Fasting hyperglycemia and postprandial: an aid to a more targeted prognosis.

A state of persistent hyperglycaemia continued over time acts in concert with other cardiovascular risk factors within or in the context of the metabolic syndrome * , to cause vascular damage .

Patients with hyperglycemia often have:

insulin resistance and hyperinsulinemia;
increased blood pressure;
increased triglycerides, increased LDL and low HDL cholesterol levels;
central obesity, high levels of inhibitors of plasminogen activator and low-grade inflammation .

Nevertheless, experimental models confirm the importance of the direct effect of even slight alterations of glucose homeostasis in the atherosclerotic process .

* More on the Metabolic Syndrome

What is metabolic syndrome ?
The term “metabolic syndrome” identifies a set of metabolic risk factors that increase the chance of developing heart disease , stroke and diabetes , the precise cause of the metabolic syndrome is not known although there are many evidences that some genetic factors , the presence of a excessive amount of body fat , especially in the abdomen , and lack of exercise contribute to the development of this condition.

Metabolic syndrome is diagnosed when three or more of the following risk factors:
high amount of abdominal adipose tissue (assessed by measuring waist circumference ) are considered pathological values ​​greater than 94 cm in ‘man and greater than 80 cm in women) ;
low HDL cholesterol ( the so-called “good cholesterol” ) : less than 40 mg / dl in men and less than 50 mg / dL in women) ;
high triglyceride levels : values ​​greater than 150 mg / dL ;
high blood pressure : greater than 135/85 mmHg or if it is already in an anti-hypertensive therapy ) ; elevated glucose levels : fasting blood glucose greater than 100 mg / dL.

The presence of three or more of these risk factors is a sign that the organism is resistant to the action of ‘ insulin, a hormone produced by the pancreas important : in these cases, ie when there is a condition of insulin resistance is required a greater amount of insulin than normal to maintain normal blood sugar levels.

The finding of high levels of insulin in the blood compared with normal glycemia levels is an indirect indicator of the condition.

Who runs the risk of developing metabolic syndrome ?
The metabolic syndrome is very common in the population, and the risk of developing the syndrome increases with age.
A person can be considered at risk for developing the metabolic syndrome if you do not exercise and if : is increased in weight , especially at the level of waist circumference ( this simple measurement is an index of excessive expansion of visceral adipose tissue , that is, which is located inside the abdomen and surrounding the viscera ) ;
has a history of diabetes ;
has high levels of triglycerides in the blood ;
has high blood pressure .

Most of the people who have the metabolic syndrome feels good and often have no symptoms , but these people have a higher risk of developing serious diseases in the future such as diabetes and cardiovascular disease , especially in the presence of family history , and should immediately change their eating habits .

The first alterations in glucose homeostasis often reveal themselves as post-prandial hyperglycaemia .

The persistent and systematic increases in blood glucose levels post- prandial glycemic contribute significantly to the overall exposure of body tissues : in addition, the excessive and repeated glucose excursions lead to increased glycemic variability .

Today , we know that the exposure glucose and glucose variability contribute to the development of atherosclerosis : the arterial wall , in fact , is a critical target for these insults glucose .
The glycosylation of proteins ( caused by the presence of elevated glucose levels that persisted in the body end up reacting with the -NH2 groups of the residues of proteins) due crosslinks with collagen and other extracellular matrix proteins in the arterial wall , and increasing favoring the formation of atherosclerotic processes .

Glycosylation of LDL particles ( caused by the presence of elevated glucose levels that persisted in the body end to react with LDL oxidization, stimulates the activation of macrophages, and the formation of foam cells first mover for the formation of the atheromatous plaque.

Even more direct action is exerted by the glucose molecules in long stay in the bloodstream that react with the NH2 – terminal of the endothelial cells , causing endothelial dysfunction , an early manifestation of atherosclerosis, and an important prognostic factor for cardiovascular disease .

In type 2 diabetes , blood sugar fluctuations during the post prandial or, more generally , all the extreme fluctuations seem to have a more specific triggering effect on oxidative stress than chronic hyperglycemia : In vitro studies have demonstrated increased expression of markers of oxidative stress in cells exposed to fluctuating concentrations of glucose.

The hyperglycemia in non-insulin- dependent tissues , such as endothelial cells , causes a super production of free radicals and superoxide by the mitochondrial respiratory chain ; free radicals may mediate some of the effects associated with hyperglycemia such as vasoconstriction , activation of the coagulation , increased expression of adhesion molecules , etc. .

The post-prandial hyperglycemia and glucose variability are also associated with an inflammatory state reported by the formation of advanced glycosylation products (AGE ‘s) , with a marked increase in the levels of C-reactive protein and TNF -a.

Acute hyperglycaemia activates the formation of carbonyls , leading to the formation of highly reactive species such as methylglyoxal or 3 – deossiglucusone .Borderline hyperglycemia and cardiovascular complications For many years the categories of hyperglycemia borderline impaired glucose tolerance (IGT) and fasting hyperglycemia (IFG ) were considered only as risk factors for the development of diabetes, with minimal or negligible effects on micro- and macrovascular complications .

