**4. Results**

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

rank tests were used to compare multiple readings of the same variables. Chi-square (χ2) test was used to compare frequency of qualitative variables among the different groups

Fig. 3.1 Oral glucose tolerance curve of one of our patients

For calculation of the area under honey curve (AUC) =A1+A2+A3+A4

A2 is a trapezoid = 1/2 sum of the parallel sides (heights) x base

A3 is a trapezoid = 1/2 sum of the parallel sides (heights) x base

A4 is a trapezoid = 1/2 sum of the parallel sides (heights) x base

A1 is a triangle = 1/2 base x height = 1/2(X2 - X1) x (Y1 - X2) = ½(30) x (144 – 89) = 15 x 55 = 825

= 1/2[(Y1 - X2) + (Y2- X3)] ×(X4- X5) = 1/2[(144 – 89) + (225 – 89)] x 30 = 1/2(55 + 136) x 30 = 1/2(191) x 30 = 95.5 x 30 = 2865

= 1/2[(Y2 – X3) + (Y3- X4)] ×(X4- X3) = 1/2[(225 – 89) + (245 – 89)] x 30 = 1/2(136 + 156) x 30 = 1/2(292) x 30 = 146 x 30 = 4380

= 1/2[(Y3 – X4) + (Y4- X5)] ×(X3- X2) = 1/2[(245 – 89) + (128 – 89)] x 30 = 1/2(156 + 39) x 30 = 1/2(195) x 30 = 97.5 x 30 = 2925

AUC = A1 + A2 +A3 + A4 = 825 + 2865 + 4380 + 2925 = 10995

(Daniel, 1995).

No significant difference was found between patients (diabetics) and controls (nondiabetics) as regards the age and anthropometric measures (table 4.1). The mean age of subjects in the diabetic and non- diabetic groups was 11.3 and 8.5 years, respectively, with no statistically significant difference between groups (P > 0.05). The mean weight %, height % and body mass index did not also differ significantly between diabetics and nondiabetics (93.6%, 99.2%, 22.6 versus 94%, 98.2%, 23.1, respectively; P > 0.05). The mean plasma glucose level at 0 (fasting) and 30 min postprandial (i.e. 30 min after intake of glucose, sucrose or honey) did not differ significantly between subjects in both groups (diabetics and non-diabetics) (Tables 4.2 - 4.5) (P > 0.05). In non-diabetics (control), as shown in tables 4.2 and 4.3, the mean plasma glucose level 60, 90 and 120 min after intake of honey became significantly lower than after either glucose or sucrose (P< 0.05). Similarly, as shown in tables 4.4 and 4.5, there was a statistically significant decrease of plasma glucose in diabetics at 60, 90 and 120 min after honey intake, when compared with either glucose or sucrose (P< 0.05). The glycemic index (GI) and the peak incremental index (PII) of either sucrose or honey did not differ significantly between patients and controls (P > 0.05). On the other hand, both the GI and PII of honey were significantly lower when compared with sucrose in patients and controls. In non-diabetics, the glycemic index (GI) of honey was 0.69 compared to 1.32 for sucrose, with statistically significant difference (P< 0.05). In diabetics, the GI of honey was also significantly lower than that of sucrose (o.61 versus 1.19, respectively; P< 0.001) (table 4.6; figure 4.1). The PII of honey in non-diabetics was 0.61, compared to 1.25 for sucrose (P< 0.05). In diabetics, the PII of honey was also significantly lower than that of sucrose (0.60 versus 1.10, respectively; P< 0.001) (table 4.7; figure 4.2).

The mean (±SD) fasting C-peptide of patients and controls were 0.15 (±0.13) and 1.91 (±0.77) ng/ml, respectively (P< 0.001). All diabetic patients had a basal C-peptide level less than 0.7 ng/ml. In diabetics, although honey intake resulted in increase in the mean level of Cpeptide, yet this increase was not statistically significant when compared with either glucose or sucrose (P> 0.05) (Table 4.8; figure 4.3). On the other hand, in non-diabetics, honey produced a statistically significant higher C-peptide level, when compared with either glucose or sucrose (P< 0.05) (Table 4.8; figure 4.4).


