Sneak Preview of New Type 1 Diabetes Research to be Presented at EASD Meeting

Mini-dose glucagon is a novel treatment for prevention of exercise-induced hypoglycemia. 
Aerobic exercise tends to lower Blood Glucose (BG) levels in patients with Type 1, and hypoglycemia often results.  Traditional prevention strategies employ decreasing insulin or consuming uncovered carbohydrates.  However, this can still result in hypoglycemia or hyperglycemia. 

This research looked at whether giving mini-dose glucagon subcutaneously prior to exercise might prevent lows, and compared the response of this intervention to traditional strategies.  Fifteen Type 1 adults took part in the study, which was a 4 period crossover trial.  They exercised for 45 minutes without any intervention (control), a 50% basal reduction, took 40 gm of glucose tablets orally, or 150 micrograms of glucagon, with all interventions done five minutes prior to exercise.

With the mini-dose glucagon, there was a slight increase to the average BG levels, as opposed to a BG decrease with the control and with insulin reduction.  The glucose tablets induced a bigger increase in BG.  Six participants developed hypoglycemia during control,  five with insulin reduction, and none with glucose tablets or mini-dose glucagon.  There were five participants who developed hyperglycemia greater than 250 mg/dl with glucose tablets and one with mini-dose glucagon.  The researchers concluded that in order to prevent exercise-induced hypoglycemia, mini-dose glucagon may be more effective than reducing insulin, and mini-dose glucagon may be less likely than carbohydrate ingestion to cause hyperglycemia.

Past research has shown a decrease in body weight and risk of hypoglycemia, and a modest effect on A1c levels, in Type 1 patients who use Multiple Daily Injections (MDI) in conjunction with a GLP-1 receptor agonist such as liraglutide. 
There is not a lot of evidence with regard to how GLP-1 agents work for patients who use insulin pumps.  A six month long randomized, double-blind, placebo-controlled study looked at the safety and efficacy of using liraglutide 1.8 mg in addition to insulin pump therapy in 44 overweight type 1 study participants who had an A1c greater than 7.5% and a Body Mass Index (BMI) over 25.  They were randomized to receive either liraglutide 1.8 mg or placebo daily in addition to their pump therapy. 

Between the two groups, characteristics at baseline were similar for A1c, number of years lived with diabetes, total daily dose of insulin, and weight.  Following six months of treatment, liraglutide decreased A1c and body weight as compared to placebo.  The researchers didn’t note any difference between the groups in terms of total daily insulin dose, time spent in hypoglycemia, heart rate, or blood pressure.  Using the Diabetes Treatment Satisfaction Questionnaire, they learned that satisfaction increased more in the liraglutide group than in the placebo group.  Not surprisingly, gastrointestinal side effects occurred more often with liraglutide than with placebo.  The researchers concluded that in overweight Type 1 patients with insufficient glycemic control, adding liraglutide 1.8 mg daily to insulin pump therapy lowers A1c and body weight, increases satisfaction with treatment–without affecting  total daily insulin dose or time spent in hypoglycemia following six months of treatment.

In Type 1 diabetes, a best practice is to base insulin delivery on carbohydrate counting. 
This research study sought to determine the effect of dose adjustment method on the safety and efficacy of mealtime fast-acting insulin (faster aspart) and insulin Aspart (IAsp) in Type 1 subjects in a six month long study. Participants were randomized to double-blind mealtime (0-2 minutes before the meal) faster aspart or IAsp, both with the basal insulin detemir given once or twice per day.  Participants who were experienced in carb counting continued to use this method, while the remaining subjects used a simple bolus algorithm for their dosing.  They were grouped according to their method of dose adjustment. 

Their findings?  There was a statistically significant bigger A1c reduction in the faster aspart group as compared to the IAsp group, which served to confirm non-inferiority.  Utilizing carb counting, there was a statistically significant A1c reduction for faster aspart vs. IAsp, but it was comparable for both groups using the simple bolus algorithm.  Hypoglycemia rates and bolus insulin dose were comparable between treatments across the adjustment methods.  There weren’t any significant differences in weight gain or in total insulin dose between the treatments regardless of adjustment method.  The bottom line was that faster aspart was effective in providing glycemic control regardless of method of adjustment.  The Type 1 patients who used carb counting to dose saw improved glycemic control with faster aspart vs. IAsp, in conjunction with similar weight gain and insulin dose, and didn’t experience an increase in hypoglycemia risk. 

Sodium glucose cotransporter 2 (SGLT2) inhibitors enhance urinary glucose excretion because they reduce the renal (kidney) threshold for glucose.  This allows glucose to spill into the urine and to exit the body. 
The aim of this study was to look at the effect of the SGLT2 inhibitor empagliflozin (also known as Jardiance)on reabsorption of renal glucose in Type 1 patients, and to contrast the results with those for patients with Type 2.  Seventy five Type 1 participants were given placebo, or empagliflozin 2.5 mg, 10 mg, or 25 mg daily, in addition to their insulin.  The model assumed that the excretion of urinary glucose depended upon blood glucose level and kidney function, and that empagliflozin reduced the renal threshold.   Researchers calculated the renal threshold with placebo to me 181 mg/dl (10.1 mmol/L), and with empagliflozin at steady state, 1 mg and 2.5 mg was 53.4 mg/dl (2.97 mmol/L) and 12.5 mg/dl (0.69 mmol/L)  respectively.  Empagliflozin 10 mg and 25 mg resulted in minimal renal threshold values.   

Researchers concluded that while the parameters were generally similar between the Type 1 and the Type 2 patients, the population simulations showed that the lower renal threshold in Type 1 patients resulted in a higher level of urinary glucose excretion than that which was noted in the Type 2 patients.