The systematic review of the data in different databases however, shows that the correlation between glycemia and cardiovascular risk starts from the normal range of plasma glucose concentrations with a linear relationship that does not show a threshold effect .
Both IGT and IFG are well correlated with cardiovascular risk : in fact, both categories are correlated independently with cardiovascular risk.
In an attempt to evaluate the influence of the two separate components, other authors , after adjustment for other risk factors , reported that postprandial blood glucose shows a stronger correlation with cardiovascular disease than fasting glucose .

Another way to study the correlations between borderline dysglycemia and cardiovascular disease is to follow prospectively patients with isolated fasting hyperglycemia (IFG ) and isolated postprandial hyperglycemia (IGT) and follow them over time to assess how these variables affect the time the risk of cardiovascular disease.
The study group Funagata has observed a higher cardiovascular mortality in subjects with IGT than those with IFG ; these results were confirmed later by other authors.

Considering the literature data together , it is therefore possible to say that the IGT evaluated with load curve shows a good correlation with the postprandial blood glucose and can be considered a surrogate for postprandial glycemia .
In addition, the correlation between blood glucose measured by the load curve and cardiovascular disease is independent of fasting glucose or glycosylated hemoglobin .

These observations can be interpreted in several ways: firstly, it is possible that hyperglycemia contributes more than the fasting glucose glycemic overall exposure in the early stages of diabetes.
That does not explain , however , why,postprandial blood glucose has an effect independent of glycosylated hemoglobin .

Another explanation is that the IGT correlates better with the cardiovascular risk in consequence of the higher prevalence of the metabolic syndrome in this population , which itself significantly increases the risk of cardiovascular events .
This hypothesis contradicts , however , that previous studies had shown that the effect of postprandial blood glucose is independent of other cardiovascular risk factors .

Finally, it is possible that the postprandial blood glucose is associated with higher blood sugar levels during the day and that this have a detrimental effect more pronounced on the vessels and on cardiac function ( oxidative stress , abnormal vascular motility , abnormal blood flow , etc. . ) compared to the glycemic status during fasting .

Differences between the postprandial glycemic peaks during periods of fasting and those may result in different levels of cardiovascular risk in these subjects.

Numerous studies have shown that microvascular and macrovascular complications are mainly or partially dependent disglicemia which has two components: persistent chronic hyperglycemia and acute glucose fluctuations from peak to nadir .

Both components leading to diabetic complications through two main mechanisms: excessive protein glycosylation and activation of oxidative stress .
Several years ago, these two mechanisms were unified in a very elegant theory , which suggested that the riots glucose observed in diabetic patients were the result from the activation of oxidative stress causing excessive production of superoxide by the mitochondrial respiratory chain delegated to the transfer of electrons.

This activation in turn produced a cascade of metabolic events characterized by increased activity of polyols , increased production of advanced glycosylation products , activation of protein kinase C and nuclear factor NF- kB, increased synthesis of Examining .

Today, most of the scholars of both the diabetes but also metabolic diseases agrees to judge the disglicemia a factor not to be overlooked at all.

Common sense suggests to us as a clinical control of both fasting blood glucose but most of the postprandial glucose as well as the activation of CRP and glycated hemoglobin should be monitored even in non-diabetic patients even with clear elements of metabolic syndrome in place.


The image is a watercolor by BRUNA MILANI



1 . BONORA , E. CALATERRA , F. and Coll . : Plasma glucose levels Throughout the day and Hb A1c interrelationship in type 2 diabetes . Implications for treatment and monitoring of metabolic control. Diabetes Care : 2002,24.2023-9

2 . HENEFELD , M. and Coll . : Postprandial glucose is an independent risk factor for Increased carotid intima- media thickness in non- diabetic individuals Atherosclerosis . , 1999, 144:229

3 . KUIZON , D. and Coll . : Glucose tolerance and cardiovascular mortality : comparison of fasting and 2- hour diagnostic criteria . Arch.Intern.Med . , 2001, 161:397

4 . Luzi , L. and DE Fronzo , RA : Effect of loss of first phase insulin secretion on hepatic glucose production and tissue glucose disposal in humans . Am J.Physiol . 1989 257:704

5 . PARTLEY , R.E. and Coll . : The role of impaired early insulin secretion in the pathogenesis of type 2 diabetes mellitus . Diabetologia . , 2002, 44:929

6 . Polonsky , KS et al. : Abnormal patterns of insulin secretion in non- insulin dependent diabetes mellitus . N.Engl.J.Med . : 318 , 1231-39 , 1988

7 . Reaven GM : The fourth musketeer – from Alexander Dumas to Claude Bernard . Diabetologia : 38, 3-13 , 1995.

8.TURNER , R.C. and Coll . : Glycemia control with diet , sulfonyurea , metformin or insulin in patients with type 2 diabetes mellitus : progressive requirement for multiple therapies (UKPDS 49) JAMA , 1999: 281 , 2005-12.