P > 0.05 is non significant BMI: Body Mass Index

Table 4.1 Age and anthropometric measures in diabetics and non-diabetic controls (mean ± SD)

Honey and Type 1 Diabetes Mellitus 429

P < 0.05

Sucrose Honey P PII PII

Non- diabetics 1.25 (0.50–1.82) 0.61 (0.30–1.10) < 0.05 Diabetics 1.10 (0.65–2.98) 0.60 (0.20–1.60) < 0.001

Table 4.7 Peak incremental index (PII) mean (range) of sucrose and honey (peak incremental

P < 0.05

index of glucose = 1) (P < 0.05 is significant; P < 0.001 is highly significant)

Fig. 4.1 Glycemic index of sucrose and honey

Fig. 4.2 Peak incremental index of sucrose and honey


Table 4.2 Mean plasma glucose (±SD) (mg/dl) in non-diabetics (control) following equivalent amount of glucose or honey (P < 0.05 is significant)


Table 4.3 Mean plasma glucose (±SD) (mg/dl) in non-diabetics (control) following equivalent amount of sucrose or honey (P < 0.05 is significant)


Table 4.4 Mean plasma glucose (±SD) (mg/dl) in diabetics following equivalent amount of glucose or honey (P < 0.05 is significant)


Table 4.5 Mean plasma glucose (±SD) (mg/dl) in diabetics following equivalent amount of sucrose or honey (P < 0.05 is significant)


Table 4.6 Glycemic index (GI) mean (range) of sucrose and honey (glycemic index of glucose = 1) (P < 0.05 is significant; P < 0.001 is highly significant)

Time (min) Glucose Honey P 0 75.20 ± 17.45 72.30 ± 9.09 > 0.05 30 86.00 ± 19.88 83.30 ± 9.52 > 0.05 60 102.90 ± 24.47 88.80 ± 10.04 < 0.05 90 103.60 ± 21.24 88.50 ± 8.64 < 0.05 120 91.10 ± 20.74 81.00 ± 8.30 < 0.05

Table 4.2 Mean plasma glucose (±SD) (mg/dl) in non-diabetics (control) following

Table 4.3 Mean plasma glucose (±SD) (mg/dl) in non-diabetics (control) following

Time (min) Glucose Honey P 0 206.05 ± 95.79 208.10 ± 92.76 > 0.05 30 257.55 ± 92.79 247.75 ± 99.44 > 0.05 60 339.80 ± 96.86 285.50 ± 86.29 < 0.05 90 328.05 ± 99.75 272.25 ± 85.33 < 0.05 120 297.90 ± 106.86 236.75 ± 76.80 < 0.05 Table 4.4 Mean plasma glucose (±SD) (mg/dl) in diabetics following equivalent amount of

Time (min) Sucrose Honey P 0 198.30 ± 77.762 208.10 ± 92.76 > 0.05 30 268.25 ± 78.78 247.75 ± 99.44 > 0.05 60 320.35 ± 67.17 285.50 ± 86.29 < 0.05 90 323.65 ± 71.27 272.25 ± 85.33 < 0.05 120 310.15 ± 92.63 236.75 ± 76.80 < 0.05 Table 4.5 Mean plasma glucose (±SD) (mg/dl) in diabetics following equivalent amount of

Sucrose Honey

Non- diabetics 1.32 (0.85–1.92) 0.69 (0.43–1.43) < 0.05 Diabetics 1.19 (0.31–3.08) 0.61 (0.15–1.92) < 0.001 Table 4.6 Glycemic index (GI) mean (range) of sucrose and honey (glycemic index of glucose

GI GI P

Time (min) Sucrose Honey P 0 68.50 ± 12.59 72.30 ± 9.09 > 0.05 30 83.80 ± 13.56 83.30 ± 9.52 > 0.05 60 101.60 ± 11.45 88.80 ± 10.04 < 0.05 90 105.40 ± 18.03 88.50 ± 8.64 < 0.05 120 93.60 ± 17.25 81.00 ± 8.30 < 0.05

equivalent amount of glucose or honey (P < 0.05 is significant)

equivalent amount of sucrose or honey (P < 0.05 is significant)

glucose or honey (P < 0.05 is significant)

sucrose or honey (P < 0.05 is significant)

= 1) (P < 0.05 is significant; P < 0.001 is highly significant)

Fig. 4.1 Glycemic index of sucrose and honey


Table 4.7 Peak incremental index (PII) mean (range) of sucrose and honey (peak incremental index of glucose = 1) (P < 0.05 is significant; P < 0.001 is highly significant)

