T1DM, formerly referred to as insulin-dependent DM, constitutes approximately 3–5% of all cases of DM and is related to autoimmune-mediated destruction of the insulin-producing β cells of the islets of Langerhans in the pancreas. The absolute lack of insulin means that individuals with T1DM cannot utilize glucose in the blood, hyperglycemia results, and affected individuals utilize other energy sources. In general, the major classic findings of hyperglycemia with polyuria, polydipsia, polyphagia, weight loss, and fatigue occur in the setting of new-onset diabetes in young individuals whose disease is caused by profound insulin deficiency [7]. When fats and proteins are metabolized, the production of ketones is a by-product, which ultimately results in ketoacidosis, an acute and potentially life-threatening metabolic complication. Ketoacidosis may develop rapidly and lower the pH of the blood, leading to coma and death. The onset of signs and symptoms of DM in these individuals is relatively abrupt and usually occurs at a young age (mean of 15 years), although T1DM may occur at any age. The destruction of the β cells in T1DM has been linked to the presence of certain major histocompatibility locus antigens (HLA), some of which are also associated with other autoimmune diseases [7]. More than 60 genetic loci have been identified that increase the risk of developing T1DM. At present, however, this complex situation does not offer information to aid in management of patients with T1DM [8].

T2DM accounts for approximately 95% of all cases of the disease. The serum blood glucose level is elevated, but the insulin levels of affected individuals may be normal, increased, or decreased. There is no profound insulin deficiency. However, over many years, the majority of individuals with T2DM have shown a continual decrease in their insulin levels. The etiology and pathogenesis of T2DM is heterogeneous due to a complex interplay of lifestyle factors and genetic predisposition [7]. Lifestyle factors include diet, lack of physical activity, and obesity.

The hyperglycemia in T2DM is not caused by autoimmune destruction of β-cells; rather it is due to inadequate insulin production in the context of insulin resistance. These individuals are not generally prone to ketoacidosis and may not be dependent on exogenous insulin to sustain life. However, insulin treatment for people with T2DM (25–30% of cases) can improve glycemic control.

Obesity is a very important risk factor for, and is frequently associated with T2DM [9]. There is a close association between the increase in obesity in the United States and the increased prevalence of T2DM. Obesity increases insulin levels and decreases the concentration of insulin receptors and their sensitivity in tissue, including skeletal muscle and fat. Exercise increases the number of insulin receptors and improves insulin sensitivity, whereas a sedentary lifestyle is associated with glucose intolerance. Regular exercise with weight loss is associated with a decreased incidence of T2DM after adjusting for body mass index (BMI) [7].

There is a strong familial component in T2DM. However, a family history is not an absolute prerequisite for the development of the disease, as some patients develop DM without any known family history. Sixty percent of patients with T2DM have either a parent or a sibling with the disease. T2DM is a complex disease, with multiple risk factors. An evaluation of the risk for T2DM in both monozygotic and dizygotic twins indicated that the coincidence was similar (monozygotic = 0.76, dizygotic = 0.71). The authors concluded that being a twin is associated with an increased risk, but that the fetal environment is of greater significance than genetic determinants of the disease [10]. Despite the high familial prevalence of T2DM, the precise mode of inheritance remains undefined. As also noted for T1DM, a large number of genes have been associated with increased risk of T2DM. The attributable risk for all of these loci is quite low, so genetic testing is not now useful in assessing a person’s risk of developing the disease.

Elevated levels of blood glucose are a recognized complication of pregnancy. This tends to develop in the second trimester, and is seen in 5–10% of women who have not had a previous diagnosis of DM [11]. The underlying mechanism is a lack of receptor responsiveness to insulin. The cause is unknown, but may relate to the effects of pregnancy hormones. Risk factors for gestational diabetes include previous dysglycemia, increasing age, race (African–American), being overweight/obese, and a previous pregnancy with a baby born with a birth weight of more than 9 lbs. Gestational diabetes is not generally associated with any symptoms, and is usually detected as part of a prenatal screening for the disease when women are 24–28 weeks pregnant. Following an 8 hour fast, an oral glucose tolerance test is typically done with subsequent blood glucose measurements 1 and 2 hours postprandially after drinking a 75gram glucose solution. A fasting blood glucose of 92 mg/dL or greater or a 1 hour postprandial glucose of 180 mg/dL or greater, or a 2 hour postprandial glucose of 153 mg/dL or greater is diagnostic of the disease [58].

