**3.1. Tooth formation**

Moreover, Insulin may indirectly regulate the enhancement of growth hormone (GH) serum concentration by direct regulation of the hepatic growth hormone receptor, this results in abnormalities in the insulin growth factor-1 (IGF-1) in T1DM [52] which consequently may

In the present study most of the periosteal surfaces in the mandibular regions of the control group showed significantly higher values recorded for the mineral apposition rate and the bone formation rate when compared to the DM group. These results agree with previous studies that recorded diminished lamellar bone formation in DM rats' femur and may sug‐ gest an association between the DM condition and the decreased number and function of osteoblasts [16, 19]. The alveolar crest region was the only region that did not show a signifi‐ cant difference in the mineral apposition rate and the bone formation rate parameters among the two groups; this may be attributed to the unique nature of this region exhibiting a highly intensive bone remodeling process especially during the teeth eruption that de‐

A significant decrease of bone volume fraction, trabecular thickness, and trabecular numbeis confirmed by Micro-CT analysis in DM rats, there was Also, it showed a significant increase of the trabecular separation and the trabecular space in the DM group when compared with the control group. This finding indicates deterioration of the bone quality in the DM group. These results agree with other research work suggesting that the glycaemic levels play an important role in modulating the trabecular architecture especially in mandibular bone [15]. In this context, these results may describe a state of osteopenia in experimental diabetic rats,

A histometric evaluation of bone resorption was performed by counting the number of os‐ teoclast cells on the distal surface of the alveolar bone adjacent to the mesio-buccal root of the second molar. These evaluations revealed that the number of osteoclasts was significant‐ ly lower in the DM rats than in the controls, in line with previous studies on DM rats' man‐ dible [40] and long bones [41, 42]. These studies confirm that the decreased rate of bone

This deteriorating effect on mandibular bone structure and dynamic bone formation might be be attributed to several pathogenic possibilities, such as insulinopenia, bone microangi‐ opathy, impaired regulation of mineral metabolism, alterations in local factors that regu‐ late bone remodeling, and even an intrinsic disorder associated with DM [12, 37]. However, the detrimental effects observed may not be associated with the significant loss of rats` weights observed in the diabetic group starting from day 14 because previous research [2, 12, 15, 42] showed that the mandibular growth was not affected in normal rats supplied with restricted diet and having same pattern of weight loss resembling weight loss pat‐

which might be the result of an imbalance between bone formation and resorption.

have lead to the retarded growth in uncontrolled DM in the current study.

creases toward the base of the socket [33].

422 Type 1 Diabetes

turnover may be associated with the DM condition.

tern observed in DM rats.

Tooth growth begins before birth and continues throughout adolescence. The dental develop‐ ment is a continuous process of tooth initiation, matrix secretion, crown mineralization, den‐ tal eruption, and root completion. Primate dental development begins before birth with initiation of the deciduous dentition, followed by initiation of the permanent dentition. During the process of dental eruption the tooth must move past the bone margin (alveolar eruption) and the gum (gingival eruption) in order to emerge into the oral cavity and eventually into functional occlusion. Dentine is formed when odontoblasts secrete a collagenous matrix predentine which rapidly undergoes mineralization to form primary dentine. Dentine formation begins at the dentine horn underlying the future cusp tip and progresses inward through secretion and downward through extension until it reaches the apex of the root. Enamel is formed when ameloblasts secrete enamel matrix proteins that mineralize into long, thin bundles of hydrox‐ yapatite crystallites known as enamel prisms. As the secretory cells progress outward to‐ ward the future tooth surface, additional adjacent cells are activated through extension until the forming front reaches the cervix of the crown [3].

The resistance of the dental tissues to caries is determined by the quantitative content of the inorganic and organic matrices. Numerous reports have showed that teeth with a correct macro- and microstructure and a proper degree of mineralization are more resistant to the activity of external cariogenic factors [3].

Several biological complications in patients suffering from type 1 diabetes mellitus have been widely investigated over the previous years, however, the scientific data available on the possible effects of T1DM on teeth are scant. These data suggest that T1DM condition may be associated with a change in the chemical composition of the teeth or alteration in the total thickness of enamel or dentin.

Various clinical studies on children reported high caries prevalence in diabetic children when compared with healthy controls [3]. This high caries prevalence may be associated with factors affecting the tooth structure itself or due to some changes in the oral environ‐ ment causing the increase of the susceptibility of the teeth to dental caries.

#### **3.2. Effects of Type 1 Diabetes on tooth mineral composition**

Proper mineralization of teeth during its development is the key factor for the proper resist‐ ance of teeth to cariogenic challenge and thus any metabolic disorder affecting the teeth mineralization during its development may render these teeth more prone to be involved by caries. Rat experimental model provides an excellent model for the study of the various met‐ abolic disorders on the mineralization of teeth hard tissues due the fact that the rats incisors are continuously growing and erupting during its life and thus it is possible to study vari‐ ous effects of metabolic disorders which can be induced artificially during the growth peri‐ od of these rats [53]. The results obtained from the aforementioned experimental rat model can be compared to the results obtained from control rats living under identical situations and thus can easily eliminate many variables that can affect the outcome of the results of any experiments conducted on humans.

