Does Reducing Basal Insulin During Ramadan Fasting by Children and Adolescents with Type 1 Diabetes Decrease the Risk of Symptomatic Hypoglycemia?

Abstract

Background:

Ramadan fasting by patients with type 1 diabetes might predispose them to hypoglycemia. There are no data on the optimal way of adjusting basal insulin during fasting. We aim at studying whether reducing basal insulin during Ramadan reduces the frequency of symptomatic hypoglycemia.

Methods:

We enrolled children and adolescents with type 1 diabetes who intended to fast during Ramadan. Logbooks were given to subjects to mark days fasted, symptomatic hypoglycemia, and dose of basal insulin on all days of Ramadan. Logbooks were examined. Glucometers and insulin pumps were downloaded.

Results:

Seventy-five patients were enrolled. The age was 10.2–18.9 (14.5) years. Sixty-eight patients had results analyzed. Forty-one patients were on pumps, and 27 patients were on multiple daily injections (MDI). Mean HbA1c was 7.9 (1.2) and 8.4 (1.3) for the pump and the MDI, respectively (P = 0.007). Thirty-nine patients had hypoglycemia leading to breaking fast. The mean number of episodes of breaking fast was 3 (1–8). Thirty-five of the 68 patients had reduced basal insulin. The difference in the frequency of hypoglycemia in those who reduced/did not reduce insulin was not statistically significant (P > 0.10). Fifteen patients on MDI and 24 patients on pumps had at least one episode of breaking fast. Six and 18 of the patients on MDI and pumps, respectively, reduced basal insulin (P > 0.10).

Conclusion:

This is the first study examining the impact of reduction of basal insulin on hypoglycemia in adolescents. Reducing basal insulin during Ramadan fasting does not decrease the risk of symptomatic hypoglycemia. Use of the insulin pump does not appear to be different from MDI in the frequency of occurrence of hypoglycemia.

Introduction

Ramadan fasting is one of the five pillars of Islam and is obligatory on all healthy adult Muslims. Prepubertal children and patients with chronic illnesses, in whom fasting may be detrimental to health, are exempt from fasting.¹ During the month of Ramadan fasting, no food or drink should be consumed between dawn and sunset. Studies regarding the effect of Ramadan fasting are controversial and not well established in patients with diabetes, particularly with regard to adolescents.

People with type 1 diabetes are considered at a very high risk of developing severe complications,² and some recommendations strongly advise against fasting.³ The Epidemiology of Diabetes and Ramadan (EPIDIAR) study of 1070 patients with type 1 diabetes reported that fasting during Ramadan increased the risk of severe hypoglycemia by 7.5-fold (from 0.4 to 3 events per 100 people per month). During Ramadan, 2% of patients with diabetes had experienced at least one episode of severe hypoglycemia requiring hospitalization.⁴

During fasting of healthy individuals, circulating glucose levels tend to fall, leading to decreased secretion of insulin. In addition, levels of glucagon and catecholamines rise, stimulating the breakdown of glycogen and the stimulation of gluconeogenesis.⁵ In patients with type 1 diabetes, glucagon secretion may fail to increase appropriately in response to hypoglycemia. In addition, patients with type 1 diabetes who have autonomic neuropathy can have defective epinephrine secretion, which is another mechanism to counteract hypoglycemia.⁶

The changes of sleep pattern and food intake during Ramadan are found to be associated with the changes in cortisol level, which might influence the response to fasting in hypoglycemia.⁷

Throughout diabetes units where patients observe Ramadan, various recommendations are suggested to patients in relation to insulin regime and dose adjustment during fasting. In most of the centers, healthcare professionals agree for adolescents to fast if they have good glycemic awareness, reasonable glycemic control and are willing to monitor their blood glucose profile during the fasting.⁸ Various insulin adjustment protocols are practiced; however, there is no solid evidence on the superiority of an individual protocol or guidelines.

Oral hypoglycemic medication adjustment during Ramadan is extensively detailed in the recently launched IDF guidelines.⁹ However, clear evidence-based guidelines on insulin adjustment are lacking. Some studies recommended reducing the total insulin dose to 85% of the pre-fasting dose,¹⁰ and others recommended reducing the total daily dose by 30% with a 30:70 split between long- and short-acting insulins.¹¹ The recently launched IDF guidelines on insulin adjustment in adolescents with type 1 diabetes recommend the reduction of basal insulin by 30%–40% in those on multiple daily injections (MDI). For pump users, the recommendation in these guidelines was to reduce the basal rate of insulin by 20%–40% in the past 3–4 h of fasting.⁹ Similarly, the South Asian Guidelines for Management of Endocrine Disorders in Ramadan recommends reducing basal insulin by 10%–20% during the fasting days.¹² However, these recommendations are not based on data from large study cohorts or randomized, controlled studies. In children and adolescents, very few studies were undertaken to evaluate insulin regime adjustment and, to the best of our knowledge, no control studies were undertaken to evaluate basal insulin adjustment during fasting.

