Alternating Hypoglycemia and Hyperglycemia in Type 2 Diabetes with Advanced Kidney Disease

Patient Case

TJ is a 75-year-old male with a primary diagnosis of dementia with secondary conditions of chronic kidney disease (CKD) (not on dialysis) and type 2 diabetes (T2DM). He resides at home with his wife and daughter. TJ is prescribed comfort medications only outside of his current diabetic medications which include:

  • Humalog® 100 units/ml; Inject 14 units subcutaneously before meals
  • Lantus® 100 units/ml; Inject 14 units subcutaneously at bedtime

Blood glucose levels via fingerstick and home monitoring have been fluctuating for last 4 days. Mid-day glucose levels range from 300 mg/dl to 400 mg/dl. Three days ago, his glucose was 67 mg/dl at 8am. He was feeling dizzy and hadn’t had breakfast yet – he was given a glass of orange juice and Humalog dose was held. At 10am, glucose was > 200 mg/dl and symptoms resolved.

This morning at 9am, after breakfast, glucose was 391 mg/dl. He received Humalog 14 units before eating and was feeling dizzy with eyes rolling back and shakiness observed. At 11am the hospice nurse arrived in the home. Glucose was 260 mg/dl, so the nurse administered 6 units of Humalog and then checked on him a short time later and found him actively seizing. The seizure resolved quickly. A regimen of “lorazepam 4mg IM every 2 hours as needed” was ordered for active seizures.

TJ’s wife and daughter report that he has no history of seizures (this was his first). He does drink a lot of water and eats 2-3 meals a day with assistance. TJ has good urine output and regular bowel movements. The hospice nurse reports that patient is eating only oatmeal and applesauce, not taking any corticosteroids and prognosis is months.

The nurse and family are seeking guidance on how to manage his fluctuating glucose levels.


CKD is associated with insulin resistance, and in patients with diabetes, glycemic control may deteriorate as kidney function declines. In advanced CKD, however, there is a marked reduction in insulin clearance, leading to a decrease in insulin requirement or even the cessation of insulin therapy in patients with type 2 diabetes. Because of the uncertainty in predicting diabetes medication requirements, an individualized approach is essential for patients with advanced CKD.1


Assess for Gastroparesis and Manage Accordingly

Patients with CKD and diabetes may often have gastroparesis. This complicates the timing of insulin injections (and oral hypoglycemic agents) taken in relation to food intake. Gastric emptying studies can confirm the diagnosis but may not be concordant with hospice goals of care. Look for signs and symptoms of gastroparesis (nausea, vomiting, abdominal pain, early satiety, postprandial fullness, bloating, and, in severe cases, weight loss) and consider a trial of metoclopramide.2,3

Assess for Source of New Seizures and Correct Underlying Cause, Where Feasible

In the absence of an acute insult to the brain, acute symptomatic seizures may be the result of an acute medical illness, metabolic disturbance, substance ingestion or withdrawal:4

  • Hypoglycemia – Hypoglycemic seizures are most common in diabetic patients who take excessive amounts of insulin or oral hypoglycemics.
  • Hyperglycemia – Nonketotic hyperglycemia most commonly occurs in diabetic older adults and can cause focal motor seizures.
  • Hyponatremia – Precipitous falls in serum sodium concentrations can trigger generalized tonic-clonic seizures.
  • Hypocalcemia –May occur after thyroid or parathyroid surgery or in association with renal failure, hypoparathyroidism, or pancreatitis.
  • Hypomagnesemia – Magnesium levels below 0.8 mEq/L may result in irritability, agitation, confusion, myoclonus, tetany, and convulsions, and may be accompanied by hypocalcemia.
  • Uremia – Renal failure and uremia are often associated with seizures, particularly myoclonic seizures
  • Hyperthyroidism – Hyperthyroidism can cause seizures and can exacerbate seizures in patients with epilepsy.
  • Withdrawal states – Substance or medication withdrawal, particularly alcohol and benzodiazepine withdrawal, is associated with seizures.

