Diabetes

Suspect DM if:

• Recurrent/difficult to treat fungal infections (also HIV, immune compromise for other reasons)
• Polydipsia, polyuria. Type 1 DM can also have polyphagia because can’t metabolize food properly
• Overt signs of insulin resistance: acanthosis nigricans, elevated BP, obesity

Initial labs for suspected DM

• finger stick blood glucose followed by
• electrolytes,
• BUN,
• creatinine,
• fasting lipids,
• urine microalbumin: creatinine ratio, and
• hemoglobin A1c.

Risks

• At risk for:
  • CV disease,
  • PVD,
  • leading cause of blindness in working age adults,
  • leading cause of ESRD and
  • non-traumatic amputations.
• Also: 
  • peripheral neuropathy,
  • gastroparesis,
  • immune compromise → fungal infections, etc.

Goals for treatment

Try to prevent macrovascular disease (accelerated CAD, accelerated cerebral and peripheral disease) and microvascular disease (retinopathy, neuropathy, nephropathy).

• Glycemic control of HgA1c < 7%
• LDL 70-100
• BP < 130/80
• Lifestyle modifications of diet low in carbs and saturated fat and at least 150 mins/week of exercise at 50-70% max heart rate and resistance activity 3x week.

Type I DM

• AI destruction of pancreatic beta cells → no insulin. Risk factors = viruses, genetics, environmental factors.
• Lack of insulin → fat metabolism. Risk of diabetic ketoacidosis = hyperglycemia, high levels of serum acetone, anion gap metabolic acidosis. Stressors (infection, MI) are risk factors.

Type II DM

• Hyperinsulinemia with peripheral insulin resistance – 90% of cases in the US. Stronger FH than type 1.
• Risk of nonketotic hyperosmolar syndrome – blood glucose can reach 1000. Serum osmolarity > 320 and patient has a large fluid deficit – up to 9L.

Gestational DM

• Increased insulin resistance caused by chorionic somatomammotropin, progesterone, and estrogen – all are insulin antagonists.
• Maternal complications: increased risk of UTIs, preeclampsia, retinopathy, hyperglycemia, DKA
• Fetal complications: congenital malformations, macrosomia, respiratory distress syndrome, hypoglycemia, hyperbilirubinemia, hypocalcemia, polycythemia, hydramnios
• Screen: All women at 24-28 weeks with 1 hour glucose challenge. If > 130, do 3 hour test – hours 0, 1, 2, and 3. Abormal = 2+ outside of range. All screen high risk women at the first visit.

Pregnancy

• Type 2 diabetes – higher risk of fetal malformations because of hyperglycemia during early weeks before gestational diabetes has occurred
• Gestational diabetes → macrosomia and polyhydramnios
• Both gestational and type 2 → shoulder dystocia

Diagnosis

• glucose > 200 with symptoms
• fasting glucose > 126
• 2 hour glucose of > 200 with 75 g
• HgA1C > 6.5. Can do fructosamine in patients with Hgb-opathies, recent blood loss, recent change in diet – measures past 2-3 week

DM Medications

• Rapid-­Acting Insulin
  • – used with meals to decrease the postprandial rise in blood glucose
  • 1) Lispro Insulin (“Humalog”)
  • 2) Insulin Aspart (“NovoLog”)
  • 3) Insulin glulisine (“Apidra”)
• Short-­Acting Insulin
  • – Regular human insulin used with meals to decrease the postprandial rise in blood glucose. Less expensive than rapid-­acting insulin analogues
  • 1) Regular Insulin (“Humalin R”; “Novolin R”)
• Intermediate-­Acting Insulin
  • – used with regular insulin to manage total daily insulin requirements. Usually administered twice daily. Infrequently used.
  • 1) Isophane insulin suspension (NPH) (“Humulin N; Novolin N”)
  • 2) Insulin Zinc Suspension (lente) (“Humulin L”)
• Long-­Acting Insulin
  • – Used as a once-daily long-­acting insulin. Infrequently used.
  • 1) Extended insulin zinc suspension (ultralente) (“Humulin U”)
  • 2) Insulin glargine (analog) (“Lantus”)
  • 3) Insulin determir (“Levemir”)
• Biguanides
  • – decreases glucose output during gluconeogenesis
  • 1) Metformin (“Glucophage”)
    • watch for signs and symptoms of lactic acidosis.
    • Renal excretion.
    • Start at a low dose to avoid GI side effects.
• Sulfonylureas
  • – stimulate insulin secretion
  • – Renal excretion
  • 1) Glimepiride (“Amaryl”)
  • 2) Glipizide (“Glucotrol”)
  • 3) Glyburide (“DiaBeta”, “Micronase”, “Glynase”)
• Thiazolidinediones
  • – improve insulin sensitivity in muscle and adipose tissue, decrease liver gluconeogenesis, increase peripheral glucose utilization. Decrease TGs and increase HDL. Liver metabolism.
  • – hepatic elimination
  • 1) Pioglitazone (Actos)
  • 2) Rosiglitazone (Avandia)
• GLP-1 agonist 
  • Incretin mimetic. Stimulates insulin release. Can add to metformin, sulfonylurea, or TZDs.
  • shown to lower the risk of recurrent cardiovascular events
  • Liraglutide (Victoza)
  • Dulaglutide (Trulicity)
  • Exenatide (Byetta) 
    • very expensive; risk of pancreatitis
• Alpha-glucosidase inhibitors
  • inhibit this enzyme in the small intestine to decrease after meal hyperglycemia
  • Acarbose
• Pramlintide
  • inhibits inappropriately high glucagon during hyperglycemia (e.g., after meals)
• DPP-4 Inhibitors
  • block the inhibitor of incretin hormones, which stimulate insulin release in glucose-dependent manner.
  • Can be used as monotherapy or in combo with other oral agents.
  • Sitagliptin (Januvia)
    • expensive; risk of pancreatitis
  • Saxagliptin (Onglyza)
  • Linagliptin (Tradjenta)
  • Alogliptin (Nesina)

