Diabetes and periodontics

The potential use of gingival crevicular blood for measuring glucose to screen diabetes;

M strauss; j. wheeler j p 2009;80;907-914

Presented by, Dr. Muzafar 3nd Year MDS

• Under The Guidance Of,

Dr. Suhail Majid jan

Guide & Head

Dr. Mehraj kirmani

Dr. Faiza yaqoob

Ragistrar

• DIABETES;- Diabetes mellitus (DM) refers to a group of common metabolic disorders that share the phenotype of hyperglycemia (Harrison’s)

INTRODUCTIONDEFINITIONCLASSIFICATIONDIAGNOSISPATHOGENESISTYPE-1 DMTYPE-2 DMCOMPLICATIONSACUTECHRONICEffect of dia.on periodontitisEffect of periodontitis on dia

• Classification:-• DM is classified on the basis of the pathogenic process

that leads to hyperglycemia, as opposed to earlier criteria such as age of onset or type of therapy.

• The two broad categories of DM are designated type 1 and type 2. Both types of diabetes are preceded by a phase of abnormal glucose homeostasis as the pathogenic processes progress.

• Type 1 DM is the result of complete or near-total insulin deficiency.

• Type 2 DM is a heterogeneous group of disorders characterized by variable degrees of insulin resistance, impaired insulin secretion, and increased glucose production


• Other Types of DM

• Other etiologies for DM include specific genetic defects in insulin secretion or action, metabolic abnormalities that impair insulin secretion, mitochondrial abnormalities, and a host of conditions that impair glucose tolerance

• Maturity-onset diabetes of the young (MODY) is a subtype of DM characterized by autosomal dominant inheritance, early onset of hyperglycemia (usually <25 years).


• DM can result from pancreatic exocrine disease where majority of pancreatic islets are destroyed; Cystic fibrosis-related DM . Hormones that antagonize insulin action can also lead to DM; such as acromegaly and Cushing's disease. Viral infections have been implicated in pancreatic islet destruction; rare cause of DM. A form of acute onset of type 1 diabetes, termed fulminant diabetes, has been noted in Japan.


– Gestational Diabetes Mellitus (GDM)

• Glucose intolerance developing during pregnancy is classified as gestational diabetes.

• Insulin resistance is related to the metabolic changes of late pregnancy, and the increased insulin requirements may lead to IGT or diabetes; most women revert to normal glucose tolerance postpartum but have a substantial risk (35–60%) of developing DM in the next 10–20 years.

• The International Diabetes and Pregnancy Study Groups now recommends that diabetes diagnosed at the initial prenatal visit should be classified as "overt" diabetes rather than gestational diabetes.


»Diagnosis:- Wang Shou in752 A.D, for the 1st time

recommended a special method of testing sugsr in urine , by asking the pt to pass urine on a wide, flat brick to see if ants gathered or not.

Before 1975, physicians utilized evaluation of urine glucose levels as a screening and monitoring mechanism, but was insensitive hence, replaced by blood glucose test (Diabetic care 1995).


GLYCEMIC TEST FOR GLUCOSEHyperglycemia is hallmark of diabetic state and easy to quantify. Methods used to diagnose diabetes mellitus and monitor its levels are fasting blood glucose, a combination of fasting plus a 2- hour postprandial and oral glucose tolerance tests. Oral Glucose Tolerance Test (OGTT) Oral glucose tolerance test with plasma glucose value of 200 mg/dl or more , 2 hours after a person has consumed 75 grams is considered positive . A negative diagnosis is definitely confirmed with a negative for OGTT.Any stress, physiological, psychosocial, or pathophysiologic factors could result in false positive result.


• American Diabetic Association in 2004

Criteria for fasting plasma glucose(FPG)1. FPG<100mg/dl --------------------normal fasting

glucose2. FPG>100MG/dl and <126mg/dl------imp fasting

glucose 3. FPG>126mg/dl ---------------------diagnosis of diabetes

Criteria for 2-hour post-prandial glucose (2hPG)1. 2hPG<140mg/dl---------------------normal glucose

tolerance2. 2hPG>140mg/dl and <200mg/dl-------impaired

glucose tolernce3. 2hPG>200mg/dl----------------------diagnosis of

diabetes


• Glycosylated hemoglobin• Rahbar in 1968 1st described glycosylated

hemoglobin test. However, became available for use in 1970s.

• It measures the amount of glucose irreversibly bound to the hemoglobin molecule.

• it gives measurement of blood glucose levels over 30 to 90 days.

• Two different glycosylated hemoglobin tests are available:

• Hemoglobin A1(HbA1) test-----<8.0%• Hemoglobin A1c(HbA1c) test----<6.0 to 6.5%.

• Due to fluctuation of plasma glucose levels, this test reflects a more stable monitor of the therapeutic glycemic control


• Fructosamine test;- Glucose attaches to a molecule of

protein, the biochemical structure resembles a fructose molecule, hence named as..

