Keywords
Ramadan fasting - type 1 diabetes - hypoglycemia - whey protein - continuous glucose
monitoring
Introduction
Fasting during Ramadan is observed by millions of Muslims worldwide, including those
with chronic conditions such as diabetes. Patients with type 1 diabetes mellitus (T1D)
face unique challenges during fasting hours, notably the risk of hypoglycemia, hyperglycemia,
and diabetic ketoacidosis (DKA).[1]
[2]
[3] Despite these risks, many patients choose to fast,[4]
[5] and thus, safe and individualized strategies to support fasting are needed.
Whey protein (WP) has been shown to moderate postprandial glucose excursions by stimulating
insulin secretion, increasing glucagon-like peptide-1 (GLP-1) release, and delaying
gastric emptying.[6]
[7]
[8]
[9] These physiological effects have been observed in both healthy individuals and those
with diabetes. However, most existing studies have been conducted in the context of
type 2 diabetes (T2D) or postprandial glucose control in nonfasting individuals.[6]
[7]
[8]
[9]
[10] Emerging data in individuals with T1D suggest that WP may also reduce the risk of
hypoglycemia in high-vulnerability settings, supporting its potential role in mitigating
hypoglycemia during real-life scenarios, such as postexercise or fasting periods.[11]
[12]
The coingestion of protein with carbohydrate-containing meals improves glycemic profiles
by slowing glucose absorption and promoting insulinotropic and incretin responses.[6]
[7]
[8] This effect may be particularly useful during the predawn meal (Suhoor) in Ramadan, as it helps reduce the risk of early morning hypoglycemia.[13]
[14] This study aims to evaluate whether consuming WP at Suhoor reduces the risk of hypoglycemia among individuals with T1D who fast during Ramadan.
This is the first randomized, crossover trial to evaluate WP supplementation at Suhoor in this population.
Patients and Methods
Study Design and Setting
A randomized, controlled, crossover trial was conducted at the Diabetes Centre of
King Abdulaziz Medical City in Jeddah, Saudi Arabia.
Patients were included if they had been diagnosed with T1D for more than 6 months,
were aged 14 years or older, and were on continuous glucose monitoring (CGM) or multiple
daily injections (MDIs). They were well-informed about fasting requirements and were
willing to comply with the study instructions. Patients with cognitive impairment
or learning disability, renal or hepatic impairment, adrenal insufficiency, pregnancy,
alcohol use, or a diagnosis of psychiatric disease were excluded from the study.
Intervention
Each participant completed two 1-week intervention periods during Ramadan: one with
WP supplementation at Suhoor and one without. Structured dietary education was provided by a dietitian prior to
the intervention. During the supplementation period, participants consumed a WP shake
in addition to their usual Suhoor meal. The shake consisted of one scoop of WP powder (containing 24 g of protein per
scoop) mixed with 200 mL of low-fat milk (∼6 g of protein), providing a total of approximately
30 g of protein per serving. Both the protein supplement and the milk were provided
to participants. The supplement was consumed with the Suhoor meal alongside prandial
insulin. While the WP supplement and milk were standardized, the remaining Suhoor
meal composition was not controlled. Participants maintained a dietary diary throughout
both periods, documenting the components of Suhoor meals, the timing of intake, insulin
dosage, pre- and post-Suhoor blood glucose levels, and the method of WP preparation. Daily food logs, flash CGM
(Freestyle Libre), and pre- and post-Ramadan questionnaires were also used to assess
outcomes. No washout period was included between the two intervention weeks; the risk
of carryover effects was considered minimal given the short half-life of WP.
Outcomes
The primary outcome was the incidence rate of hypoglycemic events and time spent in
hypoglycemia during the study period. The secondary outcomes included the comparison
of other measured variables, including the number of days on which the fast was broken,
parameters of blood glucose control as per the ambulatory glucose profile (AGP) report
(mean blood glucose, mean fasting blood glucose, mean 2-hour postprandial blood glucose,
mean glucose management indicator [GMI], mean glucose variability, mean time in range,
time above range, and time below range), and patient preferences.
