Diabetes Mellitus

Overview

Type I Diabetes Mellitus (T1DM): Caused by autoimmune destruction of beta cells. Always requires insulin. Lean patient with early onset.

Type II Diabetes Mellitus (T2DM): Caused by insulin resistance. Controlled by appropriate diet and exercise and/or oral meds. May require insulin. Chronically overweight/obese patient.

Both T1DM and T2DM have the same long-term complications. Diabetes (especially T2DM) will most frequently be diagnosed on screening. Some T1DM patients may present in Diabetic Ketoacidosis (DKA) while some T2DM patients may present in Hyperosmolar Hyperglycemic State (HHS).

• Symptoms
  • Polyuria (because the patient has glucose in urine)
  • Polydipsia (because the patient is dehydrated)
  • Polyphagia (because the patient is hungry)

Screening for Diabetes Mellitus

Screening for DM can be done with an HbA1C level, fasting plasma glucose, or Oral Glucose Tolerance Test. If fasting plasma glucose is used alone for screening, ≥ 2 abnormal readings are needed to make the diagnosis. The next best step after diagnosing diabetes is to get an A1C level, as this will give an idea of glycemic control over the past 3 months and will be used to dictate therapy.

• No diabetes
  • HbA1C <5.7%
  • Fasting plasma glucose ≤ 5.6 mmol/L
  • Oral Glucose Tolerance Test ≤ 7.8 mmol/L
• Pre-diabetes
  • HbA1C 5.7 – 6.5%
  • Impaired glucose tolerance: Oral Glucose Tolerance Test 7.8 – 11.0 mmol/L
  • Impaired fasting glucose: Fasting plasma glucose 5.6 – 6.9 mmol/L
• Diabetes
  • HbA1C ≥ 6.5%
  • Fasting plasma glucose ≥ 7.0 mmol/L
  • Oral Glucose Tolerance Test ≥ 11.1 mmol/L

Outpatient Management of Diabetes Mellitus

How do we minimize the probability of complications and maximize the patient’s quality of life?

When a new diagnosis of T2DM is made, a determination of how the patient is treated is based primarily on HbA1C levels AND whether or not they have complications. All newly diagnosed diabetics should be screened for complications at the first checkup after diagnosis.

The best initial therapy in a new T2DM patient is metformin (unless contraindicated)

Target HbA1C is ≤ 6.5% (be strict in young patients. May be lax in much older patients due to the risk of hypoglycemia). Follow up HbA1C every 3 months. Manage other comorbidities.

• Treatment if HbA1C ≤ 7.5%
  • Monotherapy (Metformin), in addition to diet and exercise
  • Do not use metformin in liver disease, kidney disease, and respiratory disease (lactic acidosis is a major side-effect)
• Treatment if HbA1C 7.6 – 9%
  • Dual therapy (Metformin + other medication)
• Treatment if HbA1C ≥ 9% without symptoms of complications
  • Insulin therapy
• Treatment if HbA1C ≥ 9% with symptoms of complications
  • Triple therapy (Metformin + 2 other medications)

Screening for Complications

• Macrovascular complications
  • Stroke/TIA
  • Myocardial Infarction
  • Angina
  • Peripheral Vascular disease
  ***due to hyperlipidemia
• Microvascular complications
  • Diabetic retinopathy
  • Nephropathy (albuminuria)
  • Erectile dysfunction
  • Osteomyelitis
  • Infection
• Neuropathic complications
  • Autonomic neuropathy (eg. gastroparesis)
  • Peripheral neuropathy (30-40% of patients. Common complication)

Hypertension

Screening is done as normal (140/90 on two occasions). ACEi (Lisinopril, Captopril) or ARB (Valsartan, losartan) is preferable. Adjunctive therapy with thiazide (hydrocholorthiazide) can be considered. BP goal is <130/80 (140/90 works as well)

Nephropathy

Screening for proteinuria is MANDATORY. ACEis or ARBs slows progression to ESRD

Lipids

Lipids are taken after diagnosis. LDL goal is <130 (3.4). Preferably start a patient with LDL >100 (2.6) on a statin (atorvastatin, lovastatin). Recommend exercise (exercise will lower blood glucose and raise HDL)

Retinopathy

Screening for retinopathy is done at diagnosis and q1y thereafter. Done by ophthalmologists. Symptoms of retinopathy include loss of visual acuity, floaters, and blurred vision. Proliferative retinopathy is the most problematic complication

• Treatment of proliferative retinopathy
  • Surgery (Ophthalmology)
• Treatment of non-proliferative retinopathy
  • Tight glucose control

Infection prophylaxis

Leaves patients in a semi-immunocompromised state leaving them at risk of infection. Annual influenza vaccine AND one-time pneumococcal vaccine

Obesity

Obesity has a causal linkage with T2DM. Weight loss (low carb and low-calorie diet with appropriate exercise) is always recommended with diabetes. Can refer to a bariatric surgeon if BMI > 35.

Smoking cessation

Reduces the risk of macrovascular and microvascular complications, as well as has other obvious health benefits.

Erectile dysfunction

Microvascular complication. May treat with sildenafil, and tadafil (Contraindicated if the patient is on nitrates). Ensure the patient is healthy enough for sex (NYHA class, Rule out unstable angina).