Fig. 4.2 Peak incremental index of sucrose and honey

Honey and Type 1 Diabetes Mellitus 431

As shown in many studies, sustained hyperglycemia is a risk factor for both micro vascular and macro vascular (as cardiovascular) complications in type 2 diabetes mellitus (Laakso & Lehto, 1997; Bretzel et al., 1998 as cited from Oizumi et al., 2007), while postprandial hyperglycemia has also been considered a risk factor for cardiovascular complications (Tominaga et al., 1999; Risso et al., 2001; Chiasson et al., 2002; Hanefeld et al., 2004; Nakagami et al., 2004 as cited from Oizumi et al., 2007). Many experimental and epidemiological studies have shown that increased postprandial plasma glucose levels may have equally or even more harmful effects than fasting hyperglycemia (Tominaga et al., 1999; Risso et al., 2001; Nakagami et al., 2004 as cited from Oizumi et al., 2007), and the reduction of postprandial plasma glucose levels delays the development of cardiovascular complications (Chiasson et al., 2002; Hanefeld et al., 2004 as cited from Oizumi et al., 2007). Jenkins (1987) defined the glycemic index as the ratio between the blood glucose areas produced after ingestion of a studied sugar compared to the blood glucose area produced after glucose ingestion itself. He stated that the glycemic response to food affects the insulin response which in turn is also potentiated by other non-glucose dependent factors in this food (Ostman et al., 2001). On the other hand, FAO/WHO (1998) defined the glycemic index as the incremental blood glucose area (0–2 h) following ingestion of 50 g of available carbohydrates (no fibers or resistant starch included), expressed as a percentage of the corresponding area following an equivalent amount of carbohydrate from a standard reference product. Samnata et al (1985) defined the peak incremental index of a certain sugar as the ratio between the maximal increments of the glucose level after ingestion of the sugar compared to the maximal increment produced after ingestion of glucose. He also mentioned that both the glycemic and the peak incremental indices are closely related, highly dependent and positively correlated to the plasma glucose produced after ingestion of any given sugar. Therefore, any change in the plasma glucose level after ingestion of a certain sugar will markedly affect both the glycemic index and the peak incremental index. Hence, the glycemic and the peak incremental indices measure how fast and how much a food raises blood glucose levels. Foods with higher index values raise blood sugar more rapidly than foods with lower index values do in case of the glycemic index and much more in case

In our study, no statistically significant differences were found between diabetic patients and non-diabetic controls regarding the glycemic and the peak incremental indices of the studied sugars. Similarly, Samnata et al (1985), who studied the glycemic effect of glucose, sucrose and honey in 12 normal volunteers, eight patients with insulin-dependent diabetes mellitus (IDDM) and six patients with non-insulin-dependent diabetes mellitus (NIDDM), found no significant differences between the normal volunteers and diabetic patients regarding the glycemic and peak incremental indices of both sugars. Since the glycemic index (GI) is the ratio between the area under curve (AUC) of the studied sugar and the AUC of glucose, and the peak incremental index (PII) is the ratio between the maximal blood glucose increment of the studied sugar and that of glucose; it may be expected that both GI and PII will be the same in both diabetics and non-diabetics. Our study showed that honey has statistically significant lower glycemic and peak incremental indices than sucrose and glucose in both patients and controls (< 1 with honey, 1 with glucose being the reference sugar and >1 with sucrose). In agreement, Kaye et al (2002), who published the international table of glycemic index and glycemic load values, found that the GI of honey (0.55 ± 0.05) was lower than that of sucrose (1.10 ± 0.21). Also, Shambaugh et al (1990) found that sucrose caused higher blood sugar readings than honey in normal volunteers. In the study of

**5. Discussion** 

of peak incremental index.


