Available online at
ScienceDirect www.sciencedirect.com Diabetes & Metabolism 41 (2015) 1–4
Editorial
New insights on glucose homoeostasis during Ramadan
Keywords: Glucose homeostasis; Ramadan; Dietary intake
In this issue of Diabetes & Metabolism, Lessan et al. [1] report their experience in patients with diabetes (mostly type 2) who were investigated and compared during Ramadan and non-Ramadan periods. There is cogent evidence that Ramadan fasting disturbs the routine dietary habits of people with diabetes. As mentioned by Lessan et al. [1], the Ramadan fast entails a major shift in the timing and content of meals. It is currently admitted that, in normal conditions such as the absence of any intercurrent disease or illness, the nutrient intakes of people with diabetes should be closely similar to those recommended for the general population of healthy, non-diabetic individuals [2,3]. Weight-maintaining diets are usually prescribed for those who have body weights within the normal range, while calorierestricted diets are generally implemented in those who are overweight or obese [2,3]. In addition, dietary carbohydrates should be distributed throughout the day by spreading nutrient intakes over regular time intervals for the three main meals and, eventually, by additional snacking at mid-morning and/or mid-afternoon times and at bedtime as appropriate. In addition, by combining these dietary recommendations with better due consideration of the glycaemic index of foods [4], it has been demonstrated that it is possible to decrease HbA1c levels at least by 1% (one percentage point), even in those with type 1 diabetes being intensively treated with either insulin pumps or basal–bolus insulin regimens [5]. However, as mentioned above, all recommendations related to the quantity and quality of carbohydrates (the glycaemic load) are usually far from fulfilled during the Ramadan period, which is characterized by both abstinence from eating and drinking from dawn to sunset, and no food or fluid restriction between sunset and dawn [6]. The transition from the fasting to the refeeding period is marked by the consumption of a sunset meal that breaks the fasting state. In the United Arab Emirates, the content of this sunset (iftar) meal has been estimated to provide an average intake of energy and carbohydrates of 1400 kcal and 160 g, respectively [1]. Therefore, using continuous glucose monitoring, it http://dx.doi.org/10.1016/j.diabet.2014.11.005 1262-3636/© 2014 Elsevier Masson SAS. All rights reserved.
is not surprising that a sudden and steep rise in glucose levels was observed by Lessan et al. [1] in all subsets of patients, irrespective of the type of antidiabetic therapies used. 1. Metabolic homoeostasis during Ramadan and consequences for drug treatments After a 12- to 15-h fast, the usual duration of abstinence from eating and drinking during Ramadan, both non-diabetic and diabetic people enter the “real” fasting state after a stepwise transition throughout several metabolic stages [7–9]. The nocturnal eating period is followed by a postprandial state that begins with the last food intake, usually at dawn. During this nocturnal period, any dietary carbohydrates ingested are progressively hydrolysed in the intestines, absorbed as monosaccharides and poured into the systemic circulation for further metabolisation in extrahepatic tissues or stored in the liver as glycogen. Each 4-h postprandial period is followed by a 6-h postabsorptive state, which is metabolically characterized by progressive breakdown (glycogenolysis) of the glycogen stored in the liver during the preceding postprandial period [8,9]. Consequently, all those who have taken their last meal at dawn and not eaten during the daylight hours are in a genuine fasting state at the time of the sunset meal. This latter state is characterized by a progressive shift from glycogenolysis to gluconeogenesis (glucose derived from lactate, alanine and glycerol) and by an increased release of free fatty acids from adipose tissue and, subsequently, an increased production of ketone bodies (Fig. 1) [7]. In insulin-using diabetic patients, especially those with type 1 diabetes, such metabolic changes increase the risk of developing ketoacidosis. This complication does not arise in patients with type 2 diabetes treated with oral antidiabetic drugs (OADs), but it cannot be totally excluded in insulin-requiring patients with type 2 diabetes. Usually, in such patients, abstinence from eating during the daylight hours puts them at risk of either hypoglycaemic episodes or exaggerated hyperglycaemia, depending on whether the dosages of
2
Editorial / Diabetes & Metabolism 41 (2015) 1–4
Fig. 1. Utilization and production of metabolic fuel in normal, healthy people during the postabsorptive state and early starvation [7].