Aim

We aim at studying whether reducing basal insulin during Ramadan fasting reduces the risk of symptomatic hypoglycemia leading to breaking fast in children and adolescents with type 1 diabetes during Ramadan fasting.

Methods

Children and adolescents with type 1 diabetes aged between 10 and 18 years who attended the diabetes clinic at Mafraq Hospital for a follow-up were approached to participate in the study. Patients had their initial visit (visit 1) before Ramadan for enrollment and a second visit within 4 weeks after Ramadan. During visit one, patients were informed about the study, and a consent form was signed by patients older than 15 years or by parents for patients aged between 10 and 15 years. Assent was obtained from the latter group.

Patients were given logbooks and asked to mark the following:

- Days that they fasted.

- Days on which they had broken fast due to symptomatic hypoglycemia.

- Amount of basal insulin taken daily if they were on MDI.

On visit 2, patients were interviewed and their logbooks were studied. Patients on insulin pump therapy had their pumps downloaded. The following information was recorded for all patients:

- Number of days when fasting was broken due to symptomatic hypoglycemia.

- Basal insulin dose used on fasting and nonfasting days (from the logbook in MDI patients and from the pump download in pump patients).

- Number of patients who had hypoglycemia while on reduced or nonreduced basal insulin.

Two groups of children/adolescents were compared. Group 1 (G1) are those who reduced their basal insulin dose during the fasting, and Group 2 (G2) are those who did not do so. For G1, a percentage reduction of insulin dose is calculated. G1 and G2 were subdivided based on the method of treatment, pump or MDI, and development of hypoglycemia. Patients who are on pumps had their pumps downloaded. Basal dose used during Ramadan was compared with the standard basal dose.

Research and ethics approval

Approval to undertake the study was obtained from the Research and Ethics committee at Mafraq Hospital.

Statistical method

Comparison between the groups was done using the Student t-test, and significance of the difference was tested. Binary logistic regression was used for further analysis of dependent and independent variables.

Results

Seventy-five patients were enrolled in the study. Age range (median) was 10.2–18.9 (14.5) years. Sixty-eight patients brought their logbooks on visit 2, and their results were included in the analysis. Forty-two participants (62%) were girls. All had a confirmed diagnosis of type 1 diabetes, with a duration of disease range (mean) of 1–17 (5.7) years. Forty-one patients (60%) were on insulin pump therapy, whereas 27 (40%) subjects were on MDI. All subjects on MDI followed a basal bolus regime of long- and rapid-acting insulin analogs.

On unpaired t-test, mean (SD) HbA1c is 7.9 (1.2) and 8.4 (1.3) for the pump and the MDI groups, respectively. The difference is statistically significant, with a P value of 0.007 (Table 1).

Table 1.

Comparison Between Patients Who Reduced and Did not Reduce Basal Insulin in Terms of Development of Hypoglycemia

	Total number	G1	G2	Significance
All participants	68	35	33
Had hypoglycemia	39	21	18	P > 0.10

G1 denotes the group who reduced their basal insulin, and G2 indicates the group who did not do so.

Out of the 68 patients, 39 had symptomatic hypoglycemia leading to breaking fast. The hypoglycemia episodes occurred within around 6 h before sunset/breaking fast. The mean (range) number of episodes of breaking fast was 3 (1–8). Thirty-five of the 68 patients reduced basal insulin. The reduction of basal insulin in the MDI and the pump group ranged between 10% and 25%. Twenty-four patients reduced their basal insulin by 25%, 8 by 20%, and 3 by 10%. The reduction was more than ∼6 h before breaking the fast. Binary logistic regression was carried out to test the impact of reduction of insulin on the frequency of hypoglycemia, and it showed no statistical significance (P > 0.10) (Table 1).

Fifteen out of 27 patients on MDI broke their fast (56%), whereas 24 out of 41 patients on pumps had at least one episode of breaking fast (59%). In the MDI group, out of the 15 patients who had hypoglycemia, 6 reduced basal insulin. Twenty-four of the pump patients had hypoglycemia. Of those, 18 reduced their basal insulin (Table 2).

Table 2.

Number of Patients Who Developed Hypoglycemia Based on Method of Insulin Delivery and Change of Basal Insulin

	Total number	Pump	MDI	Significance
Method of treatment	68	41	27
HbA1c (SD)		7.9 (1.2)	8.4 (1.3)	P < 0.007
Hypoglycemia	39	24	15
Reduced insulin	35	29	6
Reduced insulin and hypoglycemia	21	18	3	P > 0.10

MDI, multiple daily injections.

