Test your medicine knowledge with the MKSAP challenge, in partnership with the American College of Physicians.
A 25-year-old woman with type 1 diabetes mellitus is evaluated for recent-onset glycemic fluctuations without symptomatic hypoglycemia. She was diagnosed with diabetes 7 years ago. Her HbA1c levels since diagnosis have ranged from 6.4% to 7.3%, with the most recent value at 7.3%. She reports eating a carbohydrate-consistent diet at each meal, with little variation in her selection of meals or snacks. She started a new job several months ago but continues her daily exercise routine and sleep schedule. She has no other medical problems or symptoms. Her diabetes treatment regimen is insulin glargine once daily and insulin lispro three times daily.
Physical examination findings and vital signs are normal.
Estimate glomerular filtration rate, serum creatinine level, and urine albumin-creatinine ratio are normal. Her blood glucose values from the previous week are shown below.
Blood glucose values:
| Breakfast (mg/dL [mmol/L]) | Lunch (mg/dL [mmol/L]) | Dinner (mg/dL [mmol/L]) | Bedtime (mg/dL [mmol/L]) |
| 124 (6.9) | 190 (10.5) | 109 (6.1) | 210 (11.6) |
| 110 (6.1) | 92 (5.1) | 112 (6.2) | 126 (7.0) |
| 115 (6.4) | 118 (6.5) | 112 (6.2) | 126 (7.0) |
| 117 (6.5) | 127 (7.0) | 204 (11.3) | 110 (6.1) |
| 108 (6.0) | 101 (5.6) | 122 (6.8) | 114 (6.3) |
| 101 (5.6) | 111 (6.2) | 106 (5.9) | 72 (4.0) |
| 126 (7.0) | 187 (10.4) | 102 (5.7) | 196 (10.9) |
Which of the following is the most likely cause of the fluctuating glycemic control?
A. Antibodies to exogenous insulin
B. Gastroparesis
C. Inadequate insulin doses
D. Inappropriate insulin timing
MKSAP Answer and Critique
The correct answer is D. Inappropriate insulin timing.
The mismatch of timing of insulin administration to food intake with meals, possibly related to the time demands of her new job, is the most likely explanation for the erratic glycemic fluctuations noted on this patient’s blood glucose log. The adequacy of her nocturnal long-acting insulin is reflected in her near-goal pre-breakfast blood glucose levels. However, the major fluctuations occurring around mealtimes are best explained by inconsistent use of her immediate-acting insulin relative to food intake. Meal coverage with insulin should mimic the physiologic pattern seen with endogenous insulin secreted from pancreatic beta cells. Administration of immediate-acting insulins should therefore ideally occur just prior to or at the time of the meal consumption. Because of the rapid onset of action with these agents, shifting the timing of administration away from this physiologic pattern may result in the blood glucose fluctuations seen in this patient. An important aspect of diabetes education is helping patients understand the actions of their prescribed insulin regimen and the importance of timing issues when using them.
Antibodies can develop in response to exposure to exogenous insulin; however, these antibodies are rarely clinically significant and would not adequately explain the blood glucose pattern seen in this patient.
Gastroparesis can cause erratic blood glucose values due to either rapid transit or delayed emptying of food within the digestive system. However, the lack of gastrointestinal symptoms, absence of clinical evidence of other diabetes-related complications, and her hemoglobin A1c history suggesting good diabetic control make gastroparesis a less likely cause of her erratic blood glucose readings.
Inadequate insulin dosing can cause fluctuations in glycemic control. However, this patient reports little variability in her daily diet. She also has several days with evidence of adequate glycemic control on her current insulin regimen doses. Therefore, inadequate dosing is less likely to be the cause of her glycemic variability.
Key Point
- Because meal coverage with insulin should mimic the physiologic pattern seen with endogenous insulin secreted from the pancreatic beta cells as closely as possible, insulin administration in patients with diabetes mellitus should ideally occur prior to or at the time of the meal consumption.
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