The goal of treatment of gestational diabetes is to reduce fetal and maternal complications. Reducing the glucose level in blood can be achieved in a number of ways, including reducing the risk by counseling prior to becoming pregnant (diet and lifestyle changes). The same approaches are the basis of management if a diagnosis of gestational diabetes is made [12]. Diet management is particularly important during pregnancy (see Chapter 2), and should be overseen by the patient’s physician and an RD. Diet management approaches are addressed in Table 11.6 and Sections “Co-Morbidities and Diabetes” and “Nutrition and Diet Management of Diabetes” of this chapter. If diet and lifestyle changes are not sufficient, medication may be required. Insulin is often utilized.

An association of gestational diabetes and periodontitis has been proposed [13]. Women who were pregnant and had gestational diabetes were compared to a group of women who were pregnant but did not have gestational diabetes. Based on the established definition of periodontal disease, 77% of women with gestational diabetes also had periodontitis, versus 58% for pregnant women without gestational diabetes. Using logistic regression analysis, and controlling for many potentially important variables such as BMI, smoking, and family history of diabetes, the adjusted odds ratio was 2.6 (95% CI 1.1–6.1).

A case–control study of women with gestational diabetes and a group of pregnant women without DM examined clinical parameters and serum markers of inflammation [14]. Using their definition of periodontitis, half of the women with gestational diabetes had periodontitis, versus approximately half that percentage if gestational diabetes was not present (odds ratio = 3.0, 95% CI = 1.2–7.6). The women with gestational diabetes also demonstrated significantly higher blood levels of C-reactive protein. Using a fully adjusted logistic model that accounted for variables such as BMI and the amount of weight that was gained during pregnancy, the association between periodontitis and gestational diabetes remained significant.

The fourth type of DM is referred to as “other,” and includes a large number of generally uncommon entities such as those associated with a specific genetic basis, disorders of the pancreas (i.e., related to cystic fibrosis, or traumatic damage to the pancreas), endocrine disorders (i.e., Cushing syndrome), drug-induced diabetes (i.e., glucocorticoid usage), and diabetes resulting from infections of the pancreas (i.e., cytomegalovirus).

Periodontal disease is a common oral manifestation of DM [6]. Furthermore, there is evidence that periodontal disease can adversely affect metabolic control in patients with DM. This bidirectional relationship has led to increased focus on the relationship of these two common, chronic disorders.

The fact that periodontitis is more severe in patients with DM is now established [16, 17]. The evidence suggests that this risk is approximately threefold [18]. The majority of these studies have been conducted in patients with T2DM, as both DM and periodontal disease are more common as individuals reach middle age and old age. As the duration of DM increases, so does the severity of periodontal disease [19]. Periodontal changes also occur in younger patients with T1DM [20, 21]. These findings have led to call for periodontal disease to be the “sixth clinical complication of diabetes” [22].

The pathophysiology of increased severity of periodontal disease in patients with DM is believed to be due to an enhanced inflammatory response. One important mechanism is the increased deposition of advanced glycation end-products (AGE; formed via a multi-step, non-enzymatic reaction between reducing sugar such as glucose and proteins). AGE binds to specific receptors (RAGE) found on a variety of cells, including macrophages and endothelial cells [23]. This receptor-ligand binding results in the increased production of proinflammatory mediators, including IL-6 and TNF-α. Oxidative stress also increases, and production of reactive oxygen species and release of degradative enzymes establishes a local environment that could promote damage to endothelial cells and degradation of non-mineralized and mineralized connective tissue.

Other host-specific changes that may account for the increased prevalence of periodontitis in patients with DM include abnormalities of polymorphonuclear leukocyte (PMN) function; both decreased chemotaxis [24] and an enhanced respiratory burst have been reported [25]. PMN migrate in large numbers into the gingival crevice and when present release proinflammatory mediators (cytokines and catabolic enzymes) that can cause tissue damage. Further, there may also be reduced local repair capacity in the periodontal tissues. Infection with Porphyromonas gingivalis in mice that were diabetic demonstrated greater fibroblast apoptosis and reduced repair capacity [26].