antidiabetic medications (sulphonylureas or insulin) have been insufficiently or excessively reduced [6]. For this reason, sulphonylureas are usually considered unsuitable during Ramadan. As a consequence, short-acting insulin secretagogues (glinides) or glucose-dependent insulinotropic agents [dipeptidyl peptidase (DPP)-4 inhibitors, glucagon-like peptide (GLP)1 receptor agonists] should serve as substitutes for ongoing therapy with long-acting non-glucose-dependent insulin secretagogues such as sulphonylureas [6,10]. In patients treated with insulin, however, it is usually recommended to reduce overall daily dosages and, more specifically, the doses injected at the dawn meal (suhoor) [11]. Furthermore, it is worth noting that the majority of the overall dose should be delivered before the sunset (iftar) meal [11] in patients treated with either twice-daily biphasic insulin regimens or multiple daily insulin injections. In the study by Lessan et al. [1], the overall daily dose of insulin was reduced by 8% during Ramadan. Given the fact that this apparently small reduction was able to maintain satisfactory glycaemic control, it raises the question of whether the usual advice to reduce insulin doses by 20–30%, as reported by Lessan et al. [1] and others [11], is not somewhat exaggerated. 2. A typical case report and its integration into general considerations for Ramadan In September 2008, we, at the outpatients’ clinics of the University Hospital (Montpellier, France), had the opportunity to investigate a subject on an ambulatory basis, using continuous glucose monitoring technology, during Ramadan. The subject’s daily glucose pattern (Fig. 2) was similar to those observed by Lessan et al. [1], including a dietary intake of carbohydrates at the sunset meal that was followed by a rapid and exaggerated increment in glucose levels. Within a time interval of < 2 h, glucose concentrations rose from 130 mg/dL to ≥ 400 mg/dL, and plateaued at an average level of 400 mg/dL overnight until dawn. During the Ramadan period, this patient, who was usually treated (in non-Ramadan periods) with a twice-daily insulin glargine regimen (58 and 20 units before breakfast and dinner, respectively) was instructed to take a single daily dose of insulin
just before the sunset meal, which combined 44 units of insulin glargine and 16 units of short-acting insulin glulisine. Yet, the potency of this high predinner dose of insulin to control blood glucose excursions after the sunset meal was largely annihilated and overcome by a carbohydrate intake that was probably too high a level for the sunset meal, and this high level was further maintained throughout the nocturnal period. At dawn and throughout the subsequent daylight hours, this patient continued to exhibit high circulating concentrations of glucose as a result of the continuous and sustained nocturnal overfeeding. To deal with this situation, the patient took a single dose of insulin (44 units of glargine and 16 units of glulisine) injected at the sunset meal several hours before the beginning of the diurnal period. As illustrated in Fig. 2, the rate of glucose disappearance was relatively constant throughout the period from 08h00 to 20h00, with a progressive glucose decrement from 400 to 130 mg/dL. The long delay required to obtain a near-normal glucose concentration in the late afternoon indicated that a single injection combining prandial and basal insulin analogues at the evening meal on the preceding day was not sufficient to achieve satisfactory 24-h glycaemic control in the face of frank nighttime overeating. Given the latter situation, it might be better to recommend a basal–bolus regimen with injection of an appropriate dose of a rapid insulin analogue before the dawn meal. Another alternative would be to use a twice-daily regimen combining the injection of basal and prandial insulin preparations at both the sunset and early-morning meals, especially when the latter also provides a significant intake of carbohydrates. In fact, according to our observations, it is highly likely that the carbohydrate loads at both the sunset and dawn meals largely exceeded the total body glucose-uptake capabilities (2 mg/kg/min) usually observed during the postabsorptive state in normal healthy people [12]. Bringing together our case report and the observations of Lessan et al. [1], it appears that both the exaggerated glucose excursions after the sunset meal and the sustained overnight hyperglycaemia are the two main glycaemic disorders encountered during Ramadan. However, the findings of Lessan et al. [1] appear to be somewhat reassuring as those investigators found that the impact of such glycaemic
Editorial / Diabetes & Metabolism 41 (2015) 1–4
3
Fig. 2. Continuous glycaemic profile during Ramadan of a patient with type 2 diabetes treated with a combination of long- and short-acting insulin preparations injected once daily before the sunset meal. The patient was also taking metformin and glibenclamide at 3 g/day and 10 mg/day, respectively.
