Managing the Ups and Downs of Insulin from Start to Finish in Patients Living with Type 2 Diabetes
Don’t be scared of insulin or hypoglycemia anymore! Our Kashlak Friend of the Pod Dr. Jeff Colburn gives us all the essentials you’ll need in your fanny pack for navigating the ups and downs of insulin in type 2 diabetes.
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Half of the beta cells have lost their function in type 2 diabetes by the time of diagnosis (UK Prospective Diabetes Study 16, 1996). Current guidelines published by the American Diabetes Association (ADA) recommend starting with non-insulin agents such as GLP-1 RA or SGLT2-i, however insulin can be initiated in a patient with HbA1c above 10% to achieve more rapid glycemic control.
Dr. Colburn reflects on patient concerns about insulin initiation– they may have resistance to starting insulin, because they have seen friends or family start insulin and shortly after experience a diabetic complication (such as amputation or dialysis), which they see as cause and effect. It is important to address such misconceptions, and explain that long-accumulating microvascular complications were the cause of the complication, not insulin itself.
Recently published guidelines emphasize the need to steer away from framing insulin as a threat or punishment. Dr. Colburn says that a patient starts insulin not because they failed, but because their beta cells have failed them. Fat deposits in the pancreas decrease beta-cell functionality thereby reaching a threshold where only insulin will be an effective therapy (Inashi and Saisho, 2020).
Per ADA guidelines (ElSayed et al, 2023; Section 9), insulin should be started when a patient with type 2 diabetes has severe hyperglycemia with catabolic symptoms (e.g. glycosuria, ketosis) or when the HbA1c is above 10%. Additionally, insulin could be started when glucose control does not improve with non-insulin treatments, such as metformin, GLP-1 RA or SGLT-2 inhibitors, or if these treatments are cost-prohibitive. It is important to remember that insulin can cause weight gain because it creates a state of over-insulinization from lagging in the subcutaneous tissue. Decreasing the dose of insulin while on other treatments should help mitigate weight gain (and many of these newer agents help with weight loss).
The pancreas produces approximately one unit of basal insulin per hour in an individual without insulin resistance, to match the liver’s sugar output (and more when we eat to cover food intake). To determine how much basal insulin to prescribe, the ADA guidelines recommend starting at a rate of 0.1 or 0.2 units of basal insulin per kilogram per day OR 10 units a day.
Dr. Colburn recommends that patients on insulin check am fasting blood glucose every single day. The fasting glucose goal should be between 90 to 130 mg/dL (ElSayed et al, 2023; Section 6). The ADA recommends increasing a once-daily basal insulin such as glargine by 2 units every three days until the patient meets this fasting glucose goal.
Overbasalization is the titration of the basal insulin dose above what is useful for glucose management (with potential side effects of hypoglycemia and undertreatment of mealtime highs). As the patient approaches 0.5U/kg/day of basal insulin (or per Dr. Colburn, simplify the math and use 50 units a day as the upper threshold of basal insulin), they are at risk of overbasalization and it is time to connect with the patient to discuss mealtime insulin (Cowart 2020; Cowart et al 2023). At this point, mealtime insulin may be needed to address the blood sugar patterns that are not being corrected by basal insulin.
Glargine is one of the most common basal insulin formulations. It has an onset of 2 hours and duration of action of 24 hrs. Determir has a duration of 12 hours and was developed to be used as a twice a day basal insulin. Dr. Colburn reminds us that the same dose should be administered in each injection. Degludec has a 72 hour duration of function and does not peak. This insulin still has to be given every day but as Dr. Colburn mentions, it is more “forgiving” if the next dose is not given at the exact same time. This may be a more useful option for patients that experience low blood sugars while on glargine as can be seen in patients with type 1 diabetes, but less common in type 2 diabetes.
NPH has a bit of a peak effect at 6 hours, and lasts for 12 hours. Because of this peak effect it can cause more hypoglycemia than the other insulins (Semlitsch et al, 2020). Of the longer acting insulins available, our expert refers to NPH as the “hidden tool” because it is inexpensive. . Dr. Colburn recommends that two-thirds of the total dose be dosed in the mornings or when the patient is awake and one-third is dosed twelve hours later. Patients could be started on plain NPH so long as it is dosed twice a day when a once-daily basal insulin is not accessible to the patient.
An alternative to NPH is premixed insulin which contains 70% NPH insulin and 30% regular, fast acting insulin. This insulin is also dosed twice a day and it will peak around 6 hours from when it is given. In Dr. Colburn’s experience, this insulin could be used for patients that need to use a mealtime insulin but are not able to frequently check blood sugars or give themselves frequent injections. The risk of hypoglycemia is also increased with this premixed insulin, thus Dr. Colburn warns us to ensure that patients eat when this peaks to prevent hypoglycemia (Ilag et al 2007). For example, if a patient injects this insulin in the mornings, they must have a meal around lunchtime. Assuming the patient has a larger meal that is slower to digest in the evening, the risk of nighttime hypoglycemia could be mitigated but is still present.