Developed in 1982 by johnson RN as monitoring test.

Half life of serum proteins is 1 to 3 weeks, so it is useful in monitoring the diabetic control over a short period of time.

Normal range is 2.00 to 2.80mmols/l.

false +ve in renal failure or liver disease .

INTRODUCTIONDEFINITIONCLASSIFICATIONDIAGNOSISCOMPLICATIONSACUTECHRONICEffect of dia.on periodontitisEffect of periodontitis on dia

• Glucometers;- Development of glucometers was a

major breakthrough in the history. Provided diabetic patients an

opportunity for rapid and accurate home monitoring of their blood glucose levels,

Thus improving control of their glucose levels.

Skyler JS et al: diabetes care 1978


complications:;- Acute complications;-People with diabetes can go from healthy and active to unconscious-in a matter of minutes, Hypoglycemia:-sugar level <60mg/dl and is most common complication of insulin-treated diabetics.

Sense of hunger initially, Followed by irritability, Tachycardia, Palpitations and cold sweat, Leading to decreased mental abilities, confusion

and coma.

Immediate treatment consists of administration of glucose, in oral or parental form


Reduce hypoglycemia during dental procedure, pt should be scheduled early in the morning after their regular intake of food.

If they are on insulin, dosage modification should be made to accommodate for delayed or reduced oral intake.


• Diabetic ketoacidosis (DKA);-• Unrecognized or untreated insulin deficiency

(type 1 diabetes) or any sever stress .• Inadequate glucose utilization leads to

unregulated lipolysis with formation of free fatty acids that are converted to ketones

• Toxic products build up in the bloodstream, causing nausea and vomiting, fever, malaise, headache, abdominal pain, shortness of breath, acidosis and then coma and death if left untreated.

• all the diabetics are encouraged to monitor urine ketones when blood sugar exceeds 240 to prevent the development of ketoacidosis.


• Chronic complications;- chronic complications of diabetes mellitus

affect many organ systems and are responsible for the majority of morbidity and mortality.

Chronic complications can be divided into vascular and nonvascular complications. The vascular complications are further subdivided into microvascular and macrovascular complications .


• Chronic Complications of Diabetes Mellitus Microvascular

Eye disease Retinopathy (nonproliferative/proliferative) Macular edema

NeuropathyNephropathy

MacrovascularCoronary heart diseasePeripheral arterial diseaseCerebrovascular disease

Other Gastrointestinal (gastroparesis, diarrhea) Genitourinary (uropathy/sexual

dysfunction) Dermatologic, Infectious, Glaucoma Periodontal disease


Diabetes and periodontitis:= effects of hyperglycemia;-

Metabolic dysregulation in diabetes due to prolonged increased levels of glucose leads to glycosylation of long lived proteins and lipids ; these products are referred as advanced glycosylation endproducts (AGEs).

AGEs were identified in 1912 by louis Mallard..

These nonenzymatic products are responsible for sequelaev of diabetes such as vascular lesion; neuropathy and impaired immunologic functions (brownlee M 1994)

INTRODUCTIONDEFINITIONCLASSIFICATIONDIAGNOSISCOMPLICATIONSACUTECHRONICEffect of dia.on Periodontium Effect of periodontitis on dia

• Chronic hyperglycemia promotes glycosylation of hemoglobin to form Aic ; measurement of HbAic is most reliable to measure glycemic control for 3-months.

• Receptors for AGEs (RAGEs) were 1st identified by Neeper M 1992; multi-ligand receptor that propagates cellular dysfunction in inflammatory disorders, tumors and in diabetes ;


• Interaction of AGEs-RAGEs complex results in;-– Alteration of signal transduction pathways;

alteration in hormones, cytokines and free radicles (vlassara H 2002)

– Binding of AGEs to monocyte receptors ; induces production of IL-1, insulin like growth factor-1 tumor necrosis factors and platelet- derived growth factor ( sharma JN 2005)

– Alter cellular function via binding to cultured endothelial cells and mononuclear phagocytes ( salvi GE 2005)

• Thus binding of AGEs macrophages and other cell types contributes to increased cytokine production leads to; atherosclerosis or CHD and more sever and progressive form of periodontal disease.( Lalla E 2000)


• Diabetes and periodontal disease;- Diabetic patients have been shown to be at

increased risk for infections (Kottra CJ 1983).

Periodontal disease is one of the most prevalent complications of diabetes (Hallmon WW 1992).

Diabetes carries 2 to 3 times higher risk for both sever periodontitis and the incidence of periodontal disease progression (taylor GW 2001)

Exacerbation of host immunity that is triggered by bacteria found in periodontal lessions (Kinane DF 2000).