disorders on the overall glycaemic control of patients with type 2 diabetes was rather small. For instance, in their population of diabetes patients considered as a whole, they observed that all parameters used to assess ambient hyperglycaemia (mean glucose value), glucose variability [mean amplitude of glycaemic excursion (MAGE)] and hypoglycaemic risk (proportion of time spent in hypoglycaemia) were not significantly different when non-Ramadan and Ramadan periods were compared [1]. Such results indicate that deterioration of diabetic control during the Ramadan fast can be prevented when structured recommendations are made to patients. In the study by Lessan et al. [1], recommendations were mainly focused on the titration of sulphonylureas and insulin, agents that bring hypoglycaemia risk. On the other hand, dietary advice was given in a somewhat casual manner, as the nutrient composition of the sunset meal was not precisely reported and only estimated from an average assessment based on the usual practice in the United Arab Emirates [1]. 3. Is dietary intake a major problem during Ramadan? While some people may perhaps have a tendency to minimize the role of dietary habits during Ramadan, there still remains the fact that the total amount of carbohydrates in the sunset meal (160 g, with one-third provided as simple sugars) was probably responsible for the exaggerated post-meal glucose surges observed by Lessan et al. Nevertheless, as there are wide intraand interindividual variations and marked differences across population groups in the nutrient contents of the sunset and dawn meals, this is cogent evidence that greater attention should be paid to both meals. First, carbohydrate-containing foods overall should be reduced and, second, foods with the highest content of simple sugars should be given at the end of the sunset meal, as it has been demonstrated that the intestinal absorption of high glycaemic loads is slower when carbohydrates are consumed along with proteins and fats in a mixed meal [13–15].
In particular, attention should also be paid to the glycaemic load (quantity and quality) of carbohydrate-containing foods [16] and the time at which they are given during the sunset meal. However, the glycaemic response to sunset meals containing various carbohydrates of different glycaemic indices has not been documented. Nevertheless, it is well known that Muslims break the fasting state by eating carbohydrate-containing foods that are easy to digest, such as dried dates. This habit usually has no impact on the post-meal glycaemic responses of healthy, non-diabetic individuals. In contrast, exaggerated blood glucose surges can occur in patients with diabetes when an excessive amount of dried dates is consumed at the sunset meal, as the carbohydrate content of this fruit is as high as 70 g per 100 g of edible parts and mostly as simple sugars, including mainly glucose and fructose along with small amounts of sucrose [16]. However, the content of crude fibre in dried dates is relatively high (2.5 g per 100 g), and it is well-known that crude fibre can attenuate glucose absorption. Thus, it is not surprising that, despite differences reported throughout the literature [17], the glycaemic index of dried dates has been estimated at 50% compared with the glucose reference [16]. In addition, at the sunset meal that breaks the fasting state during Ramadan, dried dates are usually consumed with dairy products (milk or thick yoghurt) that contribute by exerting an additional blunting effect on the glucose response. Consequently, the traditional breaking of the fast with dried dates mixed with milk products seems to be appropriate, provided that the amount of dried dates consumed at the sunset meal remains within reasonable limits. In conclusion, it appears that the religious fast at Ramadan results in marked changes in glucose homoeostasis in people with diabetes, especially those treated with insulin. The cornerstone of appropriate management of diabetic patients during this period should be mainly, but not solely, focused on better meal planning [6,10]. Special attention should be paid, first, to the carbohydrate content of the sunset meal in terms of both quantity and quality (glycaemic load) and, second, to eating habits throughout the nocturnal period. In addition, there is a mixed
4