Goals

• HbA1c < 7%, fasting glucose 70-130, 1-2 hour post prandial of < 180.
• BP < 140/90
• LDL < 100.

Hypoglycemia

• Cognitive symptoms = confusion, difficulty concentrating, irritability, hallucinations, focal impairments like hemiplegia
• Sympathetic symptoms → sweating, palpitations, tremulousness, anxiety, hunger
• Causes: fasting, insulin overdose, sulfonylurea abuse, hormonal deficiency – hypoadrenalism, hypopituitary, glucagon
• Treat:
  • Outside of the hospital – IM glucagon, sugar-containing products.
  • At the hospital, 50% dextrose. Watch closely – can recur!
• Daytime Hypoglycemia
  • Mild hypoglycemia during the day
    • reduce sulfonylurea dose by 25%
  • Severe hypoglycemia
    • (requires assistance from someone else) during the day
    • reduce sulfonylurea by 50%
• Nighttime Hypoglycemia
  • For any documented hypoglycemia episode at night
    • reduce insulin dose by 2 units, wait 1 week before any dose increases

Therapy Guidelines for Insulin

• Starting a patient on nighttime basal insulin
  • 1) Before initiating insulin 
    • review behavioral management;
    • teach or review self-monitoring blood glucose monitoring;
    • teach adjustment of insulin dose based on SBGM results;
    • Teach injection technique;
    • Review signs, symptoms, and treatment of hypoglycemia
  • 2) Visit at which insulin is initiated 
    • – calculate initial insulin dose (initial dose = Fasting Plasma Glucose (mg/dL)/18); review patient’s injection technique; review SBGM, adjustment algorithm, and hypoglycemia instructions
  • 3) Subsequent visits
    • – consider a non-­visit review of SBGM (fax, e-­mail, electronic transmission from glucose meter)
• Initiating and adjusting BID Insulin
  • Before starting BID regimen
    • discontinue sulfonylurea; continue Metformin, TZD agent;
    • Review SBGM, new insulin adjustment algorithm, diet and exercise plans;
    • if not already SBGM BID, begin BID monitoring (fasting, before evening meals)
  • Starting Dose 
    • AM: 50% of previous nighttime insulin dose;
    • PM: 50% of previous nighttime insulin dose
  • Dose Adjustment 
    • AM dose adjustments based on before-­‐‑evening-­‐‑meal SBGM readings;
    • PM dose adjustments based on fasting before-­‐‑breakfast SBGM readings
  • Dose adjustment frequency 
    • Make dose reductions based on a reading < 70 mg/dL the very next day;
    • Make dose increases based on the average glucose reading from the previous 3 days every 3 days
  • Dose decrease details 
    • if any before supper plasma glucose measurement is < 70 mg/dL, reduce the before-­breakfast insulin dose by 2 units beginning the next morning;
    • If any fasting plasma glucose measurements is < 70 mg/dL, reduce the before-­supper insulin dose by 2 units beginning that afternoon.

Treatment Strategies for DM

• A1c < 7%
  • Self-management medical nutrition therapy
  • Exercise
• A1c 7-­8%
  • Metformin
• A1c 8-­11%
  • Metformin plus one other drug:
    •  If insulin-deficient -> add sulfonylurea (glipizide)
    •  If insulin defect -> add DPP-­‐‑4 inhibitor (sitagliptin) and GLP-­‐‑1 agonist (exenatide)
    • If insulin-resistant -> add TZD (pioglitazone)
• A1c > 11%
  • Metformin + TZD + basal insulin
  • Add multi-­daily insulin