Statistical Analysis
Analysis was conducted in accordance with the study objectives. Descriptive statistics
were summarized as mean ± standard deviation (SD) for continuous variables, and as
counts and percentages for categorical variables. Data were analyzed using IBM SPSS
Statistics, version 20.0 (IBM Corp., Armonk, New York, United States). The distribution
of continuous variables was assessed using the Shapiro–Wilk test. Where appropriate,
nonnormally distributed data were log-transformed and reassessed for normality. If
the transformation failed to achieve normality, nonparametric tests were applied.
For inferential analyses, paired-samples t-tests were used to compare pre- and postintervention means for normally distributed
variables. At the same time, Wilcoxon signed-rank tests were applied to nonnormally
distributed data. Statistical significance was defined as a two-sided α of 0.05. Results were presented using appropriate tables and bar graphs. Treatment
effects were expressed as absolute percentage-point differences in time spent within
specified glycemic ranges. Continuous data are reported as mean ± SD unless otherwise
stated.
Results
Demographic and Clinical Characteristics
A total of 41 participants completed the study (53.7% female), with a mean age of
24 ± 4.2 years and an average diabetes duration of 14.1 ± 7.3 years. Most participants
were on MDIs (80.5%), while 19.5% used insulin pumps. 36.6% had well-controlled baseline
glycated hemoglobin levels (< 7%), and 87.8% were in the high-risk category according
to the DaR (Diabetes and Ramadan Alliance) risk score ([Table 1]).
Table 1
Baseline demographic and clinical characteristics, treatments, and lifestyle behaviors
|
Total number of patients
|
41
|
|
Age, y (mean ± SD), range
|
24 ± 4.19 (18–32)
|
|
Sex n (%)
|
|
• Male
|
19 (46.3)
|
|
• Female
|
22 (53.7)
|
|
Duration of diabetes (mean ± SD)
|
14.1 ± 7.30
|
|
Occupation, n (%)
|
|
Student
|
22 (53.7)
|
|
Employee
|
11 (26.8)
|
|
Others
|
8 (19.5)
|
|
Physical activity, n (%)
|
|
• Active
|
13 (31.7)
|
|
• Mildly active
|
18 (43.9)
|
|
Not active
|
10 (24.4)
|
|
Baseline HbA1c (mean ± SD)
|
7.6 ± 1.07
|
|
< 7, n (%)
|
15 (36.6)
|
|
7–9
|
23 (56.1)
|
|
> 9
|
3 (7.3)
|
|
Type of insulin (n)
|
33 MDI, 8 pumps
|
|
Total insulin dose (mean ± SD)
|
|
Basal
|
26.3 ± 11.35
|
|
Prandial
|
32.0 ± 17.35
|
|
Applies carb counting, n (%)
|
18 (43.9)
|
|
History of frequent hypoglycemia
|
|
(≤ 3/week), n (%)
|
20 (66.7)
|
|
(≥ 4/week), n (%)
|
10 (22.7)
|
|
Complications, n (%)
|
|
• No complications
|
36 (87.8)
|
|
• Retinopathy
|
2 (4.9)
|
|
• Nephropathy
|
3 (7.3)
|
|
CGM scan per day (mean ± SD)
|
10 ± 6.59
|
|
DaR risk category, n (%)
|
|
• High
|
36 (87.8)
|
|
• Moderate
|
5 (12.2)
|
Abbreviations: CGM, continuous glucose monitoring; DaR, Diabetes and Ramadan Alliance;
HbA1c, glycated hemoglobin; SD, standard deviation.
Note: Complications and monitoring practices.
Fasting Outcomes
During the 2-week crossover period, 33 participants (80.5%) broke their fast at least
once. The primary reasons for fast-breaking were hypoglycemia (93.9%) and hyperglycemia
(21.2%). The number of participants who broke fast ≥ 1 day was 15 (45.5%) during the
WP week, compared with 18 (54.5%) during the no-WP week (p = 0.623). The mean number of days participants broke their fast was significantly
lower during the WP week (0.94 ± 1.25) compared with the no-WP week (1.15 ± 1.33,
p = 0.008; Wilcoxon signed-rank test). The timing of hypoglycemic events was similar
across groups, with the majority occurring during the morning hours (56.2% WP vs.