Table 4.8 Mean C-peptide (±SD) (ng/ml) following equivalent amount of glucose, sucrose or honey in non-diabetics and diabetics (P < 0.05 is significant)

Fig. 4.3 C-peptide following equivalent amount of glucose, sucrose or honey in diabetics

Fig. 4.4 C-peptide following equivalent amount of glucose, sucrose or honey in non-diabetics

### **5. Discussion**

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

Group C-peptide (ng/ml) P After glucose After sucrose After honey Non-diabetics 3.96 ± 0.84 3.99 ± 1.10 5.50 ± 1.15 P < 0.05 Diabetics 0.29 ± 0.53 0.32 ± 0.53 0.47 ± 1.09 P > 0.05 Table 4.8 Mean C-peptide (±SD) (ng/ml) following equivalent amount of glucose, sucrose or

Fig. 4.3 C-peptide following equivalent amount of glucose, sucrose or honey in diabetics

Fig. 4.4 C-peptide following equivalent amount of glucose, sucrose or honey in non-diabetics

honey in non-diabetics and diabetics (P < 0.05 is significant)

As shown in many studies, sustained hyperglycemia is a risk factor for both micro vascular and macro vascular (as cardiovascular) complications in type 2 diabetes mellitus (Laakso & Lehto, 1997; Bretzel et al., 1998 as cited from Oizumi et al., 2007), while postprandial hyperglycemia has also been considered a risk factor for cardiovascular complications (Tominaga et al., 1999; Risso et al., 2001; Chiasson et al., 2002; Hanefeld et al., 2004; Nakagami et al., 2004 as cited from Oizumi et al., 2007). Many experimental and epidemiological studies have shown that increased postprandial plasma glucose levels may have equally or even more harmful effects than fasting hyperglycemia (Tominaga et al., 1999; Risso et al., 2001; Nakagami et al., 2004 as cited from Oizumi et al., 2007), and the reduction of postprandial plasma glucose levels delays the development of cardiovascular complications (Chiasson et al., 2002; Hanefeld et al., 2004 as cited from Oizumi et al., 2007). Jenkins (1987) defined the glycemic index as the ratio between the blood glucose areas produced after ingestion of a studied sugar compared to the blood glucose area produced after glucose ingestion itself. He stated that the glycemic response to food affects the insulin response which in turn is also potentiated by other non-glucose dependent factors in this food (Ostman et al., 2001). On the other hand, FAO/WHO (1998) defined the glycemic index as the incremental blood glucose area (0–2 h) following ingestion of 50 g of available carbohydrates (no fibers or resistant starch included), expressed as a percentage of the corresponding area following an equivalent amount of carbohydrate from a standard reference product. Samnata et al (1985) defined the peak incremental index of a certain sugar as the ratio between the maximal increments of the glucose level after ingestion of the sugar compared to the maximal increment produced after ingestion of glucose. He also mentioned that both the glycemic and the peak incremental indices are closely related, highly dependent and positively correlated to the plasma glucose produced after ingestion of any given sugar. Therefore, any change in the plasma glucose level after ingestion of a certain sugar will markedly affect both the glycemic index and the peak incremental index. Hence, the glycemic and the peak incremental indices measure how fast and how much a food raises blood glucose levels. Foods with higher index values raise blood sugar more rapidly than foods with lower index values do in case of the glycemic index and much more in case of peak incremental index.

In our study, no statistically significant differences were found between diabetic patients and non-diabetic controls regarding the glycemic and the peak incremental indices of the studied sugars. Similarly, Samnata et al (1985), who studied the glycemic effect of glucose, sucrose and honey in 12 normal volunteers, eight patients with insulin-dependent diabetes mellitus (IDDM) and six patients with non-insulin-dependent diabetes mellitus (NIDDM), found no significant differences between the normal volunteers and diabetic patients regarding the glycemic and peak incremental indices of both sugars. Since the glycemic index (GI) is the ratio between the area under curve (AUC) of the studied sugar and the AUC of glucose, and the peak incremental index (PII) is the ratio between the maximal blood glucose increment of the studied sugar and that of glucose; it may be expected that both GI and PII will be the same in both diabetics and non-diabetics. Our study showed that honey has statistically significant lower glycemic and peak incremental indices than sucrose and glucose in both patients and controls (< 1 with honey, 1 with glucose being the reference sugar and >1 with sucrose). In agreement, Kaye et al (2002), who published the international table of glycemic index and glycemic load values, found that the GI of honey (0.55 ± 0.05) was lower than that of sucrose (1.10 ± 0.21). Also, Shambaugh et al (1990) found that sucrose caused higher blood sugar readings than honey in normal volunteers. In the study of