Periodontal inflammation is driven by the presence of specific microorganisms in the subgingival environment. Periodontal pathogens such as A. actinomycetemcomitans, P. gingivalis, and P. intermedia have been shown to be important in periodontitis in the absence of the modifying effects of DM. Studies of the microflora in periodontitis in patients with DM have not identified any major differences in the microflora of patients with periodontitis who are not affected by DM [27].

The bidirectional relationship between periodontitis and DM is of major importance to all healthcare professionals who treat individuals with DM. Infection in patients with DM is recognized to result in adverse changes in metabolic control [28]. Subsequently, studies have found that periodontal therapy can improve glycemic control in patients with DM, and several meta-analyses have concluded that conservative periodontal therapy in patients with DM and periodontitis resulted in a decrease in HbA1c of 0.4% over a period of at least 3 months [29, 30].

Several population studies have suggested that periodontitis may be a risk factor for increased morbidity and mortality associated with DM. The Gila River Native American community has been extensively studied to gain an understanding of clinical complications of DM, as this population has a high prevalence of T2DM (approximately 50%). An analysis of renal complications that developed in patients with DM and periodontitis was reported [31]. None of the patients had renal disease at the beginning of the monitoring period. Following patients for as long as 22 years, those with DM and more severe periodontitis were at increased risk of developing renal disease. Compared to individuals with no or mild periodontitis, patients with moderate periodontitis, severe periodontitis, or who were edentulous were at 2.0, 2.1, and 2.6 times increased risk developing macroalbuminuria and 2.3, 3.5, and 4.9 times increased risk for developing end-stage renal disease. The study identified periodontitis as an independent risk factor for renal complications of DM. However, it is not known whether periodontal therapy would decrease this risk.

Another study [32] in the same community looked at periodontitis as a risk factor for death from cardiovascular or renal disease. With a mean follow-up period of 11 years, those with periodontitis were at increased risk of death. This was 3.2 times greater for those with severe periodontitis [32].

Other studies extend these findings, emphasizing the potential importance of periodontal disease in patients with DM. Using data from the NHANES, Demmer et al. [33], examined the transition to DM if periodontitis was present. With a mean follow-up of 17 years, compared to individuals with no or mild periodontitis, the risk of developing DM ranged from 1.5 to 2.3 for patients with moderate to advanced periodontitis. Further, the influence of periodontitis on the level of HbA1c has also been assessed [34]. Using data from a longitudinal trial in Pomerania, participants without DM were categorized by the severity of periodontitis at baseline. The change in HbA1c was examined. After 5 years, there was a fivefold increase in HbA1c when the participants with the greatest severity of periodontitis at baseline were compared to those with the least severe disease. Further, the increase in HbA1c for participants without periodontitis at baseline who did not demonstrate an increase in severity of periodontitis after 5 years was 0.005%. In contrast, patients with severe disease who demonstrated further progression demonstrated an increase in HbA1c of 0.143%.

These data position periodontal disease within the spectrum of disorders associated with dysglycemia. All healthcare professionals need to be aware of these associations, and urge patients with DM to be evaluated by a dentist at the time of their initial diagnosis, to be followed regularly by an OHCP, to practice ideal oral hygiene, and report any changes in the mouth to their health professionals.

Considering the increased prevalence of periodontitis in patients with DM, the provision of periodontal therapy should be a part of the dental healthcare services provided to affected patients. OHCPs must be aware of a variety of diet-related issues important for the appropriate management of patients. First, patient management in preparation for dental care should be concerned with avoidance of hypoglycemia during dental care. Second, maintaining an appropriate diet following surgery in the oral cavity is important to ensure normal healing and repair. Dietary modifications may be necessary postoperatively to reduce pain and maximize healing while maintaining serum glucose levels. Chapter 17 (Oral Surgery and Nutrition) addresses diet and nutrition following oral surgery and Appendix 2E has post-surgical dietary guidelines for individuals with DM.