57.9% no-WP); however, these differences were not statistically significant (p = 0.837, chi-square test) ([Fig. 1]). No severe hypoglycemia, DKA, or emergency room visits were reported during either
week.
Fig. 1 Comparison of patient-reported timing of breaking fast during whey protein (WP) supplementation
week versus non-WP supplementation week.
CGM Metrics
Hypoglycemic events detected by CGM occurred significantly more frequently during
the post-Suhoor period compared with the pre-Iftar period in both study weeks; however,
there was no significant difference between the two regimens ([Fig. 2]). The mean rate of hypoglycemic events per patient per week did not differ significantly
between the WP and no-WP weeks (0.74 vs. 0.73 events; 95% confidence interval, –0.12
to 0.21; p = 0.885).
Fig. 2 Comparison of mean hypoglycemic events across the day as detected by continuous glucose
monitoring (CGM) during whey protein (WP) supplementation week versus non-WP supplementation.
When analyzed by time of day, the mean number of CGM-detected hypoglycemic events
per patient per week during the WP versus no-WP week was 0.7 versus 1.1 (p = 0.07) for the post-Suhoor period (3–6 a.m.) and 0.3 versus 0.6 (p = 0.05) for the pre-Iftar period (4–6 p.m.) ([Fig. 2]).
No statistically significant differences were observed between the 2 weeks in terms
of average glucose, GMI, glucose variability, or time spent in hypoglycemia ([Table 2], [Fig. 3]). AGP-derived glycemic profiles across the 24 hours were also comparable between
the two regimens ([Fig. 4]).
Table 2
Comparison of AGP report metrics during the WP supplementation week versus the non-WP
supplementation week
|
Characteristics
|
WP
|
No-WP
|
p-Value
|
|
Number
|
41
|
41
|
|
Average glucose (mean ± SD)
|
184.6 ± 35.4
|
179.4 ± 35.3
|
0.23
|
|
GMI (mean ± SD)
|
7.5 ± 1.5
|
7.4 ± 1.5
|
0.74
|
|
Glucose variability (mean ± SD)
|
39.8 ± 8.0%
|
40.8 ± 8.0%
|
0.33
|
|
Average duration of hypos (min) (mean ± SD)
|
91.2 ± 59.5
|
97.2 ± 51.4
|
0.46
|
Abbreviations: AGP, ambulatory glucose profile; GMI, glucose management indicator;
SD, standard deviation; WP, whey protein 24 mg in 200 mL low fat milk.
Fig. 3 Comparison of average hourly blood sugar during whey protein (WP) supplementation
week versus non-WP supplementation week.
Fig. 4 Comparison of ambulatory glucose profile (AGP) report data during whey protein (WP)
supplementation week versus no-WP supplementation. WP: Whey protein 24 mg in 200 mL
low-fat milk. TBR, time below range; level-1: 70 mg/dL, level-2: 50 mg/dL; TIR, time
in range, 70–140 mg/dL; TAR, time above range; level-1: 180 mg/dL, level-2: 250 mg/dL.
Patient Acceptability
The post-Ramadan satisfaction survey revealed that 51.2% of participants found the
protein supplement beneficial, and 68.3% reported that they would be willing to use
it again during Ramadan.
Discussion
Our randomized crossover study shows that consuming WP at Suhoor modestly but significantly reduced the number of fasting days interrupted due to
hypoglycemia (p = 0.008), suggesting a real-world benefit for patients attempting prolonged fasting.