Gastroparesis

Neuropathic complication. Suspect in uncontrolled diabetes, if the patient presents with dyspepsia, nausea, vomiting, or diarrhea. The best test for diagnosis is Barium swallow (gastric emptying time). Treat with metoclopramide OR erythromycin

Peripheral neuropathy

Microvascular complication. Pins and needle sensation, particularly in the feet and legs. Treat with gabapentin, pregabalin OR AEDs (carbamazepine, phenytoin)

Oral Glucose Lowering Agents (OGLAs)

• Drug of choice for a T2DM patient with Congestive heart failure
  • SGLT-2 inhibitor

Metformin

Metformin

The cornerstone of therapy in T2DM along with exercise and diet.

The mechanism is complex (blocks gluconeogenesis, etc.)

• Contraindications
  • Renal disease
  • Advanced cirrhosis
  • Lung diseae
• Adverse effects
  • Lactic acidosis
  • GI upset

SGLT-2 inhibitors

Canaglifozin, Empagliflozin

Fairly new class of drugs. Commonly used as adjuncts to metformin (if failed, dual therapy) OR as an alternative (if Contraindicated).

Blocks glucose reuptake of glucose at the Proximal Convoluted Tubule

• Added benefits of SGLT-2 inhibitors
  • Lowers mortality in HFrEF (systolic HF)
  • Delays progression of renal insufficiency in diabetic nephropathy
• Adverse effects
  • UTI
  • Euglycemic DKA
  • Fournier gangrene

GLP-1 agonists

Exenatide, Liraglutide

Commonly used as an adjunct to metformin or as an alternative. Given as a SC injection (except semaglutide). Very expensive. Has been approved for weight loss (an attractive choice for obese patients). Few but severe adverse effects.

• Contraindications
  • MEN-2 syndrome
  • Personal history or family history of medullary thyroid cancer
• Adverse effects
  • Acute pancreatitis

DPP-4 inhibitors

Sitagliptin, Linagliptin

Commonly used as adjuncts to metformin or as alternatives. It has a similar mechanism to GLP-1 agonists but is weight-neutral. Very few adverse effects (Nausea/vomiting)

Sulfonylureas

Glipizide, Gliburide, Chlorpropamide

Have fallen out of favor (due to weight gain and hypoglycemia). Still may be an appropriate monotherapy for patients in whom metformin is contraindicated.

Increases insulin release.

• Adverse effects
  • Weight gain
  • Hypoglycemia
  • SIADH

Thiazolidinediones

Pioglitazone, Rosiglitazone

Falling out of favor (due to water retention). Still may be an appropriate monotherapy for patients in whom metformin is contraindicated.

Increase peripheral insulin sensitivity. Weight-neutral.

• Contraindications
  • Congestive heart failure
• Adverse effects
  • Liver disturbances
  • Water retention (edema)

Insulin

• Who gets insulin?
  • All T1DM
  • Pt that presents w/DM, A1C ≥ 9.0% AND Sx of complications
  • Pt that fails maximal OGLA therapy
  • In-patient (DKA, HHS)
• Downsides to insulin
  • Injection
  • Compliance
  • Chance of hypoglycemia
  • Must be aware of one’s diet and exercise (involves using a glucometer)
  • Expensive (a whole moral quandary)

Insulin formulations

Rapid-acting insulin: Insulin lispro, Insulin aspart, Insulin glulisine

Short-acting insulin: Regular insulin, 75/25, 70/30, 50/50 (Intermediate (NPH)/Regular preparations)

Intermediate-acting insulin: Insulin NPH (non-proteated Hagedorn)

Long-acting insulin: Insulin detemir, Insulin glargine

• Which insulin is typically given in the morning
  • Long-acting insulin (Glargine, Detemir)
• Which insulin is typically given before meals
  • Short-acting insulin (Lispro)

Once-daily Basal Insulin Regimen

10 U insulin detemir or 10 U insulin glargine in the morning OR at night (usually at night). Prefer to use insulin detemir (Insulin glargine has carcinogenic effects)

Twice-daily Basal Insulin Regimen

70/30 preparation in the morning AND 50/50 preparation in the evening

• Daily dosage: 0.5 U/kg
  • 2/3 of the daily dosage in units is given in the morning (70/30 or 75/25 preparation)
  • 1/3 of the daily dose in units is given in the evening (50/50 preparation)
• Calculate the Twice-daily basal insulin regimen dosage for Mr. Wepukhulu who weighs 112 kg
  • Total units: 56 U (112kg x 0.5 U/kg = 56 U)
  • Morning units: 37 U of 70/30 preparation
  • Evening units: 19 U of 50/50 preparation

Basal-bolus “Prandial” insulin regimen

Twice-daily: Patient takes a long-acting insulin in the morning or at night and rapid-acting insulin before each main meal (breakfast, lunch, dinner) The patient should check blood glucose before injecting themselves with rapid insulin.

• Dosage
  • Long-acting: 10 U insulin glargine OR insulin detemir in the morning or at night
  • Short-acting: 0.1 – 0.3 U/kg of insulin glulisin, insulin lispro, or insulin aspart 15 minutes before meals

Sliding Scale Insulin Regimen

Useful in hospital, particularly because patients have active inflammatory processes or infections which may dramatically alter blood glucose levels. Short-acting insulin is given at scheduled times (q6h, q4h, etc) and dosing is based on the patient’s glucose levels. Would be the ideal insulin regimen but would require a lot of discipline from the patient. Happens automatically in patients with insulin pumps. Know that sliding-scale insulin protocols exist.