Type 2 Diabetes Mellitus
According to the Statistics Canada reports, in 2017, 2.3 million people were diagnosed with diabetes. Type 2 diabetes makes 90% of all diabetes. It is estimated that one of ten deaths in Canadian adults were attributable to diabetes in 2008/09. People with diabetes are 3 times at higher risk for cardiovascular diseases, 12 times at risk for hospitalization secondary to renal failure, and 20 times at risk for non-traumatic lower limb amputation. It is also worth to note the association between depression and type 2 diabetes: 30% of people with diabetes have clinically relevant depressive symptoms and individuals with depression have an approximately 60% increased risk of developing type 2 diabetes. Populations at higher risk of type 2 diabetes are the following: South Asian, Asian, African, Hispanic or Aboriginal descent, those who are overweight, older or have low income. Diabetes rates are 3-5 times higher in First Nations.While type 1 DM is predominantly found among adolescent and children due to autoimmune condition where the pancreases completely lose its ability to produce insulin, type 2 DM is found among adults above 40. Type 2 DM is caused by the decrease in production of insulin by pancreas or due to insulin resistance. Obesity, high risk ethnicity, physical inactivity, and smoking are the major causes of insulin resistance. A detailed list of DM risk factors is available in the following link, Table 1: https://guidelines.diabetes.ca/cpg/chapter4
(Government of Canada, 2017; Diabetes Canada 2019)
You are starting to see DM patients in your clinical practicum with some of the basic concepts that you have already learned about DM from your previous RN experience as well as from the NP course curriculum. Now, it is your opportunity to put you abstract learnings into practice.This is where you will actively experiment several steps, used in diagnosing and managing Type 2 DM management.
Screening and Diagnosis of type 2 DM
Order FPG and or A1c Q3yrs for patients above 40yr or for patients at higher risk for DM. Use CANRISK tool to calculate DM risk: http://www.healthycanadians.gc.ca/en/canrisk. More frequent follow- up (6-12 months) is recommended for people with very high risk of DM. A1C is not a reliable test for patients with hemoglobinopathies or anemia.
A1c goalsEvidence indicate that optimal A1c control will help to reduce both microvascular and cardiovascular complications.
- Set A1c goals based on age, comorbidities, life expectancy, and hypoglycemia risk
- Most individuals should aim for an A1c below 7%.
- To reduce CKD and retinopathy risk, aim for A1c below 6.5%, if not at hypoglycemia risk
- Frail elderly, patients with hypoglycemia risk, hypoglycemia unawareness, short life expectance, functionally dependent etc. will aim for an A1c between 7.1 to 8.5%
- Refer patients to a registered dietitian for nutrition counselling
- Encourage physical activity. 150 minutes of moderate to vigorous exercise/ week and resistance exercise 2-3 times/wee. More details can be found on:
- Stress management
- Do regular screening for complication prevention/ arrange q3M DM visits
- Do retinopathy screening at diagnosis and annually.
- Provide cardiovascular protection by initiating statin, ASA, ACEI, SLGT2I// GLP1, as necessary
- Monofilament screening annually to r/o diabetic neuropathy
- ECG: every 3-5 years after 40 years, or earlier, if at higher risk
- BP should be maintained below 130/80mmhg
- LDL- should be below 2mmol/l
- Screen for diabetic nephropathy at the time of diagnosis and annually by testing urine albumin creatine ratio and serum creatinine
- Offer smoking cessation support
Biguanides (Metformin): first line treatment. It reduces hepatic glucose production and improves insulin mediated glucose uptake. No weight gain reported; less hypoglycemia; good evidence on macrovascular protection. Its should be held prior to surgeries and investigations that requires contrast. It should be used with caution in patients with renal failure, hepatic failure, and heart failure. Metformin often started at 500mg OD to TID, with a max of 2500mg, with less benefit over 1500mg; GI side effects are very common.
DPP4Is- Dipeptidyl Peptidase 4 inhibitors. DPP4 is an enzyme that weakens the post prandial incretin effect, contributes to hyperglycemia in type 2 diabetes mellitus (T2DM). DPP4 inhibitors block DPP4 results in GLP-1 mediated glucose-dependent insulin secretion, suppression of glucagon secretion, a delay in gastric emptying, and a decrease in caloric intake likely secondary to centrally mediated signaling. Linagliptin (Trajenta), saxagliptin (Onglyza), and sitagliptin (Januvia) are currently approved for use in Canada. Although this can be administered as monotherapy, it is usually prescribed as a combination therapy with other antihyperglycemic agents.