The observed reduction in fast-breaking events is consistent with prior mechanistic
data showing that WP can slow gastric emptying, increase satiety, and blunt postprandial
glucose excursions, mediated in part by enhanced GLP-1 and insulin secretion.[6]
[7]
[8]
[9] These effects are time-dependent and more likely to impact glucose dynamics during
the morning and early afternoon, which aligns with the timing of hypoglycemia observed
in our cohort. Nevertheless, the morning hours (4–11 a.m.) were the most common period
for hypoglycemia in both arms, consistent with patterns observed in previous Ramadan
and fasting-related studies.[13]
[14] This is a physiologically vulnerable period following the predawn meal (Suhoor),
when insulin remains active while nutrient availability declines. Although the distribution
of hypoglycemia timing did not differ significantly between weeks (p = 0.837), the trend toward fewer early episodes in the WP week aligns with the proposed
postprandial stabilizing effects of WP. It is also notable that CGM-detected hypoglycemic
events were reduced near Iftar during the week of the WP, thereby reducing the risk of late-day complications.
In contrast to long-term studies in T2D,[9]
[10] where WP may increase fasting glucose or homeostasis model assessment for insulin
resistance over time, our short-term fasting protocol showed no adverse glycemic effects,
as reflected by stable CGM metrics, including average glucose, GMI, and glucose variability.
Although CGM-detected hypoglycemia events by time of day showed only a nonsignificant
trend toward fewer episodes with WP during the vulnerable periods of post-Suhoor and pre-Iftar, participants experienced significantly fewer fasting interruptions. This difference
may reflect the fact that even small variations in hypoglycemia frequency can influence
the decision to break a fast, while not being large enough to produce statistically
significant changes in CGM-derived outcomes.
Evidence for the use of WP in T1D remains limited but is growing. Conn et al examined
postprandial glycemic responses in youth with T1D on insulin pump therapy. They found
that WP-only meals could be managed with reduced or omitted insulin boluses without
triggering hypoglycemia, suggesting a glycemic-sparing effect of protein under certain
circumstances.[11] Rath et al conducted a randomized crossover trial in adolescents with T1D showing
that ingestion of 50 g WP 3 hours after exercise reduced overnight hypoglycemia, likely
via stimulation of hepatic glucose output through glucagon and incretin pathways.[12] This is the first study to evaluate WP supplementation in T1D during Ramadan using
a randomized controlled design and CGM-based outcomes. The use of WP at Suhoor appears to enhance fasting stability without significant risk of delayed hyperglycemia,
unlike carbohydrate-heavy meals or aggressive basal insulin reductions. The intervention
was well tolerated, and notably, 68.3% of participants expressed willingness to use
WP again, underscoring its feasibility as a safe, practical, and culturally acceptable
adjunct during Ramadan fasting.
Our study has several limitations. First, the modest sample size limited the power
to detect smaller differences in secondary outcomes such as CGM-based glycemic metrics.
However, the randomized crossover design strengthened the analysis by reducing interparticipant
variability and effectively increasing the precision of comparisons. Second, while
the crossover design reduces interparticipant variability, insulin adjustments were
left to participant discretion. This reflects real-world Ramadan practice but may
have introduced variability across intervention periods. Third, although the WP supplement
and milk were standardized, the composition of the remainder of the Suhoor meal was
not controlled and could have influenced the outcomes. Fourth, while CGM data were
complete for all participants, fast-breaking behavior was self-reported and therefore
subject to recall bias. Factors beyond CGM-detected hypoglycemia, such as subjective
symptoms or capillary glucose readings, may have influenced it. Finally, this was
a single-center study conducted in a relatively young Saudi cohort, which may limit
generalizability to other Muslim populations with different dietary practices and
cultural fasting traditions.
Conclusion
WP supplementation at Suhoor significantly reduced the number of fasting days interrupted due to hypoglycemia
in individuals with T1D, without worsening glycemic control or increasing the risk
of adverse events. These findings support WP as a safe and potentially beneficial
dietary adjunct for patients with T1D who wish to fast during Ramadan. Larger trials
are needed to confirm these effects and determine optimal dosing strategies. Moreover,
although this study focused on objective glycemic outcomes, future research could
explore the impact of nutritional strategies such as WP on perceived satiety, confidence
in fasting, and quality of life.
In summary, WP supplementation at Suhoor is a promising strategy to reduce hypoglycemia-related fasting interruptions in individuals
with T1D. Further large-scale, multicenter studies are warranted to confirm its role
in clinical practice.
