Late Afternoon Vigorous Exercise Increases Postmeal but Not Overnight Hypoglycemia in Adults with Type 1 Diabetes Managed with Automated Insulin Delivery.

Aim: To compare evening and overnight hypoglycemia risk after late afternoon exercise with a nonexercise control day in adults with type 1 diabetes using automated insulin delivery (AID). Methods: Thirty adults with type 1 diabetes using AID (Minimed 670G) performed in random order 40 min high intensity interval aerobic exercise (HIE), resistance (RE), and moderate intensity aerobic exercise (MIE) exercise each separated by >1 week. The closed-loop set-point was temporarily increased 2 h pre-exercise and a snack eaten if plasma glucose was ≤126 mg/dL pre-exercise. Exercise commenced at ∼16:00. A standardized meal was eaten at ∼20:40. Hypoglycemic events were defined as a continuous glucose monitor (CGM) reading <70 mg/dL for ≥15 min. Four-hour postevening meal and overnight (00:00-06:00) CGM metrics for exercise were compared with the prior nonexercise day. Results: There was no severe hypoglycemia. Between 00:00 and 06:00, the proportion of nights with hypoglycemia did not differ postexercise versus control for HIE (18% vs. 11%; P = 0.688), RE (4% vs. 14%; P = 0.375), and MIE (7% vs. 14%; P = 0.625). Time in range (TIR) (70-180 mg/dL), >75% for all nights, did not differ between exercise conditions and control. Hypoglycemia episodes postmeal after exercise versus control did not differ for HIE (22% vs. 7%; P = 0.219) and MIE (10% vs. 14%; P > 0.999), but were greater post-RE (39% vs. 10%; P = 0.012). Conclusions: Overnight TIR was excellent with AID without increased hypoglycemia postexercise between 00:00 and 06:00 compared with nonexercise days. In contrast, hypoglycemia risk was increased after the first meal post-RE, suggesting the importance of greater vigilance and specific guidelines for meal-time dosing, particularly with vigorous RE. ACTRN12618000905268.

Effects of Dietary Fat and Protein on Glucoregulatory Hormones in Adolescents and Young Adults With Type 1 Diabetes.

CONTEXT: Dietary fat and protein impact postprandial hyperglycemia in people with type 1 diabetes, but the underlying mechanisms are poorly understood. Glucoregulatory hormones are also known to modulate gastric emptying and may contribute to this effect. OBJECTIVE: Investigate the effects of fat and protein on glucagon-like peptide (GLP-1), glucagon-dependent insulinotropic polypeptide (GIP) and glucagon secretion. METHODS: 2 crossover euglycemic insulin clamp clinical trials at 2 Australian pediatric diabetes centers. Participants were 12-21 years (n = 21) with type 1 diabetes for ≥1 year. Participants consumed a low-protein (LP) or high-protein (HP) meal in Study 1, and low-protein/low-fat (LPLF) or high-protein/high-fat (HPHF) meal in Study 2, all containing 30 g of carbohydrate. An insulin clamp was used to maintain postprandial euglycemia and plasma glucoregulatory hormones were measured every 30 minutes for 5 hours. Data from both cohorts (n = 11, 10) were analyzed separately. The main outcome measure was area under the curve of GLP-1, GIP, and glucagon. RESULTS: Meals low in fat and protein had minimal effect on GLP-1, while there was sustained elevation after HP (80.3 ± 16.8 pmol/L) vs LP (56.9 ± 18.6), P = .016, and HPHF (103.0 ± 26.9) vs LPLF (69.5 ± 31.9) meals, P = .002. The prompt rise in GIP after all meals was greater after HP (190.2 ± 35.7 pmol/L) vs LP (152.3 ± 23.3), P = .003, and HPHF (258.6 ± 31.0) vs LPLF (151.7 ± 29.4), P < .001. A rise in glucagon was also seen in response to protein, and HP (292.5 ± 88.1 pg/mL) vs LP (182.8 ± 48.5), P = .010. CONCLUSION: The impact of fat and protein on postprandial glucose excursions may be mediated by the differential secretion of glucoregulatory hormones. Further studies to better understand these mechanisms may lead to improved personalized postprandial glucose management.

