140/90 mmHg)
HDL cholesterol < 35 mg/dL and/or triglycerides > 250 mg/dL (2.83 mmol/L)
History of gestational diabetes mellitus, or delivering a baby > 9 lbs.
Polycystic ovarian syndrome
History of cardiovascular disease
A1C ≥5.7%, impaired glucose tolerance, or impaired fasting glucose on previous testing
Other clinical conditions associated with insulin resistance (e.g., acanthosis nigricans, severe obesity)
In the absence of the above risk factors, screening should begin at 45 years of age.
If results are normal, testing should be repeated at least at three-year intervals, with consideration of more frequent testing depending on risk status and initial results.
United States Preventive Services Task Force (USPSTF) Recommendations
Screen for type 2 diabetes in asymptomatic adults with sustained blood pressure (either treated or untreated) greater than 135/80 mm Hg. Rating: “B” recommendation.
Current evidence is insufficient to assess the balance of benefits and harms of screening for type 2 diabetes in asymptomatic adults with blood pressure of 135/80 mm Hg or lower. Rating: “I” statement.
Diagnostic Criteria for Diabetes Mellitus 3
A random glucose of 200 mg/dL or above, plus symptoms of hyperglycemia like polyuria or unexplained weight loss, or hyperglycemic crisis.
A fasting plasma glucose of greater than or equal to 126 mg/dL.
A hemoglobin A1C greater than or equal to 6.5%.
Oral Glucose Tolerance Test (OGTT) is more sensitive and a little more specific than a fasting glucose, but it is difficult to do and poorly reproducible, so it is not recommended for routine clinical use.
The fasting glucose, OGTT and the A1C need to be confirmed on a different day unless the patient has unequivocal or unquestionable symptoms of hyperglycemia.
Prediabetes
Pre-diabetes affects roughly 57 million people in the U.S. and is defined as the presence of either impaired fasting glucose-IFG (fasting glucose 100-125 mg/dl) or impaired glucose tolerance-IGT (2 hr values of oral glucose tolerance testing 140-199 mg/dl). New evidence shows that damage to end-organs is already occurring during pre-diabetes and that progression to diabetes can be delayed or prevented with lifestyle modification and to a lesser degree with medication.
Diabetic Retinopathy proliferative vs non proliferative 3
Type 1vs 2 referral to opthomalogist
The most frequent cause of new blindness among adults (aged 20-74 years). Laser photocoagulation treatment can slow the progression of retinopathy and reduce vision loss, but it doesn’t restore lost vision. Since the treatment is aimed at preventing vision loss, and retinopathy is asymptomatic for its initial course; it’s important to identify and treat patients early in the course of disease.
In severe, non-proliferative retinopathy, look for the following findings on fundoscopic exam:
Retinal hemorrhages are dark blots with indistinct borders that indicate partial obstruction and infarction.
Cotton wool spots are white spots with fuzzy borders and they indicate areas of previous infarction. They accompany hemorrhages.
Microaneurysms are more punctate dark lesions that indicate vascular dilatation.
Neovascularization is the hallmark of proliferative retinopathy. The growth of new blood vessels is prompted by retinal vessel occlusion and hypoxia.
Type 1 diabetes patients should have their first annual eye exam 5 years after diagnosis. However, type 2 diabetes patients should have their first dilated exam when they are first diagnosed (evidence level B) because roughly 20% of patients will already have some degree of retinopathy at diagnosis.
Recommended Diabetes Follow-Up Laboratory Studies 7
There are four reasons for ordering lab tests at a diabetes follow-up visit: monitoring diabetic control, assessing end organ damage, monitoring side effects of treatment, and uncovering management complications.
Diabetic control is monitored via the Hemoglobin A1C. The A1C is a measurement of glycosylated hemoglobin and represents plasma glucose concentrations over a 4-12 week period of time. Current standards of care recommend initial A1C testing at diagnosis, and follow-up testing at least two times a year in patients who are stable and meeting goal of A1C < 7; perform the A1C quarterly in patients when therapy is changing or they are not meeting goal.
Screening for and monitoring diabetic nephropathy is important for assessing end organ damage. It is recommended at diagnosis and annually according to ADA guidelines. In addition, many diabetes medications are excreted through the kidneys and require annual monitoring to identify renal insufficiency and avoid drug toxicity (e.g. metformin, which can cause metabolic acidosis). 24-hour or timed urine collections are difficult to obtain and add little to the prediction of accuracy of protein and creatinine measurements. The spot urine albumin-to-creatinine ratio is the screening test for microalbuminuria.