Metformin should be continued when basal insulin is started as recommended in the ADA guidelines. Sulfonylureas trigger insulin release from the beta-cells and should be given at mealtime. As part of his personal practice, Dr. Colburn reduces the sulfonylurea in half when starting basal insulin and continues at this dose unless the patient continues to have hyperglycemia. He suggests checking blood glucose before and after meals until the patient establishes a reliable and stable range of blood glucose without hypoglycemia. These readings should help determine the dosing or discontinuation of sulfonylureas while the patient is using insulin.
Generally speaking, weekly GLP-1 RA injections take about four weeks to reach a steady state and demonstrate their impact on the blood sugars (Hinnen, 2017). Dr. Colburn recommends decreasing the basal insulin by approximately 20% to reduce the chances of hypoglycemia. It should be noted that there are fixed-ratio combination products of basal insulin with GLP-1 RA available on the market that include specific instructions to guide the patient through dosing and titration. Our expert reminds us to counsel patients on the GLP-1 RA side effects including nausea and constipation, which patients can experience even at low doses.
This class of drug can be very effective in patients with blood sugars over 180mg/dL and are less likely to trigger hypoglycemia. Even with this low risk for hypoglycemia, Dr. Colburn’s expert recommendation is to decrease the basal insulin by 10%.
Glucose monitoring is needed when the patient is taking insulin and sulfonylureas but not necessary while the patient is taking metformin, SLGT2-i or GLP-1 RA (ElSayed et al, 2023; Section 7). The fasting morning blood glucose is the most important number to follow because it will inform adjustments made to the basal insulin dose. The recommended fasting blood glucose goal is 90 mg/dL to 130 mg/dL.
Similarly, blood glucose monitoring is needed before administering mealtime insulin, as the reading may affect the amount of meal-time insulin needed. While we didn’t get into the details of correctional insulin in this episode, Dr. Colburn gave an example of lowering the dose of pre-meal insulin if a patient has a blood glucose level at or below 70 mg/dL to prevent hypoglycemia or adding insulin (a correction scale) if the pre-meal blood glucose is quite high.
Dr. Colburn’s practice is to get a sense of the patient’s blood glucose pattern based on their lifestyle and adjust treatment with the following approach.
Deintensify insulin treatment in geriatric patients with multimorbidity and impaired “constitutional health”, to reduce the risk of hypoglycemia (ElSayed et al, 2023; Section 13). Insulin demands drop as patients eat less and lose muscle mass which can happen in anyone but occurs more often with aging (Won Park et al 2006). Additionally, the effect of insulin increases as it lingers longer in patients as kidney function declines. Dr. Colburn’s routine approach for older adults is to decrease insulin by 10% to 20% depending on the degree of hypoglycemia. If compliance with nighttime basal insulin is an issue, the ADA guidelines suggest dosing basal insulin in the mornings. Mealtime bolus doses should be adjusted or even skipped depending on the patient’s diet such as meal frequency or portion sizes (Munshi et al, 2016; Jude et al 2022). Dr. Colburn cautions about the use of GLP-1 RA in geriatric patients; using these agents in severe CKD (GFR <15) is off-label and the side effects could worsen existing conditions such as frailty and weight loss.
Planning for hypoglycemia is a critical part of starting insulin! Encourage patients and their caregivers to be familiar with how to identify and treat hypoglycemia. They should be equipped to identify hypoglycemia symptoms (hunger, anxiety, or sweating), carry a glucose monitoring device (hypoglycemia is blood glucose under 70 mg/dL), and carry a glucose treatment (glucose tabs, gel and glucagon). Once hypoglycemia is identified, it should be treated with 15 grams of glucose such as three or four over-the-counter glucose tablets or glucose gels that can be squeezed into the inside of the patient’s cheek (ElSayed et al, 2023; Section 6). After 15 minutes from dosing with glucose tablets or gel, recheck the patient’s blood sugar to ensure it is no longer in the range of hypoglycemia, otherwise you should repeat the treatment. Emergency services should be contacted if there is no improvement after several attempts.
Dr. Colburn suggests prescribing glucagon injections or intranasal powders to patients who use insulin, and instruct patients to carry this with them. Patients and caregivers should be taught how to administer glucagon since the injection has to be reconstituted. Because glucagon stimulates the liver to release its glycogen reserve, it can only be used once a day and the patient should be advised to resume their normal eating schedule to build up their hepatic glycogen reserve (Boido et al, 2014). The most common side effect after using glucagon is nausea or vomiting so patients should be placed on their side in a recovery position to reduce the risk of aspiration.
Listeners will expertly manage insulin from initiation to titration and de-escalation using updated guidelines from ADA/AACE in patients with diabetes.
After listening to this episode listeners will…
Dr. Jeff Colburn reports no relevant financial disclosures. The Curbsiders report no relevant financial disclosures.
Valdez I, Colburn J, Williams PN, Watto MF. “#397: Insulin, Type 2 Diabetes, Fanny Packs, and Hypoglycemia with Dr. Jeff Colburn”. The Curbsiders Internal Medicine Podcast. thecurbsiders.com/category/curbsiders-podcast May 29, 2023.
Producer, Writer, Show Notes, Infographic and Cover Art: Isabel Valdez, PA-C
Hosts: Matthew Watto MD, FACP; Paul Williams MD, FACP
Reviewer: Leah Witt, MD
Showrunners: Matthew Watto MD, FACP; Paul Williams MD, FACP
Technical Production: PodPaste
Guest: Jeff Colburn, MD
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