Editorial / Diabetes & Metabolism 41 (2015) 1–4
message in that, while most healthcare professionals attempt to provide appropriate nutritional recommendations for the sunset meal, there is a tendency to be more lax in educating patients about controlling the dawn meal. The present review aims in part to remind people that excessive carbohydrate intakes at the dawn meal can have harmful effects on glycaemic control throughout the day, including an inordinately long delay in the disappearance rate of glucose from plasma. This is especially the case in those who exhibit the “dawn phenomenon”, a spontaneous early-morning rise in blood glucose [18–20]. In diabetics being treated with insulin, any pharmacological treatment should be carefully selected and titrated according to both the patient’s eating patterns and the physician’s own clinical practices. Disclosure of interest The authors declare that they have no conflicts of interest concerning this article. References [1] Lessan N, Hannoun Z, Hasan H, Barakat MT. Glucose excursions and glycaemic control during Ramadan fasting in diabetic patients: insights from continuous glucose monitoring (CGM). Diabetes Metab 2015 [Epub ahead of print]. [2] Franz MJ, Bantle JP, Beebe CA, Brunzell JD, Chiasson J-L, Garg A, et al. Evidence-based nutrition principles and recommendations for the treatment and prevention of diabetes and related complications. Diabetes Care 2002;25:148–98. [3] Evert AB, Boucher JL, Cypress M, Dunbar SA, Franz MJ, Mayer-Davis EJ, et al. Nutrition therapy recommendations for the management of adults with diabetes. Diabetes Care 2014;37(Suppl 1):S120–43. [4] Brand-Miller JC. Importance of glycaemic index in diabetes. Am J Clin Nutr 1994;59:747S–52S. [5] Delahanty LM, Halford BN. The role of diet behaviours in achieving improved glycaemic control in intensively treated patients in the Diabetes Control and Complications Trial. Diabetes Care 1993;16: 1453–8. [6] Al-Abouf M, Assaad-Khalil S, Buse J, Fahdil I, Fahmy M, Hafez S, et al. Recommendations for management of diabetes during Ramadan. Diabetes Care 2010;33:1895–902. [7] Havel RJ. Caloric homeostasis and disorders of fuel transport. N Engl J Med 1972;287:1186–92. [8] Dinneen S, Gerich J, Rizza R. Carbohydrate metabolism in non-insulindependent diabetes mellitus. N Engl J Med 1992;327:707–13.
[9] Monnier L. Is postprandial glucose a neglected cardiovascular risk factor in type 2 diabetes? Eur J Clin Invest 2000;30(Suppl 2):3–11. [10] Kaushal K, Raina SK. Risk approach strategy in diabetics on fasting evidence base through narrative review with a special focus on Ramadan fasting. J Soc Health Diabetes 2015;3:11–5. [11] El Aziz B, Skalli S, Chadli A, El Ghomari H, Farouqi A. Diabète et Ramadan : mise au point sur les recommandations récentes. Med Mal Metabol 2014;8:221–5. [12] DeFronzo RA. Pathogenesis of type 2 diabetes: metabolic and molecular implications for identifying diabetes genes. Diabetes Rev 1997;5:177–269. [13] Hollenbeck CB, Coulston AM, Reaven GM. Glycaemic effects of carbohydrates: a different perspective. Diabetes Care 1986;9:641–7. [14] Nuttall FQ, Mooradian AD, Gannon MC, Billington C, Krekowski P. Effect of protein ingestion on the glucose and insulin response to a standardized oral glucose load. Diabetes Care 1984;7:465–70. [15] Peters AL, Davidson MB. Protein and fat effects on glucose responses and insulin requirements in subjects with insulin-dependent diabetes. Am J Clin Nutr 1993;58:555–60. [16] Alkaabi JM, Al-Dabbagh B, Ahmad S, Saadi HF, Gariballa S, Al Ghazalli M. Glycaemic indices of five varieties of dates in healthy and diabetic subjects. Nutr J 2011;10:59. [17] Foster-Powell K, Holt SHA, Brand-Miller JC. International table of glycaemic index and glycaemic load values: 2002. Am J Clin Nutr 2002;76:5–56. [18] Monnier L, Colette C, Sardinoux M, Baptista G, Regnier-Zerbib A, Owens D. Frequency and severity of the dawn phenomenon in type 2 diabetes: relationship to age. Diabetes Care 2012;35:2597–9. [19] Monnier L, Colette C, Dejager S, Owens D. Magnitude of the dawn phenomenon and its impact on the overall glucose exposure in type 2 diabetes. Is this of concern? Diabetes Care 2013;36:4057–62. [20] Monnier L, Colette C, Dejager S, Owens D. The dawn phenomenon in type 2 diabetes. How to assess it clinical practice? Diabetes Metab 2014 [Epub ahead of print].
