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Diabetes Mellitus: Management and Therapies (SPECIAL CONSIDERATIONS IN…

- - - - prevention measures
        
        Primary : preventing or delaying onset of type 2 DM in high-risk individuals (obese or with prediabetes) by promoting weight reduction
        
        Secondary: preventing or delaying complications in diabetic individuals by improving glycemic control
        
        Tertiary: managing complications
      - TABLE 418-3
      - goal
        
        in type 1 DM: to coordinate and match caloric intake, both temporally and quantitatively, w/ appropriate amount of insulin.
        Based on patient’s estimate of carb content of a meal, an insulin-to-carbohydrate ratio determines the bolus insulin dose for a meal or snack.
        An important component is to minimize weight gain often associated with intensive diabetes management
        
        in type 2 DM: focus on weight loss + incr prevalence of cardiovascular RFs (HTN, dyslipidemia, obesity) and disease in this population;
        should emphasize modest caloric reduction (low-carb) and increased physical activity
    - - in type 1 or 2: useful for lowering plasma glc (during and following exercise) and incr insulin sensitivity
      - 150 min/week (distributed over at least 3 days) of moderate aerobic physical activity with no gaps longer than 2 days
      - in type 1
        
        depending on preexercise plasma glc, circulating insulin level, and the level of exercise-induced catecholamines, during exercise if
        
        insulin level too low, rise in catecholamines--> incr plasma glc excessively--> ketoacidosis.
        
        insulin level excessive--> reduce hepatic glc production (decreased glycogenolysis, decreased gluconeogenesis) + incr glc entry into muscle--> hypoglycemia.
        
        To avoid exercise-related hyper- or hypoglycemia
        (1) monitor blood glc before, during, and after exercise; (2) delay exercise if blood glc >250 mg/ dL + ketones present; (3) if blood glc <100 mg/dL, ingest carb before exercising; (4) monitor glc during exercise and ingest carb to prevent hypoglycemia; (5) decr insulin doses (based on previous experience) before exercise and inject insulin into a nonexercising area; and (6) learn individual glc responses to different types of exercise and increase food intake for up to 24 h after exercise
      - In type 2 exercise-related hypoglycemia less common but can occur in ppl taking either insulin or insulin secretagogues.
      - Untreated proliferative retinopathy is a relative contraindication to vigorous exercise, because this may lead to vitreous hemorrhage or retinal detachment.
  - - - reflects average glycemic control over the previous 2–3 months. bc RBCs average life span 120 days (glycemic level in preceding month contributes about 50% to HbA1c value).
      - In standardized assays, HbA1c approximates following mean plasma glc values: 6% = 126 mg/dL, 7% = 154 mg/dL, 8% = 183 mg/dL,...
      - In patients achieving glycemic goal: measurement of HbA1c at least twice per year. More frequent testing (every 3 months) warranted when glycemic control inadequate or when therapy changed.
      - Clinical conditions such hemoglobinopathies, anemias, reticulocytosis, transfusions, and uremia may interfere w/ HbA1c result; if one has A1c>15, but blood glc okay-->suspects hemopathies; degree of glycation of other prs, such as albumin, can be used as an alternative indicator of glycemic control when HbA1c is inaccurate; fructosamine assay (measuring glycated albumin) reflects the glycemic status over the prior 2 weeks
  - - - type 1 DM: initial within 5 yrs of diagnosis
      - type 2 DM: initial at time of diagnosis
      - women w/ DM who are pregnant or contemplating pregnancy: initial prior to conception + during first trimester
      - if eye exam normal, repeat examination in 2–3 years
- - - - TABLE 418-5
      - OTHER THERAPIES
        
        Bile acid–binding resins: Bile acid metabolism is abnormal in type 2. colesevelam for treatment of type 2; most common side effects are GI; can incr plasma TGs, should be used cautiously
        