Honey and Type 1 Diabetes Mellitus 433

fructose produced a smaller postprandial insulin excursions than did consumption of glucosecontaining carbohydrates (Glinsmann & Bowman, 1993). Also, Watford et al (2002) stated that very small amounts of fructose, which is the main component of honey, could increase hepatic glucose uptake and glycogen storage, as well as reduce peripheral glycemia and thus insulin levels. Ionescu-Tirgoviste et al (1983) studied the blood glucose and plasma insulin responses to some simple carbohydrates (glucose, fructose, lactose) and some complex ones (apples, potatoes, bread, rice, carrots and honey) in 32 type 2 (non-insulin-dependent) diabetic patients, and they found that increases in plasma insulin were significantly higher after the more refined carbohydrates (glucose, fructose and lactose) than after the more complex ones (apples,

We hypothesize that honey might have a direct stimulatory effect on the healthy beta cells of pancreas; an effect which may be related to the non-sugar part of honey. This hypothesis is based on the finding that honey caused significant postprandial increase in the C-peptide level despite its lower glycemic and peak incremental indices when compared to either glucose or sucrose. On the other hand, the lack of significant increase in C-peptide levels among diabetic patients might be due to the minimal residual function of the patient's pancreatic beta cells, which is beyond their capacity of further postprandial response. This proposal is backed up by the findings of Pozzan et al (1997) who investigated the relation between the fasting C-peptide level and the ability to respond to a particular stimulus, and they reported that there is a positive significant correlation between the basal value (BV) and the peak value (PV) of C-peptide in insulin dependent diabetic patients and that positive responses need a minimal basal level of 0.74 ng/ml. In all our studied patients, the basal Cpeptide level was less than 0.7 ng/ml. Also other authors found significant correlations between the basal and the maximum C-peptide values after a stimulus. However, they reported different basal values which can respond to stimulation. Such values were 0.09 (Clarson et al., 1987), 0.18 (Eff et al., 1989) and 0.39 ng/ml (Faber & Binder, 1977). The variation in these levels was probably due to the different ages and different diabetes

1. Honey has a lower glycemic and peak incremental indices compared to glucose and sucrose in both type 1 diabetic patients and non-diabetics. Therefore, we recommend

2. In spite of its significantly lower glycemic and peak incremental indices, honey caused significant post- prandial rise of plasma C-peptide levels when compared to glucose and sucrose in non-diabetics; indicating that honey may have a direct stimulatory effect on the healthy beta cells of pancreas. On the other hand, C-peptide levels were not significantly elevated after honey ingestion when compared with either glucose or sucrose in type 1 diabetic patients. Whether or not ingestion of honey in larger doses or/and for an extended period of time would have a significant positive effect on the

Agrawal, O.; Pachauri, A.; Yadav, H.; Urmila, J.; Goswamy, H.; Chapperwal, A.; Bisen, P. &

Prasad, G. (2007). Subjects with impaired glucose tolerance exhibit a high degree of

potatoes, rice, carrots and honey, P less than 0.01).

duration of the studied populations (Pozzan et al., 1997).

using honey as a sugar substitute in type 1 diabetic patients.

**6. Conclusions and recommendations** 

diseased beta cells, needs further studies.

tolerance to honey. J Med Food 10(3):473–478

**7. References** 

Samnata et al (1985), honey ingestion in both diabetics (IDDM) and non-diabetics also resulted in a significantly lower PII compared to the glucose and sucrose. In the study done byAl-Waili (2004), honey compared with dextrose and sucrose caused a lower elevation of

plasma glucose levels (PGL) in both diabetics (IDDM) and normal subjects. In an attempt to explain his results, he stated that the mild reduction of plasma glucose levels obtained by honey might be a result of the fructose content of honey which requires metabolic transformation in the liver, a slow process conferring relatively low-GI on these sugars (Jenkins et al., 1981; Wolever et al., 1991). Also, Watford (2002) demonstrated that very small amounts of fructose, which is the main component of honey, could increase hepatic glucose uptake and glycogen storage, as well as reduce peripheral glycemia which could be beneficial in diabetic patients. In the study performed by Agrawal et al (2007), honey was found to produce an attenuated postprandial glycemic response especially in subjects with glucose intolerance. They referred these results to the possibility that the glucose component of honey might be poorly absorbed from the gut epithelium. Also, Tirgoviste et al (1983) studied blood glucose and plasma insulin responses to various carbohydrates in type 2 diabetes, and they found that the increase in plasma glucose was significantly higher after administration of more refined carbohydrates such as glucose than after the complex ones such as honey. Meanwhile, Oizumi et al (2007) and Arai et al (2004) found that consumption of a palatinose (a disaccharide found in honey)-based balanced formula suppressed postprandial hyperglycemia, glycemic and peak incremental indices and produced beneficial effects on the metabolic syndrome–related parameters (namely, the lipid profile and visceral fat accumulation) in diabetic patients. They stated the reason of this observation to be due to the fact that although palatinose is completely absorbed, yet it has the specific characteristics of delayed digestion and absorption as reported by Dahlquist et al (1963) and Lina et al (2002).