Using binary logistic regression with hypoglycemia as the dependent variable and adding the method of insulin delivery to the independent variables in the logistic regression, no statistically significant association was found between the risk of hypoglycemia and the method of insulin delivery (P > 0.10).

Discussion

Hypoglycemia is a major complication in type 1 diabetes. It is estimated to account for 2%–4% of mortality in patients with type 1 diabetes¹³

Ramadan fasting by children is a common practice in Muslim countries. Children with diabetes find fasting boosting their self-esteem and making them feel equal to their peers (unpublished data). Healthcare professionals highlight the risk of fasting and encourage close monitoring of glucose level during fasting.

Protracted hypoglycemia can occur with various forms of basal insulin, which have a duration of action between 18 and 30 h.¹⁴ In a study of a pediatric population by Kaplan et al., symptomatic hypoglycemia was reported and resulted in breaking the fast during 15% of the days. In addition, wide blood glucose fluctuation during fasting and eating hours and episodes of unreported hypoglycemia were clearly noted in the continuous glucose monitoring (CGM) data.¹⁵

Various studies in patients with type 1 diabetes concluded different outcomes. In some studies, Ramadan fasting is proved to be safe if patients comply with frequent glucose monitoring and break their fast should hypoglycemia/hyperglycemia arise.^16

–20 Some young people with type 1 diabetes are aware of the possible risk of fasting; however, they have an intense desire to observe Ramadan and have peer pressure if they do not do so (personal observation). In a recent study by our group, it was reassuring that children and adolescents with diabetes did not object to breaking fast when they encountered symptomatic hypoglycemia (unpublished data).

Some studies showed that fasting glucose levels decrease during Ramadan²¹; however, a recent CGM study showed that glucose level can remain stable during Ramadan.²²

There is some evidence that Ramadan fasting can be safer, in terms of hypoglycemia frequency, in patients on insulin pump therapy.^2,8,23 We did not find a significant difference in the frequency of hypoglycemia between insulin pump users and those on MDI. In fact, there was a slightly higher percentage of pump users having hypoglycemia compared with the MDI group (59% vs. 56%). This difference is not statistically significant (P > 0.1). We postulate that this difference might be attributed to the tighter glycemic control in the pump users who have a lower pre-Ramadan HbA1c (mean of 7.9%) compared with those on MDI whose mean HbA1c is 8.4% (P < 0.007).

The issue of insulin adjustment during Ramadan remained variable in different units. The total daily dose of insulin is recommended to be reduced by many authors.^10,12 Khalil et al. showed that there was a redistribution of insulin over a 24-h period. Basal insulin was decreased during the daytime by 5%–20% from before breaking fast and increased during the nighttime. As no major hypoglycemic episodes were reported, the authors recommended the use of insulin pump therapy during fasting, preferably augmented by the use of CGM.²³

In a study by Khawari et al. on fasting adolescents, a steady fall in blood glucose toward normal by the time of breaking fast is noted. The authors also noticed a greater tendency of hypoglycemia in the basal bolus group. The recommendation from this study was reducing the dose of basal insulin by 10%–20%, which should ensure safer fasting for adolescents.¹⁸ Similar results were shown in patients using insulin pump therapy who fasted safely by adjusting their basal insulin down during the fasting time.² The authors of this study recommended adjusting basal insulin according to blood glucose levels between midday and sunset. In a small case series reported by Hawli et al., patients who monitored blood glucose by four-hourly finger sticks had decreased basal insulin requirements by 5.5% to 25.0% in four patients and did not change in one. There was no reporting of severe hypoglycemia in this series.¹⁷ In our study, we did not find a significant difference in the frequency of hypoglycemia by reducing the basal insulin (P > 0.1). We postulate that if the basal requirement was correctly judged and hence the suitable dose was prescribed before Ramadan, it should not be different during Ramadan when the major changes are related to food intake and timing rather than factors related to basal insulin requirement.

There are some limitations in our study. The findings would be more strongly validated if the study was planned in a prospective design with a group randomized to “reduced basal” and another group with no basal reduction. In addition, getting a subgroup of pump users with a low suspend function will be useful, as switching off by the pump will prevent the symptomatic hypoglycemia and will result in a reduction in potential symptomatic hypoglycemia.

We conclude that reducing basal insulin during Ramadan fasting by children or adolescents with type 1 diabetes does not reduce the risk of hypoglycemia. The use of the insulin pump does not appear to be different from MDI use in terms of frequency of occurrence of hypoglycemia.

Footnotes

Author Disclosure Statement

No competing financial interests exist.

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