What is the workup for a patient with worsening diabetes mellitus (DM) and increasing insulin requirements?

From the Guidelines

The workup for a patient with worsening diabetes mellitus and increasing insulin requirements should prioritize identifying underlying causes of insulin resistance and optimizing insulin therapy, with a focus on simplifying complex insulin regimens and adding noninsulin agents as needed, as recommended by the most recent guidelines 1. The initial step in the workup should include a comprehensive history and physical examination to identify potential causes of worsening glycemic control, such as medication changes, dietary indiscretions, infection, stress, or weight gain. Laboratory testing should include HbA1c to assess long-term glycemic control, fasting and postprandial glucose levels, and a basic metabolic panel to evaluate kidney function.

Key Considerations

• Screen for thyroid dysfunction with TSH and free T4, as hypothyroidism can worsen insulin resistance 1.
• Check for pancreatic insufficiency with pancreatic enzymes if symptoms suggest it.
• Evaluate for Cushing's syndrome with a 24-hour urinary free cortisol or overnight dexamethasone suppression test if clinically suspected.
• Consider screening for latent autoimmune diabetes in adults (LADA) with glutamic acid decarboxylase antibodies in patients initially diagnosed with type 2 diabetes who are rapidly progressing to insulin dependence.
• Review medication adherence and technique for insulin administration, including proper storage and injection sites.

Insulin Therapy Optimization

• For patients on basal and prandial insulins, consider simplifying the regimen by changing the timing of basal insulin from bedtime to morning and titrating the dose based on fasting fingerstick glucose test results 1.
• If mealtime insulin is ≤10 units/dose, discontinue prandial insulin and add a noninsulin agent.
• If prandial insulin is >10 units/dose, decrease the dose by 50% and add a noninsulin agent.
• Add noninsulin agents, such as metformin, if eGFR is ≥45 mg/dL, and consider second-line agents if eGFR is <45 mg/dL or metformin is not tolerated 1.

Additional Recommendations

• Continuous glucose monitoring may help identify patterns of hyperglycemia and inform insulin dose adjustments.
• Consider using carbohydrate counting or the exchange system to estimate nutrient content of meals and adjust insulin doses accordingly 1.
• For planned exercise, reduction in insulin dosage is the preferred method to prevent hypoglycemia, while for unplanned exercise, intake of additional carbohydrate is usually needed 1.

From the FDA Drug Label

The FDA drug label does not answer the question.

From the Research

Workup for Worsening Diabetes Mellitus (DM) and Increasing Insulin Requirements

• The workup for a patient with worsening diabetes mellitus (DM) and increasing insulin requirements involves a systematic approach to evaluate the patient and select the most reasonable therapy 2.
• This approach includes assessing the patient's insulin sensitivity, identifying the underlying cause of the increasing insulin requirements, and adjusting the treatment regimen accordingly 2.
• The use of basal insulin initiation provides an excellent platform to which rapid-acting prandial insulin doses can easily be added, potentially in a stepwise manner, as disease progresses 3.
• Premix insulin regimens are another effective intensification option following basal insulin initiation, but are most effective in insulin-naïve patients 3.

Evaluation of Insulin Requirements

• A number of patients with diabetes require very high (> 2 Ukg⁻¹ day⁻¹), or extremely high (> 3 Ukg⁻¹ day⁻¹), insulin doses for the management of their hyperglycemia 2.
• The evaluation of these patients should include a review of the definitions of insulin sensitivity during normality, the various degrees or categories of insulin resistance, and the expected insulin requirements during each of these states 2.
• A simple alphabetic mnemonic approach can help remember the differential diagnosis, and a clinical algorithm can guide the work-up of these patients 2.

Management Considerations

• The management of patients with worsening diabetes mellitus (DM) and increasing insulin requirements should include the use of basal, prandial, and correction dosing for insulin administration 4.
• For patients on total parenteral nutrition (TPN) with hyperglycemia, regular human insulin can be added to the TPN 4.
• Corticosteroids can cause hyperglycemia and can be managed with neutral protamine hagedorn insulin 4.
• The resumption of the patient's diet and oral medications during transitions of care and before discharge should be carefully managed 4.

Comparison of Insulin Regimens

• Studies have compared the efficacy and safety of different insulin regimens, including biphasic insulin aspart 70/30 and once-daily insulin glargine, in patients with type 2 diabetes mellitus inadequately controlled on basal insulin and oral therapy 5, 6.
• These studies have shown that a 'basal plus' regimen, adding once-daily main-meal fast-acting insulin to basal insulin once daily, can be non-inferior to biphasic insulin twice daily in terms of glycated haemoglobin (HbA1c) concentration 6.