Our results showed that honey, compared to glucose and sucrose, caused a significant elevation in the C-peptide levels in non-diabetic subjects. Meanwhile, in diabetic patients, the plasma C-peptide levels did not differ significantly between the three types of sugars. To our knowledge, no similar work was done to study the effects of honey on C-peptide levels in type 1 diabetes mellitus. However, 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. In the study of Al Waili (2003), inhalation of honey solution, when compared with hyperosmolar dextrose and hypoosmolar distilled water, resulted in a significant elevation of plasma insulin and C-peptide in both normal individuals and in patients with type 2 diabetes mellitus. However, in 2004, the same author found that honey ingestion, when compared with sucrose, caused a greater elevation of insulin and C-peptide in type 2 diabetic patients, while in healthy subjects dextrose ingestion caused a significant elevation of plasma insulin and C-peptide when compared with honey. The author hypothesized that honey may have the ability to stimulate insulin production and secretion from the pancreas than do sucrose in type 2 diabetes mellitus. On the other hand, Bornet et al (1985) reported no significant changes in plasma insulin levels after honey ingestion compared to sucrose in type 2 diabetics. Liljeberg et al (1999) found that high-GI foods induced a greater elevation of blood insulin than did low glycemic index meals (like honey). Elliott et al (2002) tried to explore whether fructose consumption might be a contributing factor to the development of obesity and the accompanying metabolic abnormalities observed in the insulin resistance syndrome and they found that honey intake caused a significant lowering of plasma insulin and C-peptide in normal subjects when compared to sucrose and dextrose. They related their findings to the fructose content of honey which does not stimulate insulin secretion from pancreatic beta cells and that consumption of foods and beverages containing

