Diabetes and periodontology

Introduction

Diabetes and periodontitis are two chronic conditions which have multifactorial aetiologies and many parameters to consider in order to bring about satisfactory long term treatment outcomes. Because of their progressive nature, regular maintenance therapy is necessary for both diseases.

In recent years, our concept of risk factors has modified our approach to the treatment of periodontitis. Smoking, which has long been known to be associated with cardiovascular diseases and lung cancer, is likewise a risk factor for periodontitis ^{(Haber, 1994)}. Similarly, diabetes and periodontal disease are linked, as shown by a whole series of studies, although some of them are contradictory. Nevertheless, the majority agree that diabetes is a risk factor that promotes the progression of periodontal disease. The reverse also seems to be true, that periodontal infection influences glycaemic control.

This review of the literature aims to recall the characteristics of diabetes and takes stock of the subject in order to evaluate the effect of diabetes on our treatments and thus the control of periodontal disease associated with this systemic condition.

Characteristics of diabetes

Sugar diabetes is a chronic disease characterized by one sign, hyperglycaemia, the permanent raising of the level of blood glucose. It is defined as a fasting blood glucose of > 1.26 g/l (7 mmol/l), after a minimum of 8 hours fast on two occasions ^{(Agence nationale d'accréditation et d'évaluation en santé, 1999)}.

The ^{American Diabetes Association (1997)} distinguishes :

- type 1 diabetes, previously « insulin dependent » ;

- type 2 diabetes, previously « non-insulin dependent » ;

- secondary diabetes, such as diabetes of pregnancy.

These are more rare, affecting approximately 5 % of diabetics.

Type 1 diabetes, which affects 10-15 % of diabetics, is characterised by an absolute deficiency of insulin, a tendency to acidosis, an acute onset before the age of 20, rarely later. It is due to a lymphocytic infiltration and a more or less complete (80-90 %) selective destruction of the b cells of the pancreas that are responsible for the secretion of insulin, by an auto-immune process. Insulin replacement therapy is essential in order to prevent acidosis and to assure survival. Type 2 diabetes represents approximately 85 % of cases. This is characterized by an inadequate secretion of insulin and a resistance of the peripheral tissues to the action of insulin. Its onset is insidious, usually over the age of 40 and the diagnosis is only made once several years have elapsed, because of good tolerance to a slight hyperglycaemia.

Treatment consists of regulating blood sugar levels by diet control or by hypoglycaemic drugs. One can temporarily resort to the use of insulin in order to regain control of blood sugar during an imbalance or if other hypoglycaemic agents fail. There is a hereditary element to the disease, combined with other factors related to life style and the environment, such as diet, a sedentary life style and raised stress levels.

Clinical signs and symptoms

These are a direct consequence of the hypoglycaemia and classically comprise the triad of polyuria, polydipsia and hunger, associated with fatigue and possibly weight loss. These features are found mostly in type 1 diabetes but equally, they may be found in type 2, to varying degrees. Nausea, associated with acidosis, may be noted in poorly controlled type 1 diabetes. These signs and symptoms may be reversed with early diagnosis and effective treatment.

Prevalence

Diabetes affects 2-10 % of the population, according to the country. It is classed amongst the 10 most common causes of death in Western countries ^{(Cutler et al., 1991)}. There are estimated to be 12 to 14 million diabetics in the United States. Over the next 15 years, they could double in number ^{(Miller et al., 1992} ; ^{American Academy of Periondotology, 1999)}. These predictions are due to modern dietary habits and a more and more sedentary lifestyle. In France, there are 2 million diabetic individuals, to whom should be added a further 500,000 approximately, who are undiagnosed.

In consequence, it is highly probable that the dental surgeon will be called upon to treat more and more diabetic patients.

Evaluation of blood sugar

Without insulin, or if the insulin present is ineffective, the passage of glucose through the cell membrane is inadequate and as a consequence there is an accumulation of glucose in the blood, or hyperglycaemia. The blood sugar estimations usually used are the fasting glucose level or the haemoglobin glucose level.

Fasting blood sugar (plasma glucose level)

This is expressed in mmol/l (previously in g/l). The relationship between these two entities is : mmol/l = g/l X 5.5. The normal value varies from 0.8 to 1.26 g/l, which is 4.4 to 6.93 mmol/l.