L. Monnier (MD) a,∗ F. Bonnet (MD) b C. Colette (PhD) a a Institute of Clinical Research, University of Montpellier, 641, avenue Doyen-Giraud, 34093 Montpellier cedex 5, France b Department of Endocrinology, University Hospital, 35200 Rennes, France ∗ Corresponding
author. Tel.: +33 411 98 91. E-mail address: [email protected] (L. Monnier) Received 12 November 2014 Accepted 13 November 2014 Available online 15 December 2014
ScienceDirect www.sciencedirect.com Diabetes & Metabolism 41 (2015) 1–4
Editorial
New insights on glucose homoeostasis during Ramadan
Keywords: Glucose homeostasis; Ramadan; Dietary intake
In this issue of Diabetes & Metabolism, Lessan et al. [1] report their experience in patients with diabetes (mostly type 2) who were investigated and compared during Ramadan and non-Ramadan periods. There is cogent evidence that Ramadan fasting disturbs the routine dietary habits of people with diabetes. As mentioned by Lessan et al. [1], the Ramadan fast entails a major shift in the timing and content of meals. It is currently admitted that, in normal conditions such as the absence of any intercurrent disease or illness, the nutrient intakes of people with diabetes should be closely similar to those recommended for the general population of healthy, non-diabetic individuals [2,3]. Weight-maintaining diets are usually prescribed for those who have body weights within the normal range, while calorierestricted diets are generally implemented in those who are overweight or obese [2,3]. In addition, dietary carbohydrates should be distributed throughout the day by spreading nutrient intakes over regular time intervals for the three main meals and, eventually, by additional snacking at mid-morning and/or mid-afternoon times and at bedtime as appropriate. In addition, by combining these dietary recommendations with better due consideration of the glycaemic index of foods [4], it has been demonstrated that it is possible to decrease HbA1c levels at least by 1% (one percentage point), even in those with type 1 diabetes being intensively treated with either insulin pumps or basal–bolus insulin regimens [5]. However, as mentioned above, all recommendations related to the quantity and quality of carbohydrates (the glycaemic load) are usually far from fulfilled during the Ramadan period, which is characterized by both abstinence from eating and drinking from dawn to sunset, and no food or fluid restriction between sunset and dawn [6]. The transition from the fasting to the refeeding period is marked by the consumption of a sunset meal that breaks the fasting state. In the United Arab Emirates, the content of this sunset (iftar) meal has been estimated to provide an average intake of energy and carbohydrates of 1400 kcal and 160 g, respectively [1]. Therefore, using continuous glucose monitoring, it http://dx.doi.org/10.1016/j.diabet.2014.11.005 1262-3636/© 2014 Elsevier Masson SAS. All rights reserved.
