Does High-Protein High-Fat Meal Increase Postprandial Glucose Concentrations and Meal-Time Insulin Requirements in Patients With Type 1 Diabetes on Basal-Bolus Insulin Regimen: A Randomized Controlled Trial
Phase: NA
Conditions: Type 1 Diabetes Mellitus
Sponsor: TC Erciyes University

Materials and methods 
Participants 
Thirty patients with T1D who had been treated with basal-bolus insulin regimen were 
recruited at the Mustafa Eraslan and Fevzi Mercan Children’s Hospital, Erciyes University in 
Turkey. There were 14 males and 16 females, with a median age of 16 years (range 16 to 18 
years) and a median duration of diabetes 6.0 years (range 2 to 16 years). Median body mass 
index (BMI) was 20.5±3.01 kg/m2 (range 15.6 to 25.0 kg/m2) and glycated haemoglobin 
(HbA1c) was 7.6 (range 6.0 to 11.2%). The bolus and basal insulin regimen was consisting of 
lispro (n=4) or aspart (n=26) as fast-acting insulin and insulin glargine (n=23) or detemir 
(n=7) as long-acting insulin.  
 
Exclusion criteria included: subjects (i) had any restrictive food intake disorders (eg celiac 
disease or food allergy); (ii) had any diabetes complications (eg neuropathy, nephropathy or 
retinopathy); (iii) diagnosed for <1 year; (iv) were using corticosteroid or any medication that 
could effect gastric emptying; (v) did exercise or had hypoglycemia or ketoacidosis within 24 
hour before the test meals; (vi) had overweight or obese (BMI z score: ≥ 1SD and ≥ 2SD 
respectively); (vii) had not on follicular or peri-ovulatory phases of their menstrual cycles (for 
females). 
 
Study design  
This was a single center, crossover, randomized, controlled study, one standard control meal 
(SM) and three test meals (HPM: high protein meal using carbohydrate counting method, 
HPFM-a: high protein-fat meal using carbohydrate counting method and HPFM-b: high 
protein-fat meal using carbohydrate and fat-protein counting method) were compared on 
postprandial glucose response. During the first visit at the clinic, all patients and their parents 
were instructed about the study. The study was approved by the Ethics Committee on Clinical 
Research Ethics of Erciyes University, Faculty of Medicine (2013/173). A written informed 
consent was obtained from the patients and their parents. 
 
Dietary intervention 
Control and test meals 
On four different occasions each interspersed by 1 week, patients consumed in a random 
order, one standard control meal (SM) and three test meals (HPM, HPFM-a and HPFM-b). 

Each meal was given early in the morning at the same time (08.30 h) and prepared in the 
hospital kitchen. The breakfast meal was chosen as a test meal to eliminate any confounding 
second-meal effect. Controlled conditions were employed throughout the study and the 
factors that adversely affects glycemic response has been minimized: All meals were 
consumed within 20 min; no additional food or drink was allowed in the 4-h postprandial 
period unless required to treat symptomatic hypoglycemia. Activity was limited to sedentary 
activities in the research unit (watching DVD). Fast-acting insulin was injected on the same 
region on arm before the first blood sample collection.   
 
The same amount of carbohydrate (70 g) and fiber (11.5 g) was given to each patient with 
control and test meals. The energy of SM (543 kcal) was calculated as 25% of subjects’ age-
adjusted daily energy requirement. HPM and HPHF meals contained same amount of protein 
(36 g), but differed in fat content (HPM= 17 g, HPHF= 30 g). For SM, HPM, HPFM-a, the 
insulin doses were calculated according to the carbohydrate content of the meals, for HPFM-b 
the insulin dose was calculated according to insulin-to-carbohydrate ratio (ICR) and 
additionally insulin-fat raito. The composition of standard and test meals and total insulin 
administration for each meal were given in Table 1.   
 
Table 1. Composition of test meals 
Parameters 
Unit 
SM 
HMP 
HPFM-a 
HPFM-b 
Energy  
kcal 
535 
591 
702 
702 
Carbohydrate  
g 
70 
70 
70 
70 
 
% 
53 
49 
41 
41 
Protein 
g 
24 
36 
36 
36 
 
% 
18 
25 
21 
21 
Fat  
g 
17 
17 
30 
30 
 
% 
29 
26 
38 
38 
Fiber 
g 
11.5 
11.5 
11.5 
11.5 
Calculated GI 
% 
60.4 
60.4 
60.4 
60.4 
Total insulin administration 
(mean±SD)                           
IU 
7.9±1.6 
 
7.9±1.6 
 
7.9±1.6 
 
11.9±1.6 
 
 
Intervention 
Calculation of insulin dosages 
For CARB counting meals (SM, HPM, HPFM-a) all patients were subjected to intensive 
insulin therapy using insulin–carbohydrate ratio for dosing mealtime boluses. Current ICR 
which was calculated by dividing the total daily insulin dosage into 500 and basal insulin 
dosages were applied to the current individual therapy of the patient and did not chance 

during the control and test meals. Fat and protein was not included in the carbohydrate 
counting algorithms. 
 
For fat protein counting meal (HPFM-b) ICR and additionally insulin–fat ratio were used for 
dosing of mealtime boluses. The fat–protein unit (FPU) is defined as 100 calories of fat and 
protein. HPFM-b meal accounted for 4 FPU (400 kcal from fat and protein). 
 
Assessment of HbA1c anc blood glucose concentrations 
During the first visit at the clinic, fasting blood samples were collected for HbA1c. HbA1c 
concentration assessed using turbidimetric inhibition method (ELISA kit), in accordance with 
the manufacturer’s instructions .Subjects arrived to the hospital in a fasting state (after 8 hours 
night fasting) at 8.00 am and capillary blood glucose values were collected and recorded 
before (0 min) and every 30 minutes thereafter for 240 minutes (30, 60, 90, 120, 150, 210, and 
240 minutes) after control and test meals using glucometer (Accu-Chek; Roche, Mannheim, 
Germany). Subjects with fasting blood glucose (FBG)> 250 mg/dL or 200-250 mg/dL and 
urine ketone (+) were excluded and control and/or test meals were repeated in a different day. 
Test was finalized when hypoglycaemia occurred and repeated in a different day. In case of 
hypoglycaemia (glucose values below 70 mg/dL, 2 episodes) patients were asked to consume 
2 dextrose tablets. No patient had severe hypoglycaemia during the study. 
 
Glycemic response of the meals 
Early (0-120 min), late (120-240 min) and whole (0-240 min) glycemic response of standard 
and test meals were evaluated by area under curve (AUC) calculation.