Haemoglobin glucose

Glucose is irreversibly fixed to haemoglobin, so that its level depends on the level of blood sugar and on the half life of the blood corpuscle, which is 6-8 weeks. It is expressed as a percentage. The normal value is 4.5-5.7 %. Fasting blood sugar gives the level of blood glucose at a given time and is therefore of limited value. The haemoglobin glucose reflects the long term mean blood glucose level over a 2 month period (the half life of the red blood corpuscle). In fact, this non-instantaneous assessment is of major importance in the maintenance of diabetic patients and the control of their metabolism. Its advantage in comparison with fasting blood glucose is to provide a greater precision of diagnosis and to enable calculation dosages without the patient having to fast.

Complications of diabetes

Progress in the surveillance and the treatment of diabetes has increased the life expectancy of diabetics. However, this allows the development of degenerative complications of the disease in type 1 as well as type 2 diabetics, which today are the major problem. Hyperglycaemia, rarely perfectly controlled in the long term, often brings with it metabolic and physiological changes which give rise to complications involving the blood vessels (at both microscopic and macroscopic levels) as well as delayed healing. The microscopic complications are linked to a diffuse microangiopathy affecting the capillaries.

Chronic hyperglycaemia leads to glycosylation and a thickening of the of the basal membranes of the capillaries which affect the retina, kidneys and also other tissues, the outcome of which is to cause retinopathy, nephropathy or neuropathy, the latter consisting of a progressive lesion of the peripheral nerves. Retinopathy is often asymptomatic, may not be detected and can progress rapidly to blindness. This is the most common complication and, in general, the first to appear.

Macroangiopathy is a complication of diabetes that is more common in subjects of European origin. Classically it causes arterial hypertension, reduced coronary blood flow, cerebro-vascular pathologies and arteritis involving the lower extremities with the risk of ulceration and gangrene of the feet. As far as the effects on healing are concerned, they are due directly to the diabetic changes involving the vasculature, as well as to collagen metabolism. Details of this will follow later.

Oral manifestations of diabetes frequently comprise dry mouth, a burning sensation of the tongue, xerostomia, an increase in candidal infections, oral paraesthesia, glossodynia and a reduction in taste sensation ^{(Rose et al., 1995)}. The last three features are related to neuropathy, one of the major complications of diabetes. According to ^Gautier , mucosal lesions such as angular cheilitis and aphthous ulceration are frequent. The complications observed in diabetics seem to be associated with the duration of the disease and its poor metabolic control. They are, however, not inevitable. In contrast, there are diabetics who are well controlled but who develop complications only a few years after the beginning of their illness. Genetic factors could be the cause of these individual variations.

Periodontal complications of diabetes

In view of the fact that many studies have shown that periodontal disease occurs more frequently and is more severe in diabetics, it has recently been considered to be the sixth complication of diabetes ^{(Loë, 1993)}. If the results seem a little equivocal for type 2 diabetes, those for type 1 are less homogenous and clear cut than one would expect from the undoubted links between the different parameters of these two diseases.

Type 1 diabetes

Nevertheless, one finds a general consensus in the literature that the prevalence of periodontitis is increased in patients with type 1 diabetes even if, according to the authors, results are variable according to the different parameters being studied. ^Cianciola , in a study of 263 diabetic patients, observed an overall prevalence of periodontitis of 9.8 %, which was significantly higher than in the control group. In children of 11 to 18 years of age, the prevalence is 1.7 % and increases with age. By the age of 19 to 32 years 39 % suffer from periodontitis, whilst the prevalence in the control group is 2.5 %.

In children, although many authors have shown there to be more gingival inflammation in diabetics (^{Novaes et al., 1991} ; de ^{Pommereau et al., 1992}), an increased prevalence of periodontitis has been found only in the study by ^Cianciola . It is necessary, therefore, to treat these results with caution, taking into account the absence of precise knowledge on the state of balance of the diabetes as well as the ethnicity of the subjects.

^Bacic and ^Hugoson observed more 6 mm pockets, bone loss and missing teeth in a population of type 1 diabetics compared with a control group. An association between periodontitis and other complications of diabetes has been demonstrated ^{(Bacic et al., 1988)}. ^{Safkan-Seppälä and Ainamo (1992)}, in a study of 71 type 1 diabetics with a mean duration of disease of 16.5 years, made a distinction between subjects who were well controlled and poorly controlled. With similar standards of plaque control, the poorly controlled patients suffered greater loss of attachment and bone loss around some teeth compared with the well controlled diabetics. ^Moore , in a two year study of 320 patients with type 1 diabetes, showed evidence of greater loss of attachment in older patients even when bleeding on probing and the amounts of calculus were similar. According to these authors there is a direct correlation between the severity of periodontitis, early onset of diabetes (about 8 years) and age. Both of the latter factors were evidently linked to the duration of the disease.

