MANAGEMENT OF DIABETES IN RAMADAN

Management of patients with type 1 diabetes

In general, patients with type 1 diabetes, especially if “brittle” or poorly controlled, are at very high risk of developing severe complications and should be strongly advised to not fast during Ramadan. In addition, patients who are unwilling or unable to monitor their blood glucose levels multiple times daily are at high risk and should be advised to not fast.

It is currently recommended that treatment regimens aimed at intensive glycemia management be used in patients with diabetes. The DCCT and its follow-up, the EDIC (Epidemiology for Diabetes Interventions and Complications) study, have shown that intensive glycemia management is protective against microvascular complications and that the benefits are long lasting. Glycemic control at near-normal levels requires use of multiple daily insulin injections (three or more) or use of continuous subcutaneous insulin infusion through pump therapy. Close monitoring and frequent insulin dose adjustments in this setting are essential to achieve optimal glycemic control and avoid hypo- or hyperglycemia in patients with type 1 diabetes.

It is unlikely that one injection of intermediate- or long-acting insulin administered before the evening meal would provide adequate insulin coverage for 24 hours. Typically, patients will need to use two daily injections of NPH as intermediate-acting insulin, administered before the predawn and sunset meals, in combination with a short-acting insulin to cover food intake at the associated meals. However, there is an increased risk of hypoglycemia around midday due to peaking of the early morning insulin dose. Using the long-acting insulin ultralente is an option, with twice-daily injections at ∼12-h intervals to mimic basal insulin, and a rapid- or short-acting insulin should be added before the two meals. Still, ultralente cannot be considered truly basal insulin, since it has a broad peak of action at ∼8–14 h. Therefore, protracted hypoglycemia can occur, especially since ultralente exhibits wide variability in its duration of action (18–30 h).

Another option would be to use one daily injection of the long-acting insulin analog glargine or twice-daily injections of the insulin analog detemir along with premeal rapid-acting insulin analogs. Results of a study using insulin glargine in 15 relatively well-controlled patients with type 1 diabetes who fasted for 18 h showed that the mean plasma glucose declined from a value of 125 to 93 mg/dl during the fast. Two episodes of mild hypoglycemia occurred. Such a treatment regimen may be particularly useful since the duration of the fast in Ramadan is typically <18 h.

Clinical studies with other types of insulin during fasting are limited. A study on patients with type 1 diabetes using insulin lispro or insulin aspart instead of regular insulin in combination with intermediate-acting insulin injected twice a day led to improvement in postprandial glycemia and was associated with less hypoglycemic event. Subcutaneous insulin pump management is an appealing alternative strategy; however, it is more expensive and still requires frequent blood glucose monitoring.

Management of patients with type 2 diabetes

Diet-controlled patients.

In patients with type 2 diabetes who are well controlled with diet alone, the risk associated with fasting is quite low. However, there is still a potential risk for occurrence of postprandial hyperglycemia after the predawn and sunset meals if patients overindulge in eating. Distributing calories over two to three smaller meals during the nonfasting interval may help prevent excessive postprandial hyperglycemia. Patients controlled with diet alone usually combine this with a regular daily exercise program. The exercise program should be modified in its intensity and timing to avoid hypoglycemic episodes; the timing of the exercise could be changed to ∼2 h after the sunset meal. Finally, in this usually older age-group, often with hypertension and dyslipidemia, fluid restriction and dehydration may increase the risk of thrombotic events.

Patients treated with oral agents.

The choice of oral agents should be individualized. In general, agents that act by increasing insulin sensitivity are associated with a significantly lower risk of hypoglycemia than compounds that act by increasing insulin secretion.

·         Metformin. Patients treated with metformin alone may safely fast because the possibility of hypoglycemia is minimal. However, it is suggested that the timing of the doses be modified. We recommend that two thirds of the total daily dose be administered immediately before the sunset meal, while the other third be given before the predawn meal.

·         Glitazones. Patients on insulin sensitizers (rosiglitazone and pioglitazone) have a low risk of hypoglycemia. Usually no change in dose is required.

·         Sulfonylureas. This group of drugs was believed to be unsuitable for use during fasting because of the inherent risk of hypoglycemia. Hence, their use should be individualized and they should be utilized with caution. Use of chlorpropamide is absolutely contraindicated during Ramadan because of the high possibility of prolonged and unpredictable hypoglycemia. Newer members of the sulfonylurea family (gliclazide MR or glimepiride) have been shown to be effective, resulting in a lower risk of hypoglycemia. However, it should be emphasized that the above study did not include patients who fasted. In a recent study from Turkey, 52 patients with type 2 diabetes who fasted during Ramadan were managed with diet alone, sulfonylurea (glimepiride or gliclazide MR once daily), or repaglinide. One patient receiving a daily dose of 3 mg glimepiride developed a hypoglycemic event; the authors concluded that use of repaglinide might be safer than use of sulfonylureas. Body weight, fasting plasma glucose, fructosamine, A1C, and total cholesterol did not change during the study. Additional studies on the use of sulfonylureas in patients who fast during Ramadan are needed before strong recommendations on their utility can be made. Nevertheless, because of their worldwide use and relatively lower cost, these agents (especially the newer generations) may be used with caution.

·         Short-acting insulin secretagogues. Members of this group (repaglinide and nateglinide) are useful because of their short duration of action. They could be taken twice daily before the sunset and predawn meals. One study in patients with type 2 diabetes who fasted showed that use of repaglinide was associated with less hypoglycemia compared with glibenclamide.

Patients treated with insulin.

Problems facing patients with type 2 diabetes who administer insulin are similar to those with type 1 diabetes, except that the incidence of hypoglycemia is less. Again, the aim is to maintain necessary levels of basal insulin to remedy the prevailing relative deficiency and to overcome the existing insulin resistance. A major objective is to suppress hepatic glucose output to near-physiologic levels during the fasting period. Judicious use of intermediate- or long-acting insulin preparations plus a short-acting insulin administered before meals would be an effective strategy. Although hypoglycemia tends to be less frequent, it is still a risk, especially in patients who have required insulin therapy for a number of years, suggesting that β-cell failure has occurred and that a significant component of insulin deficiency exists. Very elderly patients with type 2 diabetes may be at especially high risk.

Using one injection of a long-acting insulin analog, such as insulin glargine, or two injections of NPH, lente, or detemir insulin before the sunset and predawn meals may provide adequate coverage as long as the dosage of each injection is appropriately individualized. A single injection of intermediate-acting insulin administered before the sunset meal may be sufficient to provide acceptable glycemic control in patients with reasonable basal insulin secretion. In such a situation, the peak action of intermediate insulin would be expected to occur at predawn and may provide adequate insulin coverage for that meal. However, most patients will still require short-acting insulin administered in combination with the intermediate- or long-acting insulin at the sunset meal to cover the large caloric load of Iftar. Moreover, many will need an additional dose of short-acting insulin at predawn. There is some evidence suggesting that use of insulin lispro instead of regular insulin before meals in patients with type 2 diabetes who fast during Ramadan is associated with less hypoglycemia and smaller postprandial glucose excursions. Again, as emphasized earlier, the overall dosage of medications, especially that of insulin, must be adjusted in conjunction with the weight loss or gain that may occur during Ramadan.