Glucagon Like Peptide-1 Agonists
GLP-1 is a peptide hormone that increases insulin secretion and decreases glucagon secretion from the pancreas in a glucose-dependent manner. GLP-1 As that are administered as subcutaneous injections, provide pharmacologic levels of GLP-1 that helps to reduces glucose and weight by increasing glucose-dependent insulin secretion and decreasing glucagon secretion, delaying gastric emptying and increasing satiety. The most common adverse effects with the GLP-1 RA class are gastro intestinal reactions and injection site reaction.Contraindicated in pregnancy and for patients with family history medullary thyroid carcinoma or multiple endocrine medullary syndrome. This can be administered with insulin, and or other antihyperglycemic medications. Exenatide (Byetta at 5mg BID to 10mg BID, s/c), or victoza (06mg to 1.8mg daily) are the commonly prescribed GLP-1A in Canada. You may consider this injection for patients who may benefit from significant weight loss to improve insulin resistance.
Sodium Glucose Co-Transporter2 Inhibitors (SGLT2 I).
Canafiglozin (Invokana at 100 to 300mg po OD) is the most recent drug class used in type 2 DM management. This group of medications prevents glucose reabsorption by kidneys leading to increased urinary excretion of glucose. It may precipitate frequent genitourinary infection, hypotension, and hyperkalemia.; used in combination therapy. Prescribe with caution in patients with history of renal failure, osteoporosis.
Insulin Secretagogues, Sulfonylureas.
These agents stimulate both basal and post prandial insulin release. Gliclazide (40-320mg, if MR-30-120mg po OD), glimepiride (1-4mg/ day), glyburide (2.5-20mg /day), and tolbutamide (500mg BID- TID) are the drugs in this classification. Hypoglycemia risk associated with glyburide is very high in elderly. Hypoglycemia, being the common side effects of this class of medication, patients should be educated regarding hypoglycemia, signs and symptoms, prevention, and management.
Insulin secretagogues, Meglitinides
This class of medications promote insulin release; however, due to its shorter duration of action, medication should be taken just prior to meals and skip it if you miss a meal. Medications in this call are the following: nateglinide (Starlix 60-180mg/ day, 0-30 mts before meals), gluconorm (0.5-4mg / day, 0-30 mts before meals)
They influence gene expression in the cell, leading to increased insulin sensitivity. TZD are associated with weight gain, fluid retention, and edema. Evidence also indicate that these agents are associated with increased risk of heart failure, macular edema, and increased risk of fracture. Pioglitazone and Rosiglitazone are the medications listed in this class. Due to their identified long-term risk, prescribe with caution.
Alpha glucosidase inhibitors
Reduces post prandial glucose by inhibiting alpha glucosidase. Acarbose (50-100mg TID with meals) is the agent available in Canada under this classification
To learn more about antihyperglycemic agents and their comparative analysis in terms of reducing A1c, and safety in CKD please refer to the following link: https://guidelines.diabetes.ca/cpg/chapter13 (Figure 1 & Figure 2)
When / how to initiate pharmacotherapy for Type 2 DM management?
Many of us may consider insulin management as a complex, challenging part of diabetes management. However, if you can learn the most common 3 insulin regimes and the type of insulins used in each regime, their action, duration, peak time etc., insulin management can become very interesting. To know about the types of insulin, their peak time, duration etc., follow this link: https://www.healthlinkbc.ca/health-topics/aa122570
There are mainly three common regimes used:
- basal insulin only
- premix insulin
- multiple daily insulin
Basal insulin regime
Basal insulin is the ‘once a day insulin’, often prescribed in conjunction with antihyperglycemic, when a better glycemic control is desired. Let us say, your patient’s A1c is 8.5%, with high FPG, he is almost at the max of all oral medications already (e.g. metformin 500mg TID, Januvia 100mg, Invokana 300mg, gliclazide 60mg). You can add a basal insulin at bed time to achieve a better A1c control. Insulin Detemir (Levemir) and glargine (Lantus) are the basal insulin currently available in Canada. If the patient has metabolic decompensation withA1c 1.5% above target, you can add basal insulin as soon as possible either as a monotherapy or in conjunction with metformin.
- Premix insulin is the combination of a regular acting or rapid acting insulin with intermediate acting insulin.
- Humulin 30/70, Novolin 30/70, 40, 60, 50/50 are the combination of regular acting with NPH insulin.
- Humalog mix 25, Humalog Mix 50, Novomix 30 etc. are the combination of rapid acting insulin with NPH insulin
- The difference between short acting and rapid acting analogues are varied based on there onset, duration, peak time.