Other authors have not found a connection between type 1 diabetes and periodontitis (^{Taylor et al., 1998} ; ^{Sbordone et al., 1998)} but it seems that in most of these studies the patients were young and therefore had not been exposed to the disease for a long period of time.

Type 2 diabetes

Evidence of a correlation between diabetes and periodontitis is more marked when one examines the results of studies on type 2 diabetes. Epidemiological studies have been carried out on Pimas Indians, a population that suffers an extremely high prevalence of type 2 diabetes (approximately 40 %). In an initial study of 3,219 subjects belonging to this community, the diabetics had a greater prevalence of periodontal disease in respect of loss of attachment and bone loss, compared with the non-diabetics, suggesting that diabetes is a risk factor for periodontal disease ^{(Shlossman et al., 1990)}. The studies of ^Emrich , > ^Nelson and ^Taylor show similar results. ^Emrich , in a study of 1,342 individuals, concluded that diabetic subjects are three times more at risk of developing periodontal disease compared with non-diabetics. Similarly, ^Nelson demonstrated that the prevalence periodontal disease in diabetics is 60 %, whereas in non-diabetics it is 36 %. ^Taylor , in a two-year study, showed evidence that there is a 4.2 times higher risk of progressive alveolar bone loss in diabetics compared with non-diabetics.

Therefore, the great majority of studies seem to show a relationship between diabetes and periodontal disease, especially in patients whose tissues have been exposed to hyperglycaemia over a long period of time, with poor metabolic control of the diabetes and thus the presence of other serious complications.

These findings allow ^{Loë (1993)} to affirm that periodontitis is well and truly the sixth complication of diabetes. ^{Papapanou and Lindhe (1997)} maintain a distinction between a potential risk factor and a true risk factor. For example, smoking and diabetes seem to be true risk factors for the development of periodontal disease, whereas stress and osteoporosis seem to be potential risk factors and the resulting susceptibility seems not to be correlated to the levels of plaque and calculus ^{(Seppälä et al., 1993)}.

Mechanisms of action of diabetes on periodontal health

Although not all the mechanisms of the pathogenesis of these diseases have been elucidated, various studies over the last few years have increased our understanding.

Vascular theory

One of the first effects of prolonged hyperglycaemia is microangiopathy. The excess sugar in the blood reacts with plasma proteins and causes the accumulation of glycosylation products known as AGE (advanced glycosylation endproducts) on the walls of blood vessels. The vessel walls become thickened and their permeability is affected. This will interfere with the passage of defence cells to the sites of disease, reduce metabolic exchange between the blood and tissues and interfere with the transport of oxygen to the tissues. If one adds to this the reduced efficiency of the glycosylated haemoglobin, one can see that there will be a rapid under-oxygenation of the tissues.

More recently, it has also been demonstrated that inflammatory cells react specifically with AGE, liberating cytokines which maintain the inflammatory process. Also, endothelial cells react with AGE (advanced glycation endproducts), liberating a powerful vasoconstrictor that could be the cause of local necrosis. According to ^Grossi , the diabetic complications that occur in the other organs have the same pathogenesis and are therefore directly associated with the hyperglycaemia.

Immunity theory

The diabetic patient presents with a dysfunction of the polymorphonuclear leucocytes (PMNs) which involves reduced chemotaxis, reduced adherence to vessel walls and also of phagocytosis. ^Cutler have noted reduced chemotaxis of PMNs to Porphyromonas gingivalis, one of the major pathogenic microorganism implicated in periodontal diseases. The origins of this defect have yet to be determined. It should be stressed, however, that not all diabetics present with PMN defects and periodontal disease. According to ^Ainamo , it seems that only those patients with PMNs exhibiting defective chemotaxis develop an unusual severity of periodontitis.

Collagen theory

Collagen metabolism is upset by hyperglycaemia and this brings about a reduction in the production of bone matrix by osteoblasts, reduced synthesis of collagen by fibroblasts and an increase in collagen breakdown. The increase in the breakdown of collagen in the gingival tissues of diabetics could explain the rapid periodontal breakdown that is observed in some patients. These disturbances could be produced in vitro and in germ free animal studies, which clearly demonstrates that hyperglycaemia is the cause. Furthermore, it has also been shown that diabetes accelerates the degradation of collagen fibres in the process of synthesis and therefore has a negative effect on healing. Other possible mechanisms could be genetic ^{(Rotler et al., 1990} ; ^{Katz et al., 1987)} and hormonal ^{(Zachariasen, 1991)}.

