**1. Introduction**

422 Type 1 Diabetes – Complications, Pathogenesis, and Alternative Treatments

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> Type 1 diabetes mellitus is by far the most common metabolic and endocrinal disease in children (Peters & Schriger, 1997). The major dietary component responsible for fluctuations in blood glucose levels is carbohydrate. The amount, source (Jenkins et al., 1981; Gannon et al., 1989) and type (Brand et al., 1985) of carbohydrate appear to have profound influence on postprandial glucose levels. The chronic hyperglycemia of diabetes is associated with longterm damage, dysfunction and failure of various organs especially the eyes, kidneys, nerves, heart and blood vessels (American Diabetes Association, 2001).

> The glycemic effect of any foodstuff is defined as its effect on blood glucose level postprandially. Both the glycemic index (GI) and the peak incremental index (PII) are used to assess the glycemic effect of different food stuffs (Jenkins et al., 1981). Jennie et al (2003) who studied the use of low glycemic index diets in the management of diabetes found that diets with low glycemic indices (GI), compared with conventional or high-GI diets, improved overall glycemic control in individuals with diabetes, as assessed by glycemic index, peak incremental index, reduced HbA1c and fructosamine. They concluded that using low-GI foods in place of conventional or high-GI foods has a clinically useful effect on postprandial hyperglycemia similar to that offered by pharmacological agents that target postprandial hyperglycemia. Similarly, the American Diabetes Association (2002) stated that the use of low-GI foods may reduce postprandial hyperglycemia.

> Honey is the substance made when the nectar and sweet deposits from plants are gathered, modified and stored in the honeycomb by honey bees. It is composed primarily of the sugars glucose and fructose; its third greatest component is water. Honey also contains numerous other types of sugars, as well as acids, proteins and minerals (White et al., 1962; White, 1980; White, 1975). The water content of honey ranges between 15 to 20% (average 17.2%). Glucose and fructose, the major constituents of honey, account for about 85% of the honey solids. Besides, about 25 different sugars have been detected. The principal oligosaccharides in blossom honeys are disaccharides: sucrose, maltose, turanose, erlose. Trace amounts of tetra and pentasaccharides have also been isolated (Bogdanov, 2010). The protein and amino acid content of honey varies from 0.05 to 0.3 %. The honey proteins are mainly enzymes (White, 1975). Honey also contains varying amounts of mineral substances ranging from 0.02 to 1.03 g/100 g (White, 1975). Among honey benefits are its anti-

Honey and Type 1 Diabetes Mellitus 425

chemically on the Synchron CX5 autoanalyzer (Beckman instruments Inc.)1.

4. Calculation of glycemic and peak incremental indices (see example figure 3.1):

Area under glycemic curve of test food Glycemic index◌ً of the food Jenkins, 1987<sup>=</sup> Area under glycemic curve of glucose

 Area under curve (AUC) refers to the area included between the baseline and incremental blood glucose points when connected by straight lines. The area under each incremental glucose curve is calculated using the trapezoid rule (note: only areas above

 Peak incremental index (PII) (Samanta et al., 1985) is defined as the ratio of the maximal increment of plasma glucose produced by sugar to that produced by glucose

Maximal increment produced by the sugar tested Peak incremental index

Standard computer program SPSS for Windows, release 13.0 (SPSS Inc., USA) was used for data entry and analysis. All numeric variables were expressed as mean ± standard deviation (SD). Comparison of different variables in various groups was done using student t-test and Mann–Whitney test for normal and non-parametric variables, respectively. Wilcoxon signed

Maximal increment is the difference between the peak point and the fasting point.

Maximal increment produced by glucose

by interpolation from the calibration curve.

the baseline are used).

**3.3 Statistical analysis** 

1 Beckman: 2005, kraemerBLW, Brew, CA 92621, USA.

2 Biosource Europe S.A—Rue de lindustrie, 8-B-1400-Nivelles-Belgium.

3. Measurement of fasting and postprandial serum C- peptide level: Venous blood samples were withdrawn from each subject at 0 (fasting) and 2 h postprandial after ingestion of each individual sugar. The samples were then centrifuged and serum was stored in aliquots at – 20°C. At the end of the study, samples were calibrated for Cpeptide using the biosource c-pep-easia2, which is a solid phase enzyme amplified sensitivity immunoassay performed on a microtiter plate. A fixed amount of C-peptide labeled with horseradish peroxidase (HRP) competes with unlabeled C-peptide present in the calibrators controls and samples for a limited number of binding sites on a specific antibody. After 2 h incubation at room temperature, the microtiter plates were washed to stop the competition reaction. The chromogenic solution (TMB-H2O2) was added and incubated for 30 min. The reaction was stopped with the addition of stop solution, and the microtiter plate was then read at the appropriate wave length. The amount of substrate turnover was determined colorimetrically by measuring the absorbance which was inversely proportionate to the C-peptide concentration. A calibration curve was plotted and C-peptide concentration in samples was determined

random order, on separate mornings 1 week apart. The honey dose for each patient was calculated based on the fact that each 100 gm of the honey used in this study contained 77.3 gm sugars. So if a patient weighs for example 20 kg, he/she should receive 20 x 1.75 = 35 gm sugar which will be present in (35 x 100) ÷ 77.3 = 45.3 gm honey. Venous blood was sampled just before ingestion and then every 30 min postprandial for 2 h thereafter. Samples were left to clot, centrifuged and glucose assay was performed

inflammatory (Al Waili & Boni, 2003), anti- oxidant (Frankel et al., 1998; Gheldof & Engeseth, 2002; Gross et al., 2004) and anti-microbial effects (Molan, 1992; Steinberg et al., 1996; Molan, 1997; Theunissen et al., 2001). Further-more, several studies have shown that honey produced an attenuated postprandial glycemic response when compared with sucrose in both patients with diabetes and normal subjects (Ionescu-Tirgoviste et al., 1983; Shambaugh et al., 1990; Samanta et al., 1985; Al Waili, 2004; Agrawal et al., 2007).

C-peptide is considered to be a good marker of insulin secretion and has no biologic activity of its own (Ido et al., 1997). Measurement of C-peptide, however, provides a fully validated means of quantifying endogenous insulin secretion. C-peptide is co-secreted with insulin by the pancreatic cells as a by-product of the enzymatic cleavage of proinsulin to insulin. Consequently, serum C-peptide level can be used as a true indicator of any change in the insulin level, which is the main determinant of plasma glucose level.

Several studies were performed in healthy and in type 2 diabetic patients to evaluate the effects of honey on the insulin and C-peptide levels, and the results were controversial (Bornet et al., 1985; Elliott et al., 2002; Watford, 2002; Al-Waili, 2003).