        Bromocriptine : dopamine R agonist
      - FIGURE 418-3
  - - - Short acting: prandial coverage; full biologic activity but less tendency for self-aggregation--> more rapid absorption + onset of action + shorter duration of action--> decr number of hypoglycemic episodes (bc decay of insulin action corresponds to decline in plasma glc after a meal)--> insulin aspart, lispro, or glulisine preferred over regular insulin for prandial coverage
      - Long-acting: provides basal insulin requirements; u. prescribed w/ short-acting insulin; mixing may alter insulin absorption profile (esp short-acting insulins). ex: lispro absorption delayed by mixing w/ NPH--> following guidelines should be followed: (1) mix different insulin formulations in syringe immediately before injection (within 2 min); (2) do not store insulin as a mixture; (3) follow same routine in terms of insulin mixing and administration to standardize the physiologic response to injected insulin; (4) do not mix glargine or detemir w/ other insulins
      - Combinations: Although more convenient for patient (only two injections/day), do not allow independent adjustment of short-acting and long-acting activity
      - TABLE 418-4
    - - shortcoming: injected insulin immediately enters systemic circulation, whereas endo insulin is secreted into portal venous system--> exo insulin administration exposes liver to subphysiologic insulin levels.
      - the most physiologic regimens entail more frequent insulin injections, greater reliance on short-acting insulin, and more frequent capillary plasma glucose measurements.
      - In general, type 1 require 0.5–1 U/kg per day of insulin divided into multiple doses, w/ ~50% of insulin given as basal insulin.
      - preprandial insulin dose determination
        
        meal component: use an insulin-to carbohydrate ratio (a common ratio for type 1:1–1.5 units/10 g of carb, but this must be determined for each individual).
        
        supplemental or correcting component: based on preprandial blood glc (1 unit of insulin for every 50 mg/dL over preprandial glc target OR [body weight in kg] × [blood glucose – desired glucose in mg/dL]/1500).
      - FIGURE 418-1
- - - - Fluid replacement
        
        too rapid a reversal may worsen neurologic function.
        
        After hemodynamic stability achieved: IV fluid administration directed at reversing free water deficit using hypotonic fluids (calculated: averages 9–10 L, should be reversed over next 1–2 days)
        
        K repletion: u. necessary, repeated measurements of serum K (In taking diuretics, deficit can be quite large and may be accompanied by Mg deficiency)
        
        Hypophosphatemia may occur during therapy and can be improved by using KPO4 and beginning nutrition.
      - insulin
        
        IV insulin bolus followed by IV insulin at a constant infusion rate;
        
        As in DKA, glc should be added to IV fluid when plasma glc falls to 250 mg/dL, and insulin infusion rate should be decreased
        
        infusion continued until patient has resumed eating and can be transferred to a SC insulin regimen.
        
        patient should be discharged from hospital on insulin
      - Volume depletion + hyperglycemia prominent features of both HHS and DKA--> therapy shares several elements: careful monitoring of patient’s fluid status, laboratory values, and insulin infusion rate crucial, precipitating problems treated.
        HHS: fluid losses and dehydration u. more pronounced due to longer duration of the illness; patient with HHS u. older, more likely to have mental status changes, and more likely to have a life-threatening precipitating event with accompanying comorbidities.
        HHS has substantially higher mortality rate (up to 15%)
    - - The corrected serum sodium is usually increased (add 1.6 meq to measured sodium for each 5.6-mmol/L [100-mg/dL] rise in the serum glucose).
      - A small anion-gap metabolic acidosis may be present secondary to increased lactic acid. Moderate ketonuria, if present, is secondary to starvation.
    - - Insulin deficiency--> incr hepatic glc production + impairs glc use in skeletal muscle--> Hyperglycemia -->osmotic diuresis--> IV V depletion (exacerbated by inadequate fluid replacement).
      - absence of ketosis in HHS not understood; Presumably, insulin deficiency only relative and less severe than in DKA. Lower levels of counterregulatory hormones and FFAs found in HHS than in DKA; also possible that liver less capable of ketone body synthesis or that insulin/glucagon ratio does not favor ketogenesis.
    - - prototypical px: elderly , type 2, several-week hx of polyuria, weight loss, and diminished oral intake that culminates in mental confusion, lethargy, or coma. (in DKA, symptoms develop over 24 hrs)
      - P/E: profound dehydration + hyperosmolality + hypotension, tachycardia, and altered mental status. Notably absent are symptoms of nausea, vomiting, and abdominal pain and the Kussmaul respirations characteristic of DKA.
      - Precipitated by: a serious, concurrent illness (MI, stroke); Sepsis, pneumonia, and other serious infections frequent; a debilitating condition (prior stroke or dementia) or social situation that compromises water intake usually contributes to development
  - - - decr insulin +
        