The effect of periodontal treatment on the metabolic control of diabets

There are several studies that demonstrate that acute infection is brought about by insulin resistance. ^Drobny studied the insulin receptors in 7 subjects during moderately severe bacterial and viral infections. They concluded that a resistance to insulin is directly linked to a lack of receptors on the surface of macrophages. ^{Sammalkorpi (1989)} measured glucose tolerance during infection and convalescence in subjects with bacterial or viral infections. Insulin increases and glucagon decreases during and after infections. The index of resistance to insulin (glucose X insulin) increased by 33 % during infection and exceeded 28 % during convalescence. This resistance is not correlated with either the severity of infection or the infecting agent. It is more pronounced in younger subjects than in older ones. Furthermore, there is a long period after the infection has been eliminated before the situation returns to the initial state. ^Yki-Jarvinen studied the severity, the duration and the mechanisms of resistance to insulin in 8 patients during an acute infection and then 1 and 3 months later. According to them, the mechanism seemed to be the result of a diminution of glycogenolysis giving rise to a long-lasting effect on the action of insulin. Therefore, the cellular and molecular interactions caused by the inflammation would have an influence on glycosylation and, indirectly, on the metabolic control of the diabetes but few studies have been published on this subject. ^{Williams and Mahan (1960)} made the first observations to establish the effects of periodontal infections. Similarly, ^{Wolf (1977)} showed that insulin-dependent diabetics, having responded positively to periodontal therapy, experienced an improvement in their diabetic control, a reduction in glycosuria, hyperglycaemia and in the dose of insulin necessary, whereas those subjects who did not respond well to periodontal therapy, did not experience any change in their diabetic control. ^Seppälä undertook a longitudinal study of the effects of periodontal therapy on the metabolic control of their insulin-dependent diabetic patients. The 66 patients were divided into two groups, 48 of whom had poor metabolic control and 18 more favourable. At the end of 1 year they noted a reduction in glycosylated haemoglobin (HbA1c) in both groups. After 2 years, the reduction in the group with poor metabolic control was not significant (p < 0.068), whereas it was in the other group. Studies by ^Aldridge and ^Smith did not show an improvement in the metabolic control of diabetes after periodontal treatment.

^Miller , in the course of a pilot study on 9 subjects suffering from type 2 diabetes and having received non-surgical periodontal therapy, observed that the 5 patients experiencing a reduction of bleeding on probing showed better control of blood sugar, compared with the remainder whose periodontal condition had not been brought under control. The authors concluded that an improvement of periodontal health may be accompanied by better metabolic control of the diabetes.

In the study by ^Grossi , 113 subjects suffering from type 2 diabetes were divided into 5 groups according to the type of initial therapy they received for their periodontal disease. The groups taking systemic doxycycline experienced a reduction in HbA1c of 10 % compared with their initial value. It must, however, be stated that the level of HbA1c increased slightly again between 3 and 6 months. This could correspond to a return of the pathogenic flora that had not been entirely eradicated. The long term ability to control and eradicate the sources of periodontal infection would be a major factor, without which metabolic control of the diabetes would not have been affected. ^Christgau , who combined type 1 and type 2 diabetes, did not find a significant improvement in metabolic control of the diabetes after resolving the periodontal condition, although this group of patients were relatively well controlled at the beginning.

The effect of diabetes on the response to periodontal treatment

It has been well established that diabetes is a risk factor for periodontal disease ^{(Oliver and Tervonen, 1994)}. Furthermore, several studies have shown that diabetes can affect the efficacy of our treatments in the more or less long term in patients exposed to long periods of hyperglycaemia, as in poorly controlled diabetes. ^Bay , ^Sastrowijoto , ^Tervonen and ^Christgau did not observe any short term differences after non-surgical treatment between diabetics and non-diabetics. ^Westfelt studied the rate of periodontal disease recurrence after 5 years in diabetics, compared with non-diabetics and concluded that those patients in both groups who, after surgery, maintained a meticulous programme of maintenance, experienced a very low rate of recurrence. ^Grossi showed the importance of eradicating Porphyromonas gingivalis using systemic antibiotics (doxycycline) in order to prevent recurrence. However, ^{Tervonen and Karjalainen (1997)} consider that it is the quality of metabolic control is the most important factor and that recurrence of the periodontal disease correlates with the control of blood sugar and diabetic complications.