Dental caries results from the interaction of specific bacteria (S. mutans, Lactobacillus species) that metabolize fermentable carbohydrates, the availability of the carbohydrate substrate, and a susceptible host, specifically a vulnerable tooth surface. The metabolism of the carbohydrate by the bacteria yields acid (primarily lactic acid) as a by-product, which when in contact with tooth structure for extended periods of time may lead to demineralization of the tooth substrate.

The relationship between dental caries and DM is poorly defined. This lack of clarity is due in large part to the differences in study design and a lack of clear definition of the study population (i.e., T1DM vs. T2DM, age, level of metabolic control).

The studies examining coronal caries in patients with DM have not identified DM as a risk factor for these lesions [35, 36]. A greater focus is on an association between DM and root caries. In periodontal health, the root surfaces of the teeth are not exposed to the oral environment. However, diabetes is a risk factor for periodontal disease, which is characterized by loss of periodontal attachment. One result is gingival recession and exposure of the root surfaces. Tooth root surfaces are covered with cementum, which is less densely mineralized, and much thinner than the enamel that covers the coronal portion of teeth, and in some individuals near the enamel margin, dentin is exposed. Increased root caries has been reported in patients with DM [37]. This study is noteworthy because confounders were considered, including exposed root surfaces, the level of oral hygiene, salivary gland function, and levels of cariogenic bacteria. The prevalence of root caries in patients with DM was more than twice that in the non-diabetic controls (40.0% vs. 18.5%, p = 0.001). Among the risk factors for root caries was poor buffering capacity of the saliva. Garton and Ford [38] have identified root caries as a potentially important future problem for patients with DM. As the population ages and the prevalence of DM and periodontitis increases, strategies will need to be implemented to prevent development of this complication of DM.

The importance of prevention in managing the risk of caries cannot be overstated. In addition to appropriate oral hygiene measures and the use of topical chemotherapeutic agents (e.g. fluoride), there should be a focus on salivary flow. Patients should also be counseled about the need to moderate their dietary intake of fermentable carbohydrates. Diet management for individuals with DM should be tailored to the patient’s diabetes diet plan and focus on integrating oral hygiene practices with meals and snacks. Dietary guidelines to reduce caries risk are addressed in more detail in Chapter 1.

Xerostomia is the subjective complaint of mouth dryness. Xerostomia is associated with hyposalivation, which is reduced production of saliva.

A complaint of xerostomia and reduced production of saliva has been reported in patients with DM. This complication occurs at all ages, including adolescents [39], adults [40], and older adults at least 60 years of age [41]. In case–control studies, the number of individuals with DM who complain of xerostomia is 50–100% greater than individuals without DM. The proportional reduction in salivary flow was greater in the resting rather than the stimulated state [40].

Saliva has a number of important functions. This fluid lubricates the oral cavity, which allows comfortable oral function, i.e., softening the bolus of food and wetting the surfaces of the teeth and mucosa and reducing the chance of mucosal abrasion from hard or crusty food. The constituents of saliva also include amylase, which begins the process of digestion of starch in food. Saliva also contains different antimicrobial constituents such as lysozyme, peroxidase, and defensins, which helps to control the oral microflora. The buffering capacity and supersaturated calcium and phosphate of saliva are also critical, specifically to neutralize acids produced by bacteria when fermentable carbohydrates are metabolized and to remineralize teeth. This buffering affect is seen most strikingly with patients who lose salivary function secondary to radiation of the head and neck. Rampant caries can result.

When salivary flow is reduced, clinically important problems occur. As noted, the buffering capacity of saliva means that the fluid is an essential host mechanism to prevent tooth demineralization as a result of acid production following carbohydrate metabolism. Prevention includes diet instruction, plaque control, the use of topical fluoride, or fluoride delivered via mouth trays [42] and consideration for use of remineralizing products and chlorhexidine for antimicrobial effect. These measures may need to be considered for patients with T1DM or T2DM. Saliva provides a supersaturated calcium and phosphate source for remineralization of the dentition. Saliva also has antimicrobial and clearance functions. Bacteria and other microorganisms that are disrupted and separated from the plaque biofilm and degenerated epithelial cells are cleared from the oral cavity when swallowing occurs, and swallowing is far more efficient when there is a normal amount of saliva. A reduction or virtual absence of saliva may not only hamper digestion, but also makes eating difficult and less enjoyable. The absence of this lubricating effect of saliva and a reduction in enjoyment of eating are often the basis for patient complaints. Reduced salivary flow is a cause of reduced quality of life [39], and can be of major significance when patients with DM also suffer from medical complications of their disease.