Prevent Hypoglycemia

Diabetes therapy traditionally focuses on tight glycemic control to lower the long-term risk of developing complications such as retinopathy, kidney disease, and neuropathy.  At the end of life, preventing long-term complications is no longer the goal, and tight glycemic control is not recommended because it places patients at risk of hypoglycemia.

Clinicians should educate patients and caregivers about how disease progression and prognosis affects treatment protocol and help them understand the risks of tight glycemic control. Provide information on the signs and symptoms of both hyper- and hypoglycemia, especially when considering making changes to diabetic medications and glucose testing:

  • Hyperglycemia signs and symptoms: Frequent urination, thirst, hunger, anxiety, confusion, irritability, trouble concentrating, headache, blurry vision, numbness, tingling, recurrent infections, impaired wound healing.5
  • Hypoglycemia signs and symptoms: Headache, confusion, dizziness, personality changes, fatigue, weakness, tiredness, sweating, shakiness, anxiety, elevated heart rate.6

Adjust Insulin Regimen and Monitoring, Eventually Deprescribe

Blood glucose monitoring should be individualized and have a purpose. Testing should not be performed if results will NOT prompt changes in care. If testing is included in the care plan, it should be used to adjust therapy accordingly, not merely to document results.7,8

The Effect of Prognosis on Glycemic Goals 7,9

  • Advanced disease and relatively stable (i.e., Several months to a year life expectancy):
    • No changes at this point; dosing should reflect goal of avoiding hypoglycemia, be less intense and tailored to oral intake
    • Regimen tailored to target fasting glucose ≤ 180 mg/dL.
  • Impending death (i.e., organ failure or limited oral intake) – Several weeks or less life expectancy:
    • Adjust medication regimens to avoid hypoglycemia.
    • Recommend decreasing or stopping insulin and sulfonylurea meds
    • Regimen tailored to target fasting glucose > 180 mg/dL.
  • Actively dying (i.e., multiple organ system failures, end of life symptoms such as agonal respirations) – Life expectancy is usually hours to days:
    • Goal is patient comfort and glycemic control is not a priority.
    • Type I diabetes: Target should be liberal (i.e., <360 mg/dL) and insulin continued only if patient is prone to diabetic ketoacidosis (DKA)
    • Type II diabetes: Discontinue all insulin and non-insulin hypoglycemics


TJ is experiencing alternating hypoglycemia and hyperglycemia due to CKD and potentially sporadic food intake and resulting weight loss. CKD is associated with insulin resistance and uncertainty in predicting diabetes medication requirements. TJ presented with no fever and no signs or symptoms of gastroparesis nor infection – gastroparesis and infection were ruled out as sources of glucose fluctuation. New onset seizures may be the result of hypoglycemia due to basal and prandial insulin doses that were disproportionately adjusted.


  • Continue to have a seizure rescue medication on hand in the home. Lorazepam administered intramuscularly may be sporadically absorbed and intravenous is recommended for managing active seizures. If intravenous administration is not feasible, consider compounded rectal diazepam suppositories as an alternative.
  • Assess TJ’s change in weight and differences in food intake now compared to when the current insulin doses were prescribed.
  • Determine TJ’s daily insulin requirements. Basal insulin (i.e., glargine) impacts nocturnal and fasting glucose levels whereas prandial insulin (i.e., lispro) impacts postprandial glucose excursions.10
    • TJ’s current insulin regimen is disproportionate to dosing standards for basal-bolus regimens -basal insulin should cover 50% of the total daily insulin requirement and the remaining 50% is covered by prandial insulin.11
      • Adjust the nighttime Lantus (glargine) dose to 50% of the daily insulin requirement
      • Adjust Humalog (lispro) total daily dose to 50% of the daily insulin requirement, dividing into thirds to be administered 15 minutes before, or immediately before, each meal.
    • Adjust the glucose goal to match the patient prognosis.

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  2. Palmer BF. Carbohydrate and insulin metabolism in chronic kidney disease. In: UpToDate, Berns JA, et al, eds. Waltham, MA: UpToDate, Inc.; Updated Mar 3, 2023.
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