is not surprising that a sudden and steep rise in glucose levels was observed by Lessan et al. [1] in all subsets of patients, irrespective of the type of antidiabetic therapies used. 1. Metabolic homoeostasis during Ramadan and consequences for drug treatments After a 12- to 15-h fast, the usual duration of abstinence from eating and drinking during Ramadan, both non-diabetic and diabetic people enter the “real” fasting state after a stepwise transition throughout several metabolic stages [7–9]. The nocturnal eating period is followed by a postprandial state that begins with the last food intake, usually at dawn. During this nocturnal period, any dietary carbohydrates ingested are progressively hydrolysed in the intestines, absorbed as monosaccharides and poured into the systemic circulation for further metabolisation in extrahepatic tissues or stored in the liver as glycogen. Each 4-h postprandial period is followed by a 6-h postabsorptive state, which is metabolically characterized by progressive breakdown (glycogenolysis) of the glycogen stored in the liver during the preceding postprandial period [8,9]. Consequently, all those who have taken their last meal at dawn and not eaten during the daylight hours are in a genuine fasting state at the time of the sunset meal. This latter state is characterized by a progressive shift from glycogenolysis to gluconeogenesis (glucose derived from lactate, alanine and glycerol) and by an increased release of free fatty acids from adipose tissue and, subsequently, an increased production of ketone bodies (Fig. 1) [7]. In insulin-using diabetic patients, especially those with type 1 diabetes, such metabolic changes increase the risk of developing ketoacidosis. This complication does not arise in patients with type 2 diabetes treated with oral antidiabetic drugs (OADs), but it cannot be totally excluded in insulin-requiring patients with type 2 diabetes. Usually, in such patients, abstinence from eating during the daylight hours puts them at risk of either hypoglycaemic episodes or exaggerated hyperglycaemia, depending on whether the dosages of
2
Editorial / Diabetes & Metabolism 41 (2015) 1–4
Fig. 1. Utilization and production of metabolic fuel in normal, healthy people during the postabsorptive state and early starvation [7].
antidiabetic medications (sulphonylureas or insulin) have been insufficiently or excessively reduced [6]. For this reason, sulphonylureas are usually considered unsuitable during Ramadan. As a consequence, short-acting insulin secretagogues (glinides) or glucose-dependent insulinotropic agents [dipeptidyl peptidase (DPP)-4 inhibitors, glucagon-like peptide (GLP)1 receptor agonists] should serve as substitutes for ongoing therapy with long-acting non-glucose-dependent insulin secretagogues such as sulphonylureas [6,10]. In patients treated with insulin, however, it is usually recommended to reduce overall daily dosages and, more specifically, the doses injected at the dawn meal (suhoor) [11]. Furthermore, it is worth noting that the majority of the overall dose should be delivered before the sunset (iftar) meal [11] in patients treated with either twice-daily biphasic insulin regimens or multiple daily insulin injections. In the study by Lessan et al. [1], the overall daily dose of insulin was reduced by 8% during Ramadan. Given the fact that this apparently small reduction was able to maintain satisfactory glycaemic control, it raises the question of whether the usual advice to reduce insulin doses by 20–30%, as reported by Lessan et al. [1] and others [11], is not somewhat exaggerated. 2. A typical case report and its integration into general considerations for Ramadan In September 2008, we, at the outpatients’ clinics of the University Hospital (Montpellier, France), had the opportunity to investigate a subject on an ambulatory basis, using continuous glucose monitoring technology, during Ramadan. The subject’s daily glucose pattern (Fig. 2) was similar to those observed by Lessan et al. [1], including a dietary intake of carbohydrates at the sunset meal that was followed by a rapid and exaggerated increment in glucose levels. Within a time interval of < 2 h, glucose concentrations rose from 130 mg/dL to ≥ 400 mg/dL, and plateaued at an average level of 400 mg/dL overnight until dawn. During the Ramadan period, this patient, who was usually treated (in non-Ramadan periods) with a twice-daily insulin glargine regimen (58 and 20 units before breakfast and dinner, respectively) was instructed to take a single daily dose of insulin