Hyposalivation can have a significant impact on dietary intake and therefore nutritional status. Dietary management for patients with xerostomia and reduced salivary flow focuses on adequate fluid intake with all meals and snacks, avoidance of citrus fruits and juices, and other high acid foods and fluids as well as sugar sweetened beverages. Ingestion of moist foods is encouraged to reduce mucosal irritation (see Appendix 2C for dietary-guidelines for patients with xerostomia). Saliva secretion can be enhanced by taste, the chewing function, systemic sialagogues, and palliation provided with topical treatments. Therefore, it is critical that the OHCP and RD collaborate to develop an effective dietary management plan for patients with DM who have reduced salivary flow. It is important to remember that improved metabolic control of DM may improve salivary flow.

Candida albicans, and to a lesser extent other Candida species, commonly exist as commensal organisms in the human oral cavity. However, in a number of conditions, including DM, acquired immunosuppression (e.g., HIV infection) and prolonged use of corticosteroids or antibiotics, Candida can cause disease in humans.

Candida infection in the oral cavity can present as a number of different lesions. This variability can make diagnosis a challenge. The lesions include:

Pseudomembranous candidiasis: erythematous (red) lesions with white patches. The white patches are accumulations of fungal organisms.

Atrophic or erythematous candidiasis: erythematous mucosa without white patches. If the dorsal surface of the tongue is involved in pseudomembranous or atrophic forms of candidiasis, the lesion has been referred to as medium rhomboid glossitis. When involving the hard palate, the lesion is often present under a complete upper denture or under partial denture bases. This lesion appears velvety and is referred to as denture stomatitis.

Hypertrophic candidiasis: mucosal hyperplasia with areas of increased keratin thickness. This lesion is a tissue response to an invasive Candida infection.

Angular cheilitis: fissures at the corners of the mouth. These lesions demonstrate fungal hyphae when a smear is taken.

Guggenheimer et al. found that a higher percentage of patients with T1DM versus control subjects have clinical manifestations of candidiasis, including median rhomboid glossitis, denture stomatitis, and angular cheilitis (15.1% vs. 3.0%) [43]. Subjects with T1DM were also more likely to have Candida pseudohyphae in their cytologic smears. Diabetic subjects with medium rhomboid glossitis had a longer duration of T1DM as well as the microvascular complications of nephropathy and retinopathy. Denture stomatitis was associated with smoking, retinopathy, higher counts of candidal pseudohyphae, poor glycemic control, and a longer duration of T1DM. Three factors in this study associated with the presence of candidal pseudohyphae were cigarette smoking, the use of dentures, and elevated HbA1c levels, indicative of marginal to poor metabolic control.

The overgrowth of oral Candida in patients with DM has been linked to the concentration of glucose in saliva [44] and altered PMN function (phagocytosis and intraoral killing of Candida) in patients with DM has also been identified [45]. Treatment with antifungal therapy and elimination of the Candida infection was accompanied by an improvement in PMN function. The improvement, however, was not to the level observed in normal individuals.

Increased oral colonization and overgrowth of Candida have been linked to the presence of a removable denture. Erythematous mucosa under the acrylic portion of the denture is the characteristic clinical finding (also referred to as denture stomatitis), and increased Candida colonization was reported in patients with DM and with a denture, and a higher percentage of patients with DM demonstrated denture stomatitis [46].

The presence of clinical infection due to Candida species (candidiasis) in the oral cavity should lead to a search for underlying risk factors. It is important to emphasize that many risk factors for intraoral candidiasis exist, and a thorough patient history is essential to establish the underlying cause.

