Ketogenic Diet in a Patient With Type 1 Diabetes Mellitus With Hypoglycemia Unawareness

Introduction: The high fat, low carbohydrate ketogenic diet has become increasingly popular in recent years for weight loss and glycemic control in patients with type 2 diabetes. Although prior studies have suggested this diet can improve glycemic control and decrease glucose variability, the impact of a ketogenic diet on rates of hypoglycemia in patients with hypoglycemia unawareness is not well described. Case Description: Our patient is a 37 year-old woman with Type 1 diabetes for 13 years complicated by hypoglycemia unawareness with HbA1c of 7.7%. Her insulin treatment regimen included insulin glargine 22 units daily, insulin aspart using a 1:15 carbohydrate ratio for prandial insulin dosing with a correction factor of 90. She had 5 episodes of severe hypoglycemia within the previous 3 months. The patient decided to resume a ketogenic diet given her previous improvement in glycemic control. Ketosis was confirmed using urine ketone strips performed by the patient. After 2 weeks on the ketogenic diet, a professional blinded continuous glucose monitor (CGM) was used for 4 weeks to monitor glycemic control. CGM data for weeks 1 and 2 showed overall stability of time in target glucose range [TIR, 60% and 69%, respectively], with a slight increase in time spent below range [TBR, 13% and 17%, respectively]. During week 3, the patient experienced a significant decline in TIR to 31%, and associated increase in hypoglycemia (TBR, 13% to 28%). In addition, glycemic variability increased during this time [CV (coefficient of variation), 40.6% during week 1 to 58.1% during week 3]. Patient did not experience symptoms concerning for DKA, and continued to have asymptomatic hypoglycemia despite reductions in her insulin doses during week 3. Following these dose adjustments, CGM data during week 4 were similar to week 1 (TIR 65%, TBR 10%, CV 35%). Patient stopped following the ketogenic diet after 6 weeks due to social factors. Conclusion: A ketogenic diet was associated with increased frequency of hypoglycemic events. In a patient with Type 1 diabetes and hypoglycemia unawareness, use of ketogenic diet may further increase the risk of severe hypoglycemia.

Characterizing Glycemic Control and Sleep in Adults with Long-Standing Type 1 Diabetes and Hypoglycemia Unawareness Initiating Hybrid Closed Loop Insulin Delivery

Nocturnal hypoglycemia is life threatening for individuals with type 1 diabetes (T1D) due to loss of hypoglycemia symptom recognition (hypoglycemia unawareness) and impaired glucose counter regulation. These individuals also show disturbed sleep, which may result from glycemic dysregulation. Whether use of a hybrid closed loop (HCL) insulin delivery system with integrated continuous glucose monitoring (CGM) designed for improving glycemic control, relates to better sleep across time in this population remains unknown. The purpose of this study was to describe long-term changes in glycemic control and objective sleep after initiating hybrid closed loop (HCL) insulin delivery in adults with type 1 diabetes and hypoglycemia unawareness. To accomplish this, six adults (median age = 58 y ) participated in an 18-month ongoing trial assessing HCL effectiveness. Glycemic control and sleep were measured using continuous glucose monitoring and wrist accelerometers every 3 months. Paired sample t -tests and Cohen’s d effect sizes modeled glycemic and sleep changes and the magnitude of these changes from baseline to 9 months. Reduced hypoglycemia ( d = 0.47 ‐ 0.79 ), reduced basal insulin requirements ( d = 0.48 ), and a smaller glucose coefficient of variation ( d = 0.47 ) occurred with medium-large effect sizes from baseline to 9 months. Hypoglycemia awareness improved from baseline to 6 months with medium-large effect sizes (Clarke score ( d = 0.60 ), lability index ( d = 0.50 ), HYPO score ( d = 1.06 )). Shorter sleep onset latency ( d = 1.53 ; p < 0.01 ), shorter sleep duration ( d = 0.79 ), fewer total activity counts ( d = 1.32 ), shorter average awakening length ( d = 0.46 ), and delays in sleep onset ( d = 1.06 ) and sleep midpoint ( d = 0.72 ) occurred with medium-large effect sizes from baseline to 9 months. HCL led to clinically significant reductions in hypoglycemia and improved hypoglycemia awareness. Sleep showed a delayed onset, reduced awakening length and onset latency, and maintenance of high sleep efficiency after initiating HCL. Our findings add to the limited evidence on the relationships between diabetes therapeutic technologies and sleep health. This trial is registered with ClinicalTrials.gov (NCT03215914).

The Evolution of Hemoglobin A1C Targets for Youth with Type 1 diabetes: Rationale and Supporting Evidence

The American Diabetes Association 2020 Standards of Medical Care in Diabetes (Standards of Care) recommends a hemoglobin A1C of <7% (53 mmol/ml) for many children with type 1 diabetes (T1D), with an emphasis on target personalization. A higher A1C target of <7.5% may be more suitable for youth who cannot articulate symptoms of hypoglycemia or have hypoglycemia unawareness, and for those who do not have access to analog insulins, advanced diabetes technologies, or cannot monitor blood glucoses regularly. Even less stringent A1C targets (e.g. <8%) may be warranted for children with a history of severe hypoglycemia, severe morbidities, or short life expectancy. During the “honeymoon” period and in situations where lower mean glycemia is achievable without excessive hypoglycemia or reduced quality of life, an A1C <6.5% may be safe and effective

The Evolution of Hemoglobin A1C Targets for Youth with Type 1 diabetes: Rationale and Supporting Evidence

The American Diabetes Association 2020 Standards of Medical Care in Diabetes (Standards of Care) recommends a hemoglobin A1C of <7% (53 mmol/ml) for many children with type 1 diabetes (T1D), with an emphasis on target personalization. A higher A1C target of <7.5% may be more suitable for youth who cannot articulate symptoms of hypoglycemia or have hypoglycemia unawareness, and for those who do not have access to analog insulins, advanced diabetes technologies, or cannot monitor blood glucoses regularly. Even less stringent A1C targets (e.g. <8%) may be warranted for children with a history of severe hypoglycemia, severe morbidities, or short life expectancy. During the “honeymoon” period and in situations where lower mean glycemia is achievable without excessive hypoglycemia or reduced quality of life, an A1C <6.5% may be safe and effective

Differential Expression of Inflammatory Markers in Hypoglycemia Unawareness Associated with Type 1 Diabetes: A Case Report

The recurrence of hypoglycemic episodes leads to attenuation of the normal counter-regulatory mechanisms that are controlled by the hypothalamus, which results in hypoglycemia unawareness (HU). In this case report, we described for the first time the differential expression of TNF-α, IL-1β, IL-6, and IFN-γ in a blood sample that was taken from a 27-year-old patient with type 1 diabetes mellitus (T1DM) who was diagnosed with HU. The anti-diabetic regimen is currently based on insulin injection, but the patient is planning to start the use of an insulin pump to have better control of glucose levels. Our results showed a trend toward an increase in the expression of IL-1β, IL-6, and IFN-γ in T1DM patient with HU. However, the mRNA level of TNF-α showed a significant decrease. These observations suggest that systemic inflammation could be an underlying cause of HU.