just before the sunset meal, which combined 44 units of insulin glargine and 16 units of short-acting insulin glulisine. Yet, the potency of this high predinner dose of insulin to control blood glucose excursions after the sunset meal was largely annihilated and overcome by a carbohydrate intake that was probably too high a level for the sunset meal, and this high level was further maintained throughout the nocturnal period. At dawn and throughout the subsequent daylight hours, this patient continued to exhibit high circulating concentrations of glucose as a result of the continuous and sustained nocturnal overfeeding. To deal with this situation, the patient took a single dose of insulin (44 units of glargine and 16 units of glulisine) injected at the sunset meal several hours before the beginning of the diurnal period. As illustrated in Fig. 2, the rate of glucose disappearance was relatively constant throughout the period from 08h00 to 20h00, with a progressive glucose decrement from 400 to 130 mg/dL. The long delay required to obtain a near-normal glucose concentration in the late afternoon indicated that a single injection combining prandial and basal insulin analogues at the evening meal on the preceding day was not sufficient to achieve satisfactory 24-h glycaemic control in the face of frank nighttime overeating. Given the latter situation, it might be better to recommend a basal–bolus regimen with injection of an appropriate dose of a rapid insulin analogue before the dawn meal. Another alternative would be to use a twice-daily regimen combining the injection of basal and prandial insulin preparations at both the sunset and early-morning meals, especially when the latter also provides a significant intake of carbohydrates. In fact, according to our observations, it is highly likely that the carbohydrate loads at both the sunset and dawn meals largely exceeded the total body glucose-uptake capabilities (2 mg/kg/min) usually observed during the postabsorptive state in normal healthy people [12]. Bringing together our case report and the observations of Lessan et al. [1], it appears that both the exaggerated glucose excursions after the sunset meal and the sustained overnight hyperglycaemia are the two main glycaemic disorders encountered during Ramadan. However, the findings of Lessan et al. [1] appear to be somewhat reassuring as those investigators found that the impact of such glycaemic
Editorial / Diabetes & Metabolism 41 (2015) 1–4
3
Fig. 2. Continuous glycaemic profile during Ramadan of a patient with type 2 diabetes treated with a combination of long- and short-acting insulin preparations injected once daily before the sunset meal. The patient was also taking metformin and glibenclamide at 3 g/day and 10 mg/day, respectively.
disorders on the overall glycaemic control of patients with type 2 diabetes was rather small. For instance, in their population of diabetes patients considered as a whole, they observed that all parameters used to assess ambient hyperglycaemia (mean glucose value), glucose variability [mean amplitude of glycaemic excursion (MAGE)] and hypoglycaemic risk (proportion of time spent in hypoglycaemia) were not significantly different when non-Ramadan and Ramadan periods were compared [1]. Such results indicate that deterioration of diabetic control during the Ramadan fast can be prevented when structured recommendations are made to patients. In the study by Lessan et al. [1], recommendations were mainly focused on the titration of sulphonylureas and insulin, agents that bring hypoglycaemia risk. On the other hand, dietary advice was given in a somewhat casual manner, as the nutrient composition of the sunset meal was not precisely reported and only estimated from an average assessment based on the usual practice in the United Arab Emirates [1]. 3. Is dietary intake a major problem during Ramadan? While some people may perhaps have a tendency to minimize the role of dietary habits during Ramadan, there still remains the fact that the total amount of carbohydrates in the sunset meal (160 g, with one-third provided as simple sugars) was probably responsible for the exaggerated post-meal glucose surges observed by Lessan et al. Nevertheless, as there are wide intraand interindividual variations and marked differences across population groups in the nutrient contents of the sunset and dawn meals, this is cogent evidence that greater attention should be paid to both meals. First, carbohydrate-containing foods overall should be reduced and, second, foods with the highest content of simple sugars should be given at the end of the sunset meal, as it has been demonstrated that the intestinal absorption of high glycaemic loads is slower when carbohydrates are consumed along with proteins and fats in a mixed meal [13–15].