Samnata et al (1985), honey ingestion in both diabetics (IDDM) and non-diabetics also resulted in a significantly lower PII compared to the glucose and sucrose. In the study done byAl-Waili (2004), honey compared with dextrose and sucrose caused a lower elevation of plasma glucose levels (PGL) in both diabetics (IDDM) and normal subjects. In an attempt to explain his results, he stated that the mild reduction of plasma glucose levels obtained by honey might be a result of the fructose content of honey which requires metabolic transformation in the liver, a slow process conferring relatively low-GI on these sugars (Jenkins et al., 1981; Wolever et al., 1991). Also, Watford (2002) demonstrated that very small amounts of fructose, which is the main component of honey, could increase hepatic glucose uptake and glycogen storage, as well as reduce peripheral glycemia which could be beneficial in diabetic patients. In the study performed by Agrawal et al (2007), honey was found to produce an attenuated postprandial glycemic response especially in subjects with glucose intolerance. They referred these results to the possibility that the glucose component of honey might be poorly absorbed from the gut epithelium. Also, Tirgoviste et al (1983) studied blood glucose and plasma insulin responses to various carbohydrates in type 2 diabetes, and they found that the increase in plasma glucose was significantly higher after administration of more refined carbohydrates such as glucose than after the complex ones such as honey. Meanwhile, Oizumi et al (2007) and Arai et al (2004) found that consumption of a palatinose (a disaccharide found in honey)-based balanced formula suppressed postprandial hyperglycemia, glycemic and peak incremental indices and produced beneficial effects on the metabolic syndrome–related parameters (namely, the lipid profile and visceral fat accumulation) in diabetic patients. They stated the reason of this observation to be due to the fact that although palatinose is completely absorbed, yet it has the specific characteristics of delayed digestion and absorption as reported by Dahlquist et al (1963) and Lina et al (2002). Our results showed that honey, compared to glucose and sucrose, caused a significant elevation in the C-peptide levels in non-diabetic subjects. Meanwhile, in diabetic patients, the plasma C-peptide levels did not differ significantly between the three types of sugars. To our knowledge, no similar work was done to study the effects of honey on C-peptide levels in type 1 diabetes mellitus. However, 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. In the study of Al Waili (2003), inhalation of honey solution, when compared with hyperosmolar dextrose and hypoosmolar distilled water, resulted in a significant elevation of plasma insulin and C-peptide in both normal individuals and in patients with type 2 diabetes mellitus. However, in 2004, the same author found that honey ingestion, when compared with sucrose, caused a greater elevation of insulin and C-peptide in type 2 diabetic patients, while in healthy subjects dextrose ingestion caused a significant elevation of plasma insulin and C-peptide when compared with honey. The author hypothesized that honey may have the ability to stimulate insulin production and secretion from the pancreas than do sucrose in type 2 diabetes mellitus. On the other hand, Bornet et al (1985) reported no significant changes in plasma insulin levels after honey ingestion compared to sucrose in type 2 diabetics. Liljeberg et al (1999) found that high-GI foods induced a greater elevation of blood insulin than did low glycemic index meals (like honey). Elliott et al (2002) tried to explore whether fructose consumption might be a contributing factor to the development of obesity and the accompanying metabolic abnormalities observed in the insulin resistance syndrome and they found that honey intake caused a significant lowering of plasma insulin and C-peptide in normal subjects when compared to sucrose and dextrose. They related their findings to the fructose content of honey which does not stimulate insulin secretion from pancreatic beta cells and that consumption of foods and beverages containing fructose produced a smaller postprandial insulin excursions than did consumption of glucosecontaining carbohydrates (Glinsmann & Bowman, 1993). Also, Watford et al (2002) stated that very small amounts of fructose, which is the main component of honey, could increase hepatic glucose uptake and glycogen storage, as well as reduce peripheral glycemia and thus insulin levels. Ionescu-Tirgoviste et al (1983) studied the blood glucose and plasma insulin responses to some simple carbohydrates (glucose, fructose, lactose) and some complex ones (apples, potatoes, bread, rice, carrots and honey) in 32 type 2 (non-insulin-dependent) diabetic patients, and they found that increases in plasma insulin were significantly higher after the more refined carbohydrates (glucose, fructose and lactose) than after the more complex ones (apples, potatoes, rice, carrots and honey, P less than 0.01).

We hypothesize that honey might have a direct stimulatory effect on the healthy beta cells of pancreas; an effect which may be related to the non-sugar part of honey. This hypothesis is based on the finding that honey caused significant postprandial increase in the C-peptide level despite its lower glycemic and peak incremental indices when compared to either glucose or sucrose. On the other hand, the lack of significant increase in C-peptide levels among diabetic patients might be due to the minimal residual function of the patient's pancreatic beta cells, which is beyond their capacity of further postprandial response. This proposal is backed up by the findings of Pozzan et al (1997) who investigated the relation between the fasting C-peptide level and the ability to respond to a particular stimulus, and they reported that there is a positive significant correlation between the basal value (BV) and the peak value (PV) of C-peptide in insulin dependent diabetic patients and that positive responses need a minimal basal level of 0.74 ng/ml. In all our studied patients, the basal Cpeptide level was less than 0.7 ng/ml. Also other authors found significant correlations between the basal and the maximum C-peptide values after a stimulus. However, they reported different basal values which can respond to stimulation. Such values were 0.09 (Clarson et al., 1987), 0.18 (Eff et al., 1989) and 0.39 ng/ml (Faber & Binder, 1977). The variation in these levels was probably due to the different ages and different diabetes duration of the studied populations (Pozzan et al., 1997).