Discussion

Frequently, results of studies on the effects of periodontal treatment on the metabolic control of diabetes cannot be applied to all cases. They vary according to the type of diabetes, its clinical characteristics, the presence or absence of control subjects, or the periodontal therapy proposed. Whilst ^{Williams and Mahan (1960)}, ^{Wolf (1977)} and ^Miller observed that eradication of the source of periodontal infection could assist the control of diabetes, ^Smith , ^Aldridge and ^Christgau did not produce evidence to show that periodontal treatment influenced blood sugar control. The duration of their studies seemed to be somewhat short to enable detection of any long term change in this control, which could explain these discrepancies. Further work taking into account the characteristics of both the diabetes and the periodontitis are needed in order to define this influence more clearly. As far as the effect of diabetes on the response to periodontal treatment is concerned, the results of studies appear to be equally contradictory.

^Bay , ^Sastrowijoto , ^Tervonen , ^Westfelt and ^Christgau did not find any significant difference in the response to periodontal therapy in diabetic and non-diabetic patients. The length of the study was often too short (1 week to 6 months post therapy), as well as the unequal evaluation of the long term characteristics of the diabetes from which one could draw convincing conclusions. ^Westfelt had well-researched data on the various characteristics of diabetes, their observations extended over a long period (5 years) and the subjects underwent a rigorous periodontal maintenance programme every 3 months during this period. ^Christgau only presented 1 subject with a level of glycosylated haemoglobin > 10 %. In addition, the general complications of diabetes were not evaluated. The study by ^Grossi did not have a control group and they were only interested in evaluating the efficacy of one therapy, in this case the use of tetracyclines, for their anti-bacterial properties and modification of host response. The sample, 85 Pima Indians, was large and homogenous, nevertheless a long term study would be needed to assess any recurrence of the periodontal disease. In addition, the use of tetracyclines seems to have a beneficial effect on the immunological and metabolic changes that occur due to periodontitis in diabetic patients. Only ^{Tervonen and Karjalainen (1997)} found a difference in the response to periodontal therapy in diabetics compared with non-diabetics. Their study is the only one that, in a large test group, takes into account the characteristics of diabetes in relation to prolonged hyperglycaemia (control of disease, presence of one or more complications). They have demonstrated the difficulty of controlling periodontal disease after non-surgical therapy in diabetic patients whose hyperglycaemia, in terms of level and duration, are elevated and whose standards of oral hygiene are comparable. These results seem to corroborate their 1993 observations ^{(Tervonen and Oliver, 1993)} where they stated that each episode of impaired metabolic control could aggravate pre-existing periodontal damage because rapid progression of periodontitis seems to be associated with hyperglycaemia ^{(Ainamo et al., 1990)}.

Therefore, when faced with periodontitis that persistently responds poorly to conventional therapy, blood sugar estimations should be performed in order to differentiate between diabetes-associated periodontitis and refractory periodontitis.

Conclusion

Prolonged hyperglycaemia is known to bring about systemic complications such as retinopathy, nephropathology, neuropathy or cardio-vascular disease. The severity of such a clinical scenario causes significant mortality, is often associated with advanced periodontitis ^{(Karjalainen et al., 1994)}, and is considered to be the sixth complication of diabetes ^{(Loë, 1993)}.

The mechanism of action of diabetes on blood vessels, immunity and collagen, is linked to hyperglycaemia. This, in a patient with a genetic predisposition, is the origin of periodontal complications. When diabetes is poorly controlled over a long period of time and/or involves several complications, the periodontal disease, which is often present, seems to respond poorly to treatment and is more prone to relapse, compared with a well-controlled diabetic and, especially, with a non-diabetic ^{(Tervonen and Karjalainen, 1997)}.

Therefore, taking into account the large number of undiagnosed diabetics (estimated to be 500,000 in France), such periodontitis, which one could easily label as refractory, should not be classified as such once the diabetic risk has been identified ^{(Kornman, 1996)}.

The progression of systemic and periodontal complications linked to diabetes seems to slow down when the disease is very well controlled ^{(American Academy of Periodontology, 1999)}. Equally, periodontal infection could affect the metabolic control of the diabetes.

Cooperation between the endocrinologist and the periodontist is therefore essential. In order to provide adequate oral care, the dentist must be alert to the diabetic state of each patient. Information on the long term glycosylated haemoglobin levels and the presence or absence of diabetic complications are necessary to evaluate the periodontal prognosis and to modify the treatment accordingly. It is equally important that the endocrinologist is informed of the presence of sites of periodontal infection in the patient ^{(Tervonen and Karjalainen, 1997)}.

Nevertheless, further studies are necessary to evaluate :

- more precisely the effect of elimination of periodontal infection on diabetic control ;

- the long term effects of periodontal treatment, especially surgical, in severe cases of diabetes.

Demande de tirés à part

Michel Uzan, 20, rue Caulaincourt, 75018 PARIS, FRANCE.

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