In particular, attention should also be paid to the glycaemic load (quantity and quality) of carbohydrate-containing foods [16] and the time at which they are given during the sunset meal. However, the glycaemic response to sunset meals containing various carbohydrates of different glycaemic indices has not been documented. Nevertheless, it is well known that Muslims break the fasting state by eating carbohydrate-containing foods that are easy to digest, such as dried dates. This habit usually has no impact on the post-meal glycaemic responses of healthy, non-diabetic individuals. In contrast, exaggerated blood glucose surges can occur in patients with diabetes when an excessive amount of dried dates is consumed at the sunset meal, as the carbohydrate content of this fruit is as high as 70 g per 100 g of edible parts and mostly as simple sugars, including mainly glucose and fructose along with small amounts of sucrose [16]. However, the content of crude fibre in dried dates is relatively high (2.5 g per 100 g), and it is well-known that crude fibre can attenuate glucose absorption. Thus, it is not surprising that, despite differences reported throughout the literature [17], the glycaemic index of dried dates has been estimated at 50% compared with the glucose reference [16]. In addition, at the sunset meal that breaks the fasting state during Ramadan, dried dates are usually consumed with dairy products (milk or thick yoghurt) that contribute by exerting an additional blunting effect on the glucose response. Consequently, the traditional breaking of the fast with dried dates mixed with milk products seems to be appropriate, provided that the amount of dried dates consumed at the sunset meal remains within reasonable limits. In conclusion, it appears that the religious fast at Ramadan results in marked changes in glucose homoeostasis in people with diabetes, especially those treated with insulin. The cornerstone of appropriate management of diabetic patients during this period should be mainly, but not solely, focused on better meal planning [6,10]. Special attention should be paid, first, to the carbohydrate content of the sunset meal in terms of both quantity and quality (glycaemic load) and, second, to eating habits throughout the nocturnal period. In addition, there is a mixed
4
Editorial / Diabetes & Metabolism 41 (2015) 1–4
message in that, while most healthcare professionals attempt to provide appropriate nutritional recommendations for the sunset meal, there is a tendency to be more lax in educating patients about controlling the dawn meal. The present review aims in part to remind people that excessive carbohydrate intakes at the dawn meal can have harmful effects on glycaemic control throughout the day, including an inordinately long delay in the disappearance rate of glucose from plasma. This is especially the case in those who exhibit the “dawn phenomenon”, a spontaneous early-morning rise in blood glucose [18–20]. In diabetics being treated with insulin, any pharmacological treatment should be carefully selected and titrated according to both the patient’s eating patterns and the physician’s own clinical practices. Disclosure of interest The authors declare that they have no conflicts of interest concerning this article. References [1] Lessan N, Hannoun Z, Hasan H, Barakat MT. Glucose excursions and glycaemic control during Ramadan fasting in diabetic patients: insights from continuous glucose monitoring (CGM). Diabetes Metab 2015 [Epub ahead of print]. [2] Franz MJ, Bantle JP, Beebe CA, Brunzell JD, Chiasson J-L, Garg A, et al. Evidence-based nutrition principles and recommendations for the treatment and prevention of diabetes and related complications. Diabetes Care 2002;25:148–98. [3] Evert AB, Boucher JL, Cypress M, Dunbar SA, Franz MJ, Mayer-Davis EJ, et al. Nutrition therapy recommendations for the management of adults with diabetes. Diabetes Care 2014;37(Suppl 1):S120–43. [4] Brand-Miller JC. Importance of glycaemic index in diabetes. Am J Clin Nutr 1994;59:747S–52S. [5] Delahanty LM, Halford BN. The role of diet behaviours in achieving improved glycaemic control in intensively treated patients in the Diabetes Control and Complications Trial. Diabetes Care 1993;16: 1453–8. [6] Al-Abouf M, Assaad-Khalil S, Buse J, Fahdil I, Fahmy M, Hafez S, et al. Recommendations for management of diabetes during Ramadan. Diabetes Care 2010;33:1895–902. [7] Havel RJ. Caloric homeostasis and disorders of fuel transport. N Engl J Med 1972;287:1186–92. [8] Dinneen S, Gerich J, Rizza R. Carbohydrate metabolism in non-insulindependent diabetes mellitus. N Engl J Med 1992;327:707–13.
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L. Monnier (MD) a,∗ F. Bonnet (MD) b C. Colette (PhD) a a Institute of Clinical Research, University of Montpellier, 641, avenue Doyen-Giraud, 34093 Montpellier cedex 5, France b Department of Endocrinology, University Hospital, 35200 Rennes, France ∗ Corresponding
author. Tel.: +33 411 98 91. E-mail address: [email protected] (L. Monnier) Received 12 November 2014 Accepted 13 November 2014 Available online 15 December 2014