Burning mouth symptoms occur in patients with DM, but are not unique to these patients. This may be related to mucosal lesions, candidiasis, or dry mouth. Burning mouth syndrome (BMS) is characterized by a bilateral burning sensation without mucosal lesions. Patients affected with BMS commonly complain of burning or irritation, often involving the tongue and less often other sites on the lips and palate. Additional complaints include disturbances in taste, and a complaint of mouth dryness. Underlying oral disorders that may also be associated with DM should be ruled out such as Candida infection and lichen planus and treated if necessary. Burning mouth syndrome is rarely associated with vitamin and mineral deficiency, and anemia [47].

If other causes are ruled out, BMS may be a manifestation of diabetic neuropathy [48]. This case report illustrated a patient with these symptoms, and very poor metabolic control (fasting plasma glucose of 395 mg% and an HbA1c of 14.1%) was identified; oral symptoms improved with improved metabolic control. However, a study of BMS and diabetic neuropathy in patients with T1DM illustrates the challenges associated with identifying BMS as a manifestation of diabetic neuropathy [49]. A total of 371 adults with T1DM and 261 individuals without diabetes that served as the control group were evaluated. The prevalence of BMS in the entire cohort was 4.6%. After eliminating the patients with identifiable causes (primarily candidiasis, with different clinical manifestations), the occurrence of BMS was 3.2% in the patients with T1DM and 2.1% in the control subjects. A more detailed analysis of the 12 patients with T1DM and BMS revealed that significant risk factors included a previous diagnosis of diabetic neuropathy (p = 0.024) and female gender (p = 0.042). Diabetic neuropathy is a challenge to treat; treatment focuses on improved metabolic control of diabetes and management of pain. Pain management strategies focus on the use of centrally acting medications used to treat neuropathic pain, including anticonvulsant, anti-anxiety and antidepressant medications [50]. Unfortunately, many of the medications have xerostomia as a side effect that may complicate the oral/dental management of these patients.

There are a number of other oral lesions that have been associated with DM. These include aphthous stomatitis [51], lichen planus [52], and benign parotid enlargement [53]. These lesions have not been comprehensively studied, occur infrequently, or occur in association with many conditions, and when DM is not present. In addition, taste alterations/bad taste have also been identified as a complaint of patients with DM, which in at least some cases is related to reduced salivary flow, changes in salivary chemistry, Candida infection, or in association with BMS.

Considering the different oral lesions that have been associated with DM, evidence suggesting that untreated periodontitis can adversely affect metabolic management, and the increasing prevalence of diabetes in the U.S. population, OHCPs can have an important role in patients with diabetes and in identifying patients with undiagnosed or poorly managed DM. The outcome of dental care can be optimized by collaborating with other healthcare professionals to assure that patients maintain as close to an ideal blood glucose level as possible. For chronic disorders such as DM, where focus needs to be on lifestyle modifications (including diet, exercise, and weight control) as well as the use of oral medications and insulin, different contacts with the healthcare system provide opportunities for monitoring and reinforcement of therapeutic goals.

All health professionals must be cognizant of the medical, dental, and nutrition goals for management of diabetes, be aware of the resources available, and refer the patient to the appropriate healthcare provider. No discipline functions within a vacuum; in particular, in regard to dentistry and nutrition, there is a need for awareness of the important role each healthcare professional plays in the management of patients with DM.

It is incumbent on nutrition and oral healthcare professionals to screen individuals with DM for nutrition and oral health risks, provide appropriate education, and when necessary, referral to other health professionals. The relation between oral manifestations of DM and diet/nutrition is complex and bidirectional. Oral manifestations of diabetes challenge and compromise eating ability and consequently diet quality and nutrient intake, ultimately impacting nutrition status. A detailed review of oral nutrition risk assessment may be found in Chapter 19.

Population screening for DM is controversial. However, targeted cohort screening is indicated for high-risk individuals, especially when screening can occur as part of another healthcare activity, and when at-risk individuals gather in one location.

In recent years, there has been increasing interest in the idea of assessing the risk for diabetes in the dental office, and using oral/dental data to help with this assessment. This interest is driven both by the realization that nearly 70% of adults have seen a dentist in the past year [2], and that the dental disease and oral lesions associated with DM may be the reason that a patient seeks dental care.

Li et al. [54