The relationship between meal carbohydrate quantity and the insulin to carbohydrate ratio required to maintain glycaemia is non-linear in young people with type 1 diabetes: A randomized crossover trial.

OBJECTIVE: To determine if the relationship between meal carbohydrate quantity and the insulin to carbohydrate ratio (ICR) required to maintain glycaemia is linear in people with type 1 diabetes. METHODS: We used an open labelled randomized four-arm cross-over study design. Participants (N = 31) aged 12-27 years, HbA1c ≤ 64 mmol/mol (8.0%) received insulin doses based on the individual's ICR and the study breakfast carbohydrate quantity and then consumed four breakfasts containing 20, 50, 100 and 150 g of carbohydrate over four consecutive days in randomized order. The breakfast fat and protein percentages were standardized. Postprandial glycaemia was assessed by 5 h continuous glucose monitoring. The primary outcome was percent time in range (TIR) and secondary outcomes included hypoglycaemia, glucose excursion and incremental area under the curve. Statistical analysis included linear mixed modelling and Wilcoxon signed rank tests. RESULTS: The 20 g carbohydrate breakfast had the largest proportion of TIR (0.74 ± 0.29 p < 0.04). Hypoglycaemia was more frequent in the 50 g (n = 13, 42%) and 100 g (n = 15, 50%) breakfasts compared to the 20 g (n = 6, 20%) and 150 g (n = 7, 26%) breakfasts (p < 0.029). The 150 g breakfast glucose excursion pattern was different from the smaller breakfasts with the lowest glucose excursion 0-2 h and the highest excursion from 3.5 to 5 h. CONCLUSIONS: A non-linear relationship between insulin requirement and breakfast carbohydrate content was observed, suggesting that strengthened ICRs are needed for meals with ≤20 and ≥150 g of carbohydrate. Meals with ≥150 g of carbohydrate may benefit from dual wave bolusing.

A Randomized Crossover Trial Comparing Glucose Control During Moderate-Intensity, High-Intensity, and Resistance Exercise With Hybrid Closed-Loop Insulin Delivery While Profiling Potential Additional Signals in Adults With Type 1 Diabetes.

OBJECTIVE: To compare glucose control with hybrid closed-loop (HCL) when challenged by high intensity exercise (HIE), moderate intensity exercise (MIE), and resistance exercise (RE) while profiling counterregulatory hormones, lactate, ketones, and kinetic data in adults with type 1 diabetes. RESEARCH DESIGN AND METHODS: This study was an open-label multisite randomized crossover trial. Adults with type 1 diabetes undertook 40 min of HIE, MIE, and RE in random order while using HCL (Medtronic MiniMed 670G) with a temporary target set 2 h prior to and during exercise and 15 g carbohydrates if pre-exercise glucose was <126 mg/dL to prevent hypoglycemia. Primary outcome was median (interquartile range) continuous glucose monitoring time-in-range (TIR; 70-180 mg/dL) for 14 h post-exercise commencement. Accelerometer data and venous glucose, ketones, lactate, and counterregulatory hormones were measured for 280 min post-exercise commencement. RESULTS: Median TIR was 81% (67, 93%), 91% (80, 94%), and 80% (73, 89%) for 0-14 h post-exercise commencement for HIE, MIE, and RE, respectively (n = 30), with no difference between exercise types (MIE vs. HIE; P = 0.11, MIE vs. RE, P = 0.11; and HIE vs. RE, P = 0.90). Time-below-range was 0% for all exercise bouts. For HIE and RE compared with MIE, there were greater increases, respectively, in noradrenaline (P = 0.01 and P = 0.004), cortisol (P < 0.001 and P = 0.001), lactate (P ≤ 0.001 and P ≤ 0.001), and heart rate (P = 0.007 and P = 0.015). During HIE compared with MIE, there were greater increases in growth hormone (P = 0.024). CONCLUSIONS: Under controlled conditions, HCL provided satisfactory glucose control with no difference between exercise type. Lactate, counterregulatory hormones, and kinetic data differentiate type and intensity of exercise, and their measurement may help inform insulin needs during exercise. However, their potential utility as modulators of insulin dosing will be limited by the pharmacokinetics of subcutaneous insulin delivery.

