Background: Fructose 2,6 bisphosphate the powerful stimulator of phosphofructosekinase-1, is involved in the control of glycolysis, gluconeogenesis. Experimental and clinical surveies have demonstrated that degrees of fructose 2,6 bisphosphate increased in peripheral blood mononuclear cells in diabetics suggest that perturbation in immune cells play a major function in increased susceptibleness to infection. These altered metabolic merchandises and oxydated emphasis may play a function in the development of diabetic carbon monoxide mplication.
Aim: The present research is designed to analyze the consequence of fasting blood sugar and HbA1c on fructose 2,6 bisphosphate in diabetics and comparing and correlating the same parametric quantity with control topics.
Material and Methods: Two hundred patients with type-II diabetes and fifty control topics were selected for this survey. Fasting blood sugar and glycated haemoglobins were estimated. Fructose 2,6 bisphosphate was estimated and correlated from peripheral blood mononuclear cells.
Consequence: Consequences of this survey showed extremely important fructose 2,6 bisphosphate degrees in immune cells in diabetic group. A significantly positive correlativity of fructose 2,6 bisphosphate with FBS and HbA1c was seen in diabetic group.
Decision: Higher degrees of FBS and HbA1c are associated with increased degrees of fructose 2,6 bisphosphate of peripheral blood mononuclear cells in diabetes reduces unsusceptibility.
Fructose 2, 6 bisphosphate is detected in all mammalian tissue every bit good as in Fungi and plants.1 Fructose 2,6 bisphosphate is powerful positive allosteric effecter of phosphofructokinase-1 which is rate restricting enzyme for glycolysis.2 Fructose 2,6 bisphosphate is formed by phosphofructokinase-2. Phosphofructokinase-2 is a bifunctional protein that has both, the kinase activity that produces fructose 2,6 bisphosphate and phosphatase activity that converts fructose 2,6 bisphosphate back to fructose 6 phosphate and inorganic phosphate ( Pi ) .3 High fructose 2,6-bisphosphate degrees mediate enhanced glycolysis and bifunctional enzyme phosphofructokinase-2/fructose 2,6-bisphosphatase catalyses the formation and debasement of fructose 2,6-bisphosphate.4 Diabetes causes significant alterations in the fructose 2,6-bisphosphate system. In hepatocyte, diabetes mellitus enhances phosphorylation of fructose 2,6-bisphosphate taking to a lessening in the activity of the enzyme doing hyperglycaemia. In peripheral blood lymph cells fructose 2,6-bisphosphate system is somewhat different from that of hepatocyte.5 Hyperglycemia increases intracellular fructose 2,6-bisphosphate in immune cells.6 These findings may assist to clear up the impaired maps in immune cell, in patients with diabetes.7 As diabetes progress patients are at increased hazard of developing infections. Complication due to down unsusceptibility patient with diabetes mellitus has infections more frequently so those with diabetes mellitus. The class of the infection is besides more complicated in these patients.8 Good metabolic control is a major factor in restricting the development and spread of infection and most significantly, the development of diabetes complication predispose to infection.9 These factors include familial susceptibleness to infection, altered cellular humoral immune defence mechanism and local factor including hapless blood supply and nervus harm and changes in metamorphosis associated with diabetes mellitus.10 Haemoglobin A1c ( HbA1c ) is widely used to find degrees of long-run blood glucose, justice the adequateness of diabetes direction, and adjust therapies.11 Systematically high HbA1c degrees increase the hazard for long-run disabling and potentially dangerous complications, including cardiovascular disease, kidney disease, oculus harm and nervus damage.6 A important relation ship has been seen in some surveies between intracellular fructose 2,6- bisphosphate degrees and long term glycemic control as assessed by HbA1c.12
In present survey, accent has been given to gauge the degree of fructose 2, 6 bisphosphate, which impaired immune systems in lymph cell, has an deduction for result of the infection and correlative with HbA1c to cut down dangerous complications in diabetes.
A sum of two hundred and 50 topics were included in this survey. Two 100 topics were diagnosed type-II diabetics and 50 persons selected as control were wholly symptomless. In all instances age, sex, weight, tallness and continuance of unwellness were recorded. Diagnosed type-II diabetic patients were taken from diabetic clinics JPMC Karachi. About 8ml of blood was taken after an over dark fast. Peripheral mononucleate cells ( PBMC ) were separated by ficoll gradients from 6ml of venous blood. PBMC were homogenized in 50mM NaOH and incubated at 80a-¦C for 10mins. After centrifugation the supernatants were used to assay for fructose 2,6 bisphosphate by Van Schaftigen method.13 The serum glucose was estimated by kit method supplied by Spinreact SA Spain. HbA1c was estimated by fast ion exchange resins separation method utilizing the kit supplied by Human Germany. Statistically analysis was performed with SPSS 15.0 package.