Components of bacteria, such as lipopolysaccharide found in their cell membranes, are potent stimulator of cellular secretion of cytokines and growth factors via toll-like receptor-mediated response (Gamonal J 2000)

Lipopolysaccharide binds to toll-like receptor 4 (Pugin J 1994)

Toll-like receptor activation leads to activation of kinase complex, production of innate inflammatory cytokines, leads to tissue damage and destruction (Wesche H 1997)


• Cytokines that are released following stimulation are; IL-1ß, IL-6, tumor necrosis factor-α and prostaglandin E2.

• So periodontal tissue destruction is consequence of an exaggerated monocytic inflammatory response induced by AGEs and increased secretion of local and systemic mediators leading to severe periodontitis.


• Potential mechanisms increasing the risk of periodontal complications in diabetics;-– The pathogenesis of periodontal disease is

complex because it reflects a combination of the initiation and maintenance of the chronic inflammatory process by diverse microbial flora and their numerous products.

– And diabetes is the prominent factor which exaggerates the host response to these bacteria and their products by various mechanisms as given by pour et al 1983.

Impaired neutrophil function; Collagen metabolism and AGEs Altered monocytic and immune response Vascular abnormalities Imbalances in lipid metabolism Impaired wound healing Infections in patients with diabetes.


• Studies on effects of diabetes on periodontium

Hirschfeld in 1934; described the gingival effects of diabetes as; sessile or pedunculated polyps;

Glickman in 1946 there were changes in bone formation and increase bone resorption .

Benveniste et al 1967 compared the periodontal status of diabetic and non-diabetic pts, and found diabetic pts have higher frequency of gingivitis , pocket depth and bone loss


Authors Comparison p. parameters results

Cohen et al 1970 21 diabetics 18 nondiabetics

Plaque score, periodontal scores

Both scores were higher in diabetics

Nichols et al 1978 54 diabetics aand nondiabetics

Periodontal status using Ramfjords PDI

Gingival index and plaque index were higher in diabetics than controls

Firatli et al 1994 Type 1 pts Glycemic control and bleeding on probing

Salvi et al 2005 Diabetics and non-diabetics

Plaque score and bleeding on probing

Diabetics pts develop early and higher inflammation

Ainamo et al 1996 Diabetic pts Glucemic control and periodontal destruction

Poorly controlled diabetes higher destruction and bone lose

Tervoneen et al 1986

50 diabetics and same non-diabetics

Prevalence of p.pockets and bone loss

Prevalence of pocket formation and bone loss declines with dia, control

Arrieta-Blanco et al 2003

74 diabetics and 70 non-diabetics

Gingival status, pocket depth, attach loss, gingival recession and CPITN score

Statistically higher gingivitis index, loss of attachment and recession in diabetics

Cutler et al 2000 Diabetic pt Periodontal destruction and diabetic control

Except plaque all indices were elevated in pooly controlled diabetic pts

• Effect of periodontal therapy on diabetes;-

Periodontal diseases are bacteria-induced infections affecting the periodontium and resulting in the loss of tooth attachment. These bacteria can invade endothelial cells and is a potent signal for monocyte and macrophage activation.

once established in the tissue, this chronic infection complicates diabetes control and increases the occurrence and severity of microvascular and macrovascular complications.

These pathogen cause a chronic local lowgrade inflammation and contribute to systemic inflammation.


This is reflected by higher circulating levels of inflammatory markers such as C-reactive protein, IL-6 and TNFα,

responsible for worsening insulin resistance and diabetes (Nishimura 2000)

Taylor jp 1996 severe periodontitis are more likely to develop impaired fasting glucose (IFG), impaired glucose tolerance (IGT), or diabetes mellitus than patients with moderate periodontitis


Taylor et al 1999 ; found that at the 2-year follow-up, patients with severe periodontal disease were 1.5 to 3.4 times more likely to have IGT and/or diabetes than patients without severe periodontal disease.

Saito et al j dent res 2004. showed that patients with gingival pockets greater than 2 mm in depth were significantly more likely to have IGT than patients with pockets less than 1.3 mm .

Because of this relationship, the diabetes specialist should put an emphasis on oral health and its control as an integral part of diabetes treatment.


• Treatment;-• Stewart et al jcp 2001 mechanical treatment (eg,

ultrasonic scaling and root planing) led to significantly reduced HbA1c levels in patients with periodontitis and type 2 diabetes mellitus , compared with an equal number of individuals who received no periodontal treatment. Patients in the treatment group had, on average, a 17.1% reduction in HbA1c levels at 10 months follow-up.

• Kiran et al jcp 2005 patients with type 2 diabetes mellitus who received periodontal therapy (both surgical as well as nonsurgical) for periodontal disease had, on average, a 10.94% reduction in HbA1c levels at 3 months follow-up. This reduction compared with a 4.42% increase in HbA1c levels in the control group.


• Antibiotics;-Miller et al jp 1992 usefulness of mechanical debridement, chlorhexidine rinse (30 seconds twice daily), and doxycycline (100 mg twice daily