        incr glucagon--> shift to glc synth
        
        incr glucagon/catecholamines--> promote glycogenolysis
        
        --> reduces GLUT4-> impairs uptake into skeletal muscle and fat--> reduces IC glc metabolism
        
        incr catecholamines + GH--> incr lipolysis + release of FFAs
        hyperglucagonemia alters hepatic FFA metabolism to favor ketone body formation, through activation of carnitine palmitoyltransferase I; At physiologic pH, ketone bodies exist as ketoacids-->neutralized by HCO3--> HCO3 stores depleted--> metabolic acidosis; Incr lactic acid production also contributes to acidosis.
        The incr FFAs--> incr TG + VLDL production. VLDL clearance also reduced because activity of insulin-sensitive lipoprotein lipase in muscle and fat decr. Hypertriglyceridemia may be severe enough to cause pancreatitis
      - DKA often precipitated by incr insulin requirements, as occurs during a concurrent illness; Complete omission or inadequate administration of insulin by patient or health care team (in a hospitalized patient with type 1 DM) may precipitate DKA; Patients using insulin-infusion devices w/ short-acting insulin may develop DKA, bc even a brief interruption in insulin delivery (e.g., mechanical malfunction) quickly leads to insulin deficiency
    - - characterized by: hyperglycemia, ketosis, metabolic acidosis (incr anion gap), a number of secondary metabolic derangements; Table 418-6
      - Leukocytosis, hyperTG, and hyperlipoproteinemia are commonly found as well
      - Hyperamylasemia: maybe pancreatitis, esp when w/ abdominal pain. However, in DKA amylase is of salivary origin and thus is not diagnostic of pancreatitis. Serum lipase should be obtained if pancreatitis suspected
      - β-hydroxybutyrate synth at a 3x greater rate than acetoacetate; however, acetoacetate is preferentially detected by a commonly used ketosis detection reagent (nitroprusside). Serum ketones present at significant levels (positive at serum dilution of ≥1:8). nitroprusside tablet, or stick, is often used to detect urine ketones; certain medications such as captopril or penicillamine may cause false-positive reactions. Serum or plasma assays for β-hydroxybutyrate preferred bc more accurately reflect true ketone body level.
      - Ketonemia: consistent finding in DKA and distinguishes it from simple hyperglycemia. DDx of DKA includes starvation ketosis, alcoholic ketoacidosis (bicarbonate usually >15 meq/L), and other forms of increased anion-gap acidosis
    - - TABLE 418-8
      - Education: during illness or when oral intake compromised, patients should (1) frequently measure capillary blood glc; (2) measure urinary ketones when serum glc > 300 mg/dL; (3) drink fluids to maintain hydration; (4) continue or increase insulin; and (5) seek medical attention if dehydration, persistent vomiting, or uncontrolled hyperglycemia develop--> early DKA can be prevented or detected and treated appropriately on an outpatient basis
      - appropriate therapy--> mortality rate low (<1%) + related more to underlying or precipitating event
        Venous thrombosis, upper GI bleeding, and ARDS occasionally complicate DKA; major nonmetabolic complication of DKA therapy is cerebral edema, which most often develops in children as DKA is resolving--> overreplacement of free water should be avoided; be khatere hamine monitoring, goft saram dard mikone,....
    - - Diagnosis:
        
        D - Diabetes with sugar > 250
        
        K - Ketosis
        
        A - Acidosis ( pH < 7.2 + Anion Gap Wide)
      - Main Clinical Signs / Symptoms:
        
        D - Diuresis, Delirium / Dizziness, Dehydration
        
        K - Kussmaul Breathing, Ketotic Breath
        
        A - Abd. Pain
      - DKA Precipitators
        
        S - Surgery, Sepsis, Sugar High (Missed insulin), Stress, Substances (Alcohol , Dope)