Two hundred and 50 topics studied and distributed as 50 healthy normal topics as control group and two hundred diagnosed type-II diabetes mellitus. Table-1 shows mean values with standard mistake of mean ( meanA±s.e.m ) . Age, tallness, weight and organic structure mass index of control compared with diabetic topics. Height, weight and organic structure mass index of diabetics were significantly higher when compared to command. No statistically important difference observed in age. Table-2 shows the intergroup comparing of fasting blood glucose, glycated haemoglobin and fructose 2,6 bisphosphate. The average values of fasting blood glucose of diabetics were significantly higher ( P & lt ; 0.001 ) when compared to command. Similar consequences were found with HbA1c and fructose 2, 6 bisphosphate of diabetic group was significantly higher ( P & lt ; 0.001 ) when compared to command group. Table-3 depicts the comparing of relationship of fructose 2, 6 bisphosphate and serum fasting blood glucose and Co-efficient of correlativity “ R ” of fructose 2, 6 bisphosphate with HbA1c showed significantly positively correlated ( P & lt ; 0.001 ) fructose 2, 6 bisphosphate compared with fasting blood glucose. However, it besides shows non-significant relationship between diabetic and normal topics, while fructose 2, 6 bisphosphate showed significantly positively correlativity ( p & lt ; 0.001 ) with HbA1c. Figure-3 and 4 represents correlativity coefficient of fructose 2, 6 bisphosphate versus fasting blood sugar ( FBS ) and glycated haemoglobin ( HbA1c ) .
Comparison of age, tallness, weight and organic structure mass index of control with the diabetic topics.
The values are expressed as MeanA± S.E. The figure of observation and units are given in parenthesis.
Age ( Old ages )
Weight ( Kg )
Height ( m )
BMI ( kg/mA? )
44.90 A± 1.36
61.23 A± 1.54
63.87* A± 1.43
1.68* A± 1.33
27.63* A± 0.31
*P & lt ; 0.001 important when compared to command.
Comparison of fasting blood glucose, HbA1c and Fructose 2, 6 bisphosphate of control and diabetic topics.
The values are expressed as MeanA± S.E.M.
The figure of observation and units are given in parenthesis.
FBS ( mg/dl )
HbA1c ( % )
Fructose2,6 bisphosphate ( pmol )
86.54 A± 1.95
3.15 A± 0.11
137.70* A± 1.61
8.45* A± 0.11
6.91* A± 0.11
*P & lt ; 0.001 important when compared to command.
Co-efficient of correlativity ( R ) of Fructose 2, 6 bisphosphate ( pmol ) V FBS and HbA1c
FBS ( mg/dl )
R = -0.23
R = 0.15
R = 0.665*
HbA1c ( % )
R = 0.28
R = -0.05
R = 0.534*
* Correlation is important at the P & lt ; 0.001 degree
Figure # 1 Figure # 2
Correlation ( R ) of Fructose 2, 6 Correlation ( R ) of Fructose2,6
bisphosphate ( pmol ) V FBS bisphosphate ( pmol ) V HbA1c
Diabetess is a chronic upset that occurs when the pancreas does non bring forth adequate insulin or organic structure can non efficaciously use the insulin it produce.14 Infection tends to happen with greater frequence and badness in diabetic patients than in non-diabetics. A specific defect in innate and adaptative immune map was identified by many in vitro studies.15 Immune cells require glucose uptake and metamorphosis for normal map. High glucose degrees inhibit proliferation of peripheral mononucleate cells. Activated T cells have dramatically increased metabolic demand, glucose metamorphosis and aerophilic glycolysis due to fuel this demand.16
It was proposed decennaries ago that fasting glucose value is higher in diabetics.17 In our survey we measured fasting blood sugar to find the control of diabetes and measure the metabolic status and were in understanding of the above statement. Besides in our survey diabetic patients had higher fasting blood sugar values ( 137.70 A± 1.61mg/dl ) than control topics ( 86.54 A± 1.95mg/dl ) ( p & lt ; 0.001 ) as expected. Measurement of HbA1c provides a retrospective index of glycemic control over the 4 to 8 hebdomads before its finding helps diabetes direction and accommodation of therapy. In one study,15 it was found that high glycosylated Hb degrees are most likely to exhibit close association with peculiar infection and hyporesponsiveness. In another study,18 it was found significantly higher HbA1c in a group of 1480 topics with diabetic kidney disease. Atsume et al.,12 conducted an probe to see the consequence of long term hyperglycaemia on intracellular fructose 2,6 bisphosphate in immune cells, suggested that topics with higher HbA1c values have an addition intracellular fructose 2,6 bisphosphate in immune cells. Consequences of our survey besides showed important difference in HbA1c ( P & lt ; 0.001 ) in diabetics as compared to command existent values being 8.45 A± 0.10 and 4.33 A± 0.11 per cent severally. Immune cells activation requires an addition in glucose consumption and anaerobiotic glycolysis. Fructose 2,6 bisphosphate is a powerful activator of rate restricting enzyme of glycolysis, defects causes lessening in immune map in diabetic patients. Infection occur with increased frequence and badness in diabetes. Atsumi et al. , ( 2007 ) 12 showed intracellular fructose 2,6 bisphosphate degrees in peripheral blood mononuclear cells in diabetics and observed significantly higher than age matched control topics, our consequences besides showed positively important relationship between fructose 2,6 bisphosphate degrees and HbA1c ( r a•? 0.451, P & lt ; 0.001 ) . Consequences of Vander et al. , ( 2009 ) 6 indicated that activated thymocytes from diabetic rats showed two fold more fructose 2,6 bisphosphate than cells from normal rats, our survey besides in understanding of the above mentioned surveies with significantly high ( p & lt ; 0.001 ) degrees of fructose 2, 6 bisphosphate in immune cells of diabetics when compared with normal topics. We besides observed a important positive correlativity between intracellular fructose 2,6 bisphosphate degrees and long term glycemic control as assessed by HbA1c. These determination may assist to clear up the impaired map in immune cells in patients with diabetes.
It is concluded that in diabetes fructose 2,6 bisphosphate is increased in immune cells causes decreased in Numberss of immune cells which may bring on opportunity of infection.