Breakfast replacement by a low-glycemic index liquid formula in patients with diabetes mellitus type 2

Fasting hyperglycemia and glucose intolerance are hallmarks of diabetes
mellitus type 2 and important treatment targets. The postprandial increase in
plasma glucose concentration is determined by the amount and rate of
carbohydrate absorption in relation to the amount amount of insulin secreted.
Reduction of carbohydrate absorption by replacing dietary carbohydrate with fat
effectively reduces both plasma glucose and insulin concentrations (1).
However, low-carbohydrate, high-fat diets have primarily been studied in the
context of a weight reduction strategy. Alternatively, replacement of dietary
carbohydrates by slowly absorbable carbohydrates, i.e. low glycemic index (GI)
food, can be used to reduce postprandial glucose. A recently conducted
randomized trial comparing a low and high GI diet in diet controlled patient
with DM2 indicated that a low GI diet reduced glucose C-reactive protein and
improved glucose tolerance, but had no effect on HbA1c or blood pressure (2).
In contrast, most of the older studies, summarized in two reviews (3,4)
suggested a favourable effect of low GI diets on glycemic control and plasma
lipids. The effect of a low GI diet intervention by replacing the regular
breakfast with a low GI liquid breakfast has not been studied before. Liquid
breakfasts are a relatively new phenomenon with growing popularity in our era
of pre-processed foods. In addition to the popularity and feasibility of a
liquid breakfast, it may also be more effective than replacement of lunch or
diner, because analyses of 24-hour glucose profiles in patients with DM2
revealed that post-prandial hyperglycemia is most pronounced after breakfast
(5). In this study we will determine the effect of regular breakfast
replacement by a low GI liquid breakfast on fasting and postprandial glucose
concentrations, long-term glycemic control and lipid metabolism.

Primary Objective: To determine the effect of breakfast replacement by a
low-glycemic index liquid meal on fasting and postprandial glucose and insulin
concentrations
Secondary Objective(s): To determine the effect of breakfast replacement by a
low-glycemic index liquid meal on body weight, HbA1c, glucose tolerance, plasma
lipid concentrations and oxidative stress.

The study is designed as a cross-over open-label intervention study. Fifty
patients with DM2 will be assigned to the intervention arm (low-GI breakfast)
or control arm (regular breakfast) for 3 months followed by a wash-out period
(no invention in either group) and cross-over to the other treatment arm

Isoenergetic replacement of regular whole-food breakfast by Glucerna SR
drinkvoeding (Abbott Laboratories B.V., Zwolle, Netherlands) will be compared
to regular whole-food breakfast

During the intervention participants will replace their usual breakfast by a
low-glycemic index liquid for 3 months and consume their regular breakfast for
another 3 months. All participants will meet with the investigator every 4
weeks (at home or in the AMC) to provide the liquid meals and to measure body
weight. Every 4 weeks 24-hour glucose profiles will be determined for 5 days
with a body worn subcutaneous glucose sensor, which will be calibrated 5 times
against a blood glucose measurement. A fasting venous blood sample will be
taken every 4 weeks. After 3 and 7 months participants will be admitted to the
clinical research unit for a 24-hour profile of plasma glucose and insulin
concentrations followed by an oral glucose tolerance test. The risks associated
with the nutritional intervention, continuous glucose monitoring and venous
blood sampling are negligible. The total volume of blood samples will not
exceed 450 mL.