If a patient is unable to achieve optimal glycemic control with antihyperglycemic medications, in combination with basal insulin, or experiencing metabolic decompensation, you may switch the patient to premix insulin. Premix insulin is prescribed as a BID dose. The benefit of premix insulin is itsconvenient twice a day regime. The chief disadvantage of this insulin is its risk for hypoglycemia, including nocturnal hypoglycemia. It is also recommended for people who have very regimented lifestyle. The combination of two types of insulins in the same injection and the way they overlap with each other at certain times of the day (mid morning, mid after noon, late evening, and early morning around 2am) make them highly risky for use in patients with frequent hypoglycemia, elderly, people with renal failure, shift workers etc.
Example of a premix regime: Novomix 30 units s/c BID
Multiple daily insulin regime (basal- bolus insulin)
This is a very commonly prescribed insulin regime in which a short acting ora rapid acting insulin is administered with each meal and a basal insulin at bed time. The benefits are: better control on dose adjustment; good for patients who have erratic schedule or eating pattern. The disadvantage is the total number of injections required (4 injections) / day. Insulin Aspart (Novo rapid),Glulisine(Apidra), Lispro (Humalog) are the rapid acting insulin with an onset of action of between 10-15 mts. Available short acting insulin include Humulin R, Novolin ge Toronto that have an onset of action between 30-60 mts.
Example of a Basal- bolus insulin regime:
Novorapid 8 units with meals (TID) and Levemir 10 units hs
To learn more about insulin dose calculation and prescription tools, follow the link: https://guidelines.diabetes.ca/reduce-complications/insulin-prescription-tool
If a woman with type 2 DM is planning pregnancy, she should achieve an A1C below 7% She should be on floc acid 5 mg for the first 3 months pf pregnancy and shall be switched to 1 mg after 3 months, until 6 months post partum. Consider switching to an insulin regime Insulin Aspart and lispro are safer in pregnancy with less hypoglycemia risk
In this stage, you are developing some concrete concepts on diabetes management based on your previous experience, clinical encountersand other associated learning opportunities.
SOAP note (Example)
Visit for DM check up
On basal bolus regime, Lispro 8-8-8, Lantus 12 units
No hypoglycemia symptoms, no hypoglycemia unawareness
attending Diabetes classes
Retinopathy -doing annually
No numbness, tingling, or s/o neuropathy
No chest pain, or sob
Doing 30 mts of aerobic/ day
Checking BP at home, reported as “normal”
CVS- wnl, normal s1s2, no murmurs, no ehs
Monofilament 10/10 – b/ foot
Cr- 88, A1c- 7%
SMBG: FBG-9-10mmol/l, post meal 8-10 mmol/l, Wt:85kg
No s/o metabolic decompensation
Type 2 DM
Increase Lantus insulin to 14 units at hs
Discussed hypoglycemia s/s, management, prevention
Discussed driving safety
Reviewed nutrition, balanced meal, portion control
Continue SMBG, reviewed target, goal set at A1c 7%
f/u with diabetes nurse as directed
DM visit q3 month
In this step, you are reflecting on your learning experience and creating new ideas/ concepts.
Describe your learning experience of managing a patient/s with type 2 DM. Use Kolb’s learning cycle to explain your learning cycle and how you generated new ideas (learning outcome) which will further be actively experimented in your future practice as a NP?
1. Government of Canada (2017). Diabetes in Canada. Retrieved from https://www.canada.ca/en/public-health/services/publications/diseases-conditions/diabetes-canada-highlights-chronic-disease-surveillance-system.html
2.Diabetes Canada (2018). Diabetes guidelines. Retrieved from http://guidelines.diabetes.ca/cpg
3.Vella, A. (2012). Mechanisms of action of DPP4-inhibitors. The Journal of Clinical Endocrinology & Metabolism, 97 (8), 2626–2628,https://doi.org/10.1210/jc.2012-2396
4.Trujillo, J. M., Nuffer, W., & Ellis, S. L. (2015). GLP-1 receptor agonists: a review of head-to-head clinical studies. Therapeutic advances in endocrinology and metabolism, 6(1), 19-28.
5. Rx List (2019). Victoza. Retrieved from https://www.rxlist.com/victoza-drug.htm#medguide
6.Canadian Pharmacist Association (2014). Compendium of therapeutic choices. Ottawa:Author Pecker, M., Crasto, W., (2015). Type 2 Diabetes: Pharmacological management strategies. The pharmaceutical Journal, 295. Retrieved from https://www.pharmaceutical-journal.com/learning/learning-article/type-2-diabetes-pharmacological-management-strategies/20069631.article?firstPass=false
7.Health Link BC (2019). Type of insulin. Retrieved from https://www.healthlinkbc.ca/health-topics/aa122570