Additional Insulin Is Required in Both the Early and Late Postprandial Periods for Meals High in Protein and Fat: A Randomized Trial.

CONTEXT: The pattern and quantity of insulin required for high-protein high-fat (HPHF) meals is not well understood. OBJECTIVE: This study aimed to determine the amount and delivery pattern of insulin required to maintain euglycemia for 5 hours after consuming a HPHF meal compared with a low-protein low-fat (LPLF) meal. METHODS: This randomized crossover clinical trial, conducted at 2 Australian pediatric diabetes centers, included 10 patients (12-21 years of age) with type 1 diabetes for ≥ 1 year. Participants were randomized to HPHF meal (60 g protein, 40 g fat) or LPLF meal (5 g protein, 5 g fat) with identical carbohydrate content (30 g). A modified insulin clamp technique was used to determine insulin requirements to maintain postprandial euglycemia for 5 hours. Total mean insulin requirements over 5 hours were measured. RESULTS: The total mean insulin requirements for the HPHF meal were significantly greater than for the LPLF meal (11.0 [CI 9.2, 12.8] units vs 5.7 [CI 3.8, 7.5] units; P = 0.001). Extra intravenous insulin was required for HPHF: 0 to 2 hours (extra 1.2 [CI 0.6, 1.6] units/h), 2 to 4 hours (extra 1.1 [CI 0.6, 1.6] units/h), and 4 to 5 hours (extra 0.6 [CI 0.1, 1.1] units/h) after the meal. There were marked inter-individual differences in the quantity of additional insulin (0.3 to 5 times more for HPHF) and the pattern of insulin delivery (0%-85% of additional insulin required in the first 2 hours). CONCLUSION: The addition of protein and fat to a standardized carbohydrate meal almost doubled the mean insulin requirement, with most participants requiring half of the additional insulin in the first 2 hours.

Both dietary protein and fat increase postprandial glucose excursions in children with type 1 diabetes, and the effect is additive.

OBJECTIVE: To determine the separate and combined effects of high-protein (HP) and high-fat (HF) meals, with the same carbohydrate content, on postprandial glycemia in children using intensive insulin therapy (IIT). RESEARCH DESIGN AND METHODS: Thirty-three subjects aged 8-17 years were given 4 test breakfasts with the same carbohydrate amount but varying protein and fat quantities: low fat (LF)/low protein (LP), LF/HP, HF/LP, and HF/HP. LF and HF meals contained 4 g and 35 g fat. LP and HP meals contained 5 g and 40 g protein. An individually standardized insulin dose was given for each meal. Postprandial glycemia was assessed by 5-h continuous glucose monitoring. RESULTS: Compared with the LF/LP meal, mean glucose excursions were greater from 180 min after the LF/HP meal (2.4 mmol/L [95% CI 1.1-3.7] vs. 0.5 mmol/L [-0.8 to 1.8]; P = 0.02) and from 210 min after the HF/LP meal (1.8 mmol/L [0.3-3.2] vs. -0.5 mmol/L [-1.9 to 0.8]; P = 0.01). The HF/HP meal resulted in higher glucose excursions from 180 min to 300 min (P < 0.04) compared with all other meals. There was a reduction in the risk of hypoglycemia after the HP meals (odds ratio 0.16 [95% CI 0.06-0.41]; P < 0.001). CONCLUSIONS: Meals high in protein or fat increase glucose excursions in youth using IIT from 3 h to 5 h postmeal. Protein and fat have an additive impact on the delayed postprandial glycemic rise. Protein had a protective effect on the development of hypoglycemia.