**4. Conclusions**

analysis.

in these patients.

It is obvious that the T1DM condition significantly affects craniofacial growth, bone forma‐ tion mechanism and the quality of the bone formed which may alter many aspects of plan‐ ning and treatment of orthodontic patients affected by this globally increasing hormonal disturbance. Moreover, T1DM condition impairs the proper tooth development and alters

The Effect of Type 1 Diabetes Mellitus on the Dento-Craniofacial Complex

http://dx.doi.org/10.5772/52973

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There should be a new strategy for treating orthodontic patients suffering from metabolic disorders specially those disorders having direct and indirect effects on bone growth as the diabetic condition. The orthodontic craniofacial linear measurements were significantly de‐ creased in the T1DM cases when compared to normal cases. Moreover, greater risks of de‐ veloping dental caries and possible tooth loss are associated with patients suffering from T1DM; these risks may complicate the outcome of orthodontic treatment which is associated with less ability of orthodontic patients to implement proper oral hygiene measures due to

These comprehensive studies done on bone and craniofacial growth suggest that planning the treatment in craniofacial region for patients affected with hormonal disorders is a more complex procedure when compared to the treatment of normal patients, moreover it is sug‐ gested that it is of prime importance to keep close attention to the general systemic condi‐ tion of these patients and administer the proper hormonal therapy for these patients when needed to avoid any detrimental effects on bone resulting from any hormonal imbalance. Moreover, it is highly recommended to closely monitor the salivary and the dental condi‐ tions of these patients to allow early intervention for treating any developing dental caries.

**1.** T1DM reduces craniofacial growth, resulting in retardation of skeletal development.

**2.** DM in the rat affects the bone architecture, as shown by Micro-CT, and impairs the rate of the mandibular bone formation, as examined by the dynamic histomorphometric

**3.** All of these results were verified on the cellular level by a histological study that showed the diminished number of osteoclasts on the alveolar wall, suggesting that the

**4.** These findings should be considered when conducting any treatment in the craniofacial region in T1DM since the better understanding of how diabetes affects bone will im‐

**5.** The tooth structure and the saliva condition are negatively influenced by the T1DM condition and thus strict oral hygiene measures should be conducted with orthodontic patients suffering from T1DM condition to decrease the risk of developing dental caries

the oral environment rendering teeth more susceptible to dental caries.

increased areas of bacterial biofilm formation around orthodontic brackets

Within the limitations of this *in vitro* study, it was concluded that:

early stage of DM resulted in low bone turnover.

prove our ability to protect bone health in diabetic patients.

In vitro studies on animal models affected by the streptozotocin induced diabetic condition showed that there is a low concentration of calcium and fluoride in the growing rats` inci‐ sors after inducing the diabetic condition by the streptozotocin injection [54]. Moreover, there was a concomitant increase in the concentration of calcium in blood serum and a decrease in fluoride concentration in blood serum. It was suggested that the decrease of calcium concen‐ tration in the teeth structure in this study was due to decrease of the cellular activity of ameloblasts during the enamel development [54]. This suggestion may be backed by the results obtained from a similar streptozotocin induced diabetic rat model which showed that the diabetic condition is associated with a decrease in the calcium deposition in bone due to a generalized metabolic activity decrease [12, 28]. The recorded increase in calcium in blood serum was attributed to the absence of insulin which aids in the transfer of calcium from the blood serum to the body tissues. The low concentration of fluoride observed in the tooth structure and in the blood serum may be attributed to the incorporation of the fluoride in bone matrix which is induced by the high concentration of the estrogen observed in the blood serum [54]. Moreover, the increase in fluoride elimination in urine may have caused this decrease in fluoride concentration in the diabetic rats.

#### **3.3. Effects of Type 1 Diabetes on salivary status**

The saliva contents and rate of flow are among the critical factors that predict the caries inci‐ dence in the oral cavity. Type 1 DM is among the endocrine disease that elevates the glucose level concentration in saliva and decreases the salivary rate of flow.

The mechanism by which the glucose level may increase in saliva may be explained by previous research showed that the increase of blood glucose level in T1DM cases is associated with a concomitant increase of glucose level in saliva. Moreover, it was previously suggested that T1DM causes an increase in the permeability of the basement membrane of the parotid gland that favors the transfer of glucose from the parotid gland to the saliva in the oral cavity [3].

The mechanism by which T1DM decreases the salivary flow may be attributed to the detri‐ mental effects induced by the T1DM condition on the salivary gland tissues itself causing a generalized decrease in the saliva in the oral cavities.

The factors of increased glucose level and decrease in salivary flow cause the improper clearance of glucose from the oral cavity and impairs the buffering capacity of saliva rendering it more acidic, these aforementioned effects consequently increase the metabolic activities of the bacterial biofilm in the oral cavity and render teeth more susceptible to dental caries [3].

Previous research work [3] showed that the dietary habits conducted by the diabetic pa‐ tients do not have a significant effect on the prevalence of caries in these patients when com‐ pared to normal individuals and thus it may be concluded that the increase in caries prevalence in diabetic patients is likely associated with factors affecting the development of teeth or due to some detrimental effects induced by the oral environment that increases the risk of caries occurrence in oral cavities of T1DM patients.