### **6. Conclusions and recommendations**


#### **7. References**

Agrawal, O.; Pachauri, A.; Yadav, H.; Urmila, J.; Goswamy, H.; Chapperwal, A.; Bisen, P. & Prasad, G. (2007). Subjects with impaired glucose tolerance exhibit a high degree of tolerance to honey. J Med Food 10(3):473–478

Honey and Type 1 Diabetes Mellitus 435

Faber, O. & Binder, C. (1977). B-cell function and blood glucose control in insulin dependent diabetes within the first month of insulin treatment. Diabetologia 13:263–268 FAO/WHO. (1998). Carbohydrates in human nutrition (Paper No. 66). Food and Agricultural Organization and Geneva, World Health Organization, Rome Frankel, S.; Robinson, G. & Berenbaum, M. (1998). Antioxidant capacity and correlated

Gannon, M.; Nuttall, F.; Westphal, S.; Neil, B. & Seaquist, E. (1989). Effects of dose of

Gheldof, N. & Engeseth, N. (2002). Antioxidant capacity of honeys from various floral

Glinsmann, W. & Bowman, B. (1993). The public health significance of crystalline fructose,

Gross, H.; Polagruto, J.; Zhu, Q.; Kim, S.; Schramm, D. & Keen, C. (2004). Effect of honey

Hanefeld, M.; Cagatay, M.; Petrowitsch, T.; Neuser, D.; Petzinna, D. & Rupp, M. (2004).

Ido, Y.; Vindigni, A. & Chang, K. (1997). Prevention of vascular and neural dysfunction in

Ionescu-Tirgoviste, C.; Popa, E.; Sintu, E.; Mihalache, N.; Cheta, D. & Mincu, I. (1983). Blood

Jenkins, D. (1987). The glycemic index and the dietary treatment of hypertriglyceridemia

Jenkins, D.; Wolever, T.; Taylor, R.; Barker, H.; Fielden, H.; Baldwin, J.; et al (1981). Glycemic

Jennie, B.; Hayne, S.; Petocz, P. & Stephen, C. (2003). Low-glycemic index diets in the

Kaye, F.; Holt, S. & Janette, C. (2002). International table of glycemic index and glycemic

Laakso, M. & Lehto, S. (1997). Epidemiology of macrovascular disease in diabetes. J Diabetes

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**21** 

*Hungary* 

**Fatty Acid Supply in Pregnant Women** 

Long-chain polyunsaturated fatty acids (LCPUFAs) play an important role in the human body in building up cell membranes and in regulating their fluidity. The most important fatty acids are the essential n-3 fatty acid, alpha-linolenic acid (C18:3n-3, ALA) and the essential n-6 fatty acid, linoleic acid (C18:2n-6, LA), and their most important metabolites, docosahexaenoic acid (C22:6n-3, DHA) and arachidonic acid (C20:4n-6, AA). LCPUFAs are precursors of different eicosanoids, and their availability may be disturbed in several diseases. As insulin is one of the most potent activators of -6 desaturase enzyme, type 1 diabetes mellitus (T1DM) is characterised by the diminished levels of n-3 LCPUFAs (Decsi

Polyunsaturated fatty acids (PUFAs) are components of the lipid bilayer of cell membranes, where they also regulate membrane fluidity. Cell membranes containing more saturated fatty acids and cholesterol are more rigid, while PUFAs increase their fluidity as well as the number of receptors and their affinity to their substrates, like hormones and growth factors

PUFAs are also precursors of several second messengers. From the n-6 group, especially from AA proinflammatory eicosanoids are synthesized, while the n-3 fatty acids, especially eicosapentaenoic acid (C20:5n-3, EPA) are precursors of antiinflammatory eicosanoids. The n-6 essential fatty acid (EFA), LA plays an important role in the maintenance of the epidermal water barrier (Koletzko & Rodriguez-Palmero, 1999), preventing thereby the transepidermal water loss and epidermal damage (Yen et al., 2008). There are data indicating that LA also lowers plasma total cholesterol levels (Nikkari et al., 1983). In an animal study the n-3 EFA, ALA lowered serum and liver triacylglycerol levels, while it

AA and DHA play an important role in the maturation of the developing nervous system: during the third trimester and in the first months of life there is an increased incorporation into the fetal/neonatal brain and retinal membranes (Farquharson et al., 1992; Martinez &

Fish oil, containing EPA and DHA, may be beneficial not only during infancy, but also during adulthood. It may prevent the development of macula degeneration (Chua et al.,

**1. Introduction** 

(Das, 2006).

Mougan, 1998).

et al., 2002, 2007; Szabó et al., 2010b).

**2. Role of polyunsaturated fatty acids** 

increased serum HDL-cholesterol levels (Murano et al., 2007).

**with Type 1 Diabetes Mellitus** 

*University of Pécs, Department of Pediatrics, Pécs* 

Éva Szabó, Tamás Marosvölgyi and Tamás Decsi