Measuring a fingerstick of blood sugar is indicated if a patient acutely endorses symptoms of hyperglycemia or hypoglycemia at the time of the visit. Otherwise, in the setting of diabetes follow-up care, this one measurement does not provide the useful information about glycemic control that can be obtained from an A1C measurement.
The serum creatinine and calculated GFR are used to monitor or stage chronic kidney disease. Automatic calculators are now available that can directly calculate the GFR. Calculated GFR is obtained using the serum creatinine level. The Modification of Diet in Renal Disease (MDRD) Study equation is the recommended method of calculation according to the National Kidney Disease Education Program.
In addition to renal insufficiency, metformin can cause another side effect to take into account when deciding which labs to order. During clinical trials, up to 7% of patients receiving metformin developed asymptomatic subnormal serum vitamin B12 levels. In the setting of neuropathy, too, serum B12 levels would be a very reasonable diagnostic test to order.
According to the ADA, if not performed/available within the past year, ordering screening TSH levelsis indicated in type 1 diabetes, newly diagnosed dyslipidemia, or women over age 50 years as part of the comprehensive diabetes evaluation.
Similarly, a fasting lipid profile is important to obtain as dyslipidemia is very common in diabetes.
ADA/EASD Consensus Algorithm for the Management of Type 2 Diabetes tier 1 and 2
1st Tier (Well-validated studies support this approach)
Step 1: Diagnosis = HbA1C > 6.5% = Lifestyle changes plus Metformin
Step 2: Assessment. (If HbA1C > 8) = Continue lifestyle changes and Metformin + Add either a sulfonylurea (Glyburide, Glipizide (both second generation) or Glimepiride (third generation)) or basal insulin (Insulin Glargine (Lantus) or Insulin Detemir (Levemir) on intermediate-acting insulin (NPH).
Step 3: Reassessment. (If HbA1C > 8) = Continue lifestyle changes and Metformin + add basal insulin or (if already added) intensify insulin regimen. Consider discontinuing sulfonylurea to avoid hypoglycemia.
2nd Tier (LESS well-validated studies support this approach)
Step 4: Explore other treatment options:
Adding rapid acting insulin with meals
Thiazolidinediones: Pioglitazone (Actos), Rosigilitazone (Avandia) - useful for those who cannot tolerate the gastrointestinal side effects of metformin, who have hypoglycemia with sulfonylureas or in addition to these agents. A major concern is that these agents can increase risk of heart failure, edema, and bone fractures.
Meglitinides: Nateglinide (Starlix), Repaglinide (Prandin)
GLP-1 analogs: Exenatide (Byetta), Liraglutide (Victoza) - given via sub Q injection.
DPP-4 Inhibitors: Sitagliptin (Januvia), Saxagliptin (Onglyza), Alogliptin (Nesina)
Amylin analog: Pramlintide (Symlin) - given via sub Q injection
Alpha-glucosidase inhibitors: Acarbose (Precose), Miglitol (Glyset)
Vaccines Recommended for Patients with Diabetes 3
Influenza vaccine should be provided to patients with diabetes annually.
Pneumococcal 23-valent polysaccharide (Pneumovax) should be provided to all patients with diabetes over 2 years of age. A one-time revaccination is recommended for patients over 64 years of age if the vaccine was first received greater than five years ago. Patients should also receive the re-vaccination if they have nephrotic syndrome, chronic renal disease or are immunocompromised. There is also the Pneumococcal 13-valent conjugate (Prevnar), which can be given at least one year after Pneumovax in patients 65 and over. Patients can then receive the additional Pneumovax at least one year after the original Prevnar dose.
Hepatitis B vaccine should be administered to all unvaccinated adults with diabetes, HIV, other immunocompromising conditions, or liver disease.
Diabetes Education: Blood Glucose 2
Optimal range for blood glucose:
fasting blood glucose should be 80 -120 mg/dl
postprandial blood glucose between 1-2 hours after a meal should be < 180 mg/dl
Conditions that contribute to hyperglycemia:
Overeating, missing doses of medication, dehydration, infection and illness, and stress.
