CGM Guided Precise Glycemic Control——A Case of Hypoglycemia Risk Resolution in a Diabetic Patient with End-Stage Renal Disease

Medical History and Basic Information

Chief Complaint:

A 54-year-old female patient was admitted due to "thirst and xerostomia for 15 years and recurrent dizziness and fatigue for 10 days."

Present History:

The patient had a long history of diabetes and had adjusted hypoglycemic regimens multiple times. Two years ago, she started oral administration of "metformin sustained-release tablets 1.0 g bid" and "glipizide tablets 10 mg bid" for hypoglycemia; half a year ago, she repeatedly experienced dizziness and sweating, with multiple finger-stick blood glucose levels below 4 mmol/L, and symptoms relieved after eating. More than 10 days before admission, she successively had multiple episodes of inability to speak and move limbs, accompanied by general fatigue, dizziness, and sweating, with clear consciousness, which improved after eating. Half a day ago, the patient had the above symptoms again. The finger-stick blood glucose measured at the local health center was 1.6 mmol/L, and the symptoms were relieved after glucose-elevating treatment. She was admitted to our department for further glycemic regulation.

Past History:

Type 2 diabetes mellitus(T2DM) with multiple complications (diabetic nephropathy, left eye vitreous hemorrhage, binocular diabetic retinopathy); history of hypertension.

Physical Examination:

Body Mass Index (BMI) 29.8 kg/m²; moderate edema of both lower extremities.

Auxiliary Examinations:

Creatinine 435 μmol/L; fasting blood glucose 7.41 mmol/L; 24-hour urine protein quantification: 5349.15 mg/24h; nerve conduction velocity suggested moderate diabetic peripheral neuropathy.

Diagnosis:

1. T2DM with multiple complications (diabetic nephropathy, diabetic retinopathy, diabetic peripheral neuropathy); 2. Chronic renal failure (uremic phase); 3. Hypertension grade 3 (very high risk); 4. Obesity.

Treatment Regimen Based on Continuous Glucose Monitoring (CGM) Interpretation

The patient had a long course of diabetes and had been taking a combination of biguanides and sulfonylureas for hypoglycemia before admission. She had recently experienced recurrent severe hypoglycemia and was currently in the end-stage of renal disease, with a high risk of recurrent hypoglycemia. After admission, dietary control was recommended first, and no hypoglycemic drugs were administered. Meanwhile, CGM was worn to monitor blood glucose changes to avoid reoccurrence of hypoglycemia. If necessary, reasonable hypoglycemic drugs were selected according to the characteristics of blood glucose changes.

Note: TIR: Time in target blood glucose range (3.9~10.0 mmol/L); TAR: Time above target blood glucose range (>10.0 mmol/L); TBR: Time below target blood glucose range (<3.9 mmol/L)

• Day 2 after admission (April 5): After dietary control, CGM monitoring showed that fasting blood glucose was between 7 mmol/L and 8 mmol/L, which met the control standard, but postprandial blood glucose was between 13 mmol/L and 15 mmol/L, with TIR of 38.8% and TAR of 61.2%. It indicated that blood glucose control had a downward trend but was still at a relatively high level, without hypoglycemia.
• Day 3 after admission (April 6): Analyzing the characteristics of the patient's CGM blood glucose curve, the patient had high postprandial blood glucose during the day and low blood glucose at night. Combined with the patient's renal function and the characteristics of various insulins, insulin detemir 6U subcutaneous injection before breakfast was started for hypoglycemia.
• Days 3-5 after admission (April 6-8): CGM monitoring showed that fasting blood glucose was 7 mmol/L, and postprandial blood glucose was between 10 mmol/L and 11 mmol/L. Postprandial blood glucose was improved compared with before, but the time in target blood glucose range had not yet met the standard.
• Day 6 after admission (April 9): Insulin detemir 8U subcutaneous injection before breakfast was started for hypoglycemia. CGM monitoring showed that fasting blood glucose was 7 mmol/L, postprandial blood glucose was 10 mmol/L, TIR was 91.5%, and TBR was 0%, with stable blood glucose. The above treatment regimen and lifestyle intervention were maintained until discharge, and no hypoglycemia occurred during hospitalization.

Case Summary

The liver is the main source of endogenous net glucose production, and the kidneys also produce and utilize glucose. When liver glycogen content drops below 10 g, gluconeogenesis becomes the only source of glucose production. The latest isotope balance technology has confirmed that the contribution of the kidneys to systemic glucose production in the fasting state is equivalent to that of the liver. During hypoglycemia, renal gluconeogenesis is significantly enhanced (increased by 0.19±0.06 and 0.30±0.07 μmol/kg/min in the liver and kidneys, respectively). Patients with end-stage renal disease (ESRD) have decreased gluconeogenic capacity due to loss of renal function, which is an important reason for the high incidence of hypoglycemia. In addition, patients with ESRD have impaired insulin clearance and poor nutritional status, so blood glucose at night is often difficult to maintain within a reasonable range.

The patient in this case had a long history of diabetes complicated with end-stage renal disease and had experienced multiple episodes of severe hypoglycemia in the past. According to the characteristics of the patient's blood glucose changes monitored by CGM, a reasonable type of insulin was selected. Insulin detemir, which has a relatively short duration of action, was chosen to not only control postprandial hyperglycemia during the day but also reduce the risk of nocturnal hypoglycemia. Blood glucose control was significantly improved, TIR met the standard, and no hypoglycemia occurred (TBR 0%). The application of CGM can monitor the characteristics of patients' blood glucose changes to guide the selection of hypoglycemic drugs, enabling patients to quickly achieve blood glucose targets while reducing the occurrence of hypoglycemia. Moreover, CGM can real-time monitor blood glucose and alert for asymptomatic hypoglycemic events. HbA1c cannot meet the requirements of blood glucose assessment due to the influence of renal anemia, so it is recommended to use the Glucose Management Indicator (GMI) [GMI is an indicator derived from CGM data to estimate the patient's glycated hemoglobin (HbA1c) level] instead of HbA1c. This case highlights the core position of the kidneys in systemic glucose homeostasis and provides a new means for the precise management of diabetic patients with end-stage renal disease, which can delay disease progression, reduce the risk of cardiovascular events, improve patients' quality of life, and increase TIR. Meanwhile, the American Diabetes Association (ADA) Guidelines suggest that for patients with chronic kidney disease (CKD) stages 3-5, since HbA1c may be interfered by various factors, CGM and other tools can be considered preferentially for blood glucose assessment in clinical practice to more accurately reflect the level of blood glucose control (updated in 2023) ^[1].

References:

[1] ElSayed NA, Aleppo G, Aroda VR, et al. Glycemic Targets: Standards of Care in Diabetes—2023. Diabetes Care. 2023;46(Suppl 1):S97–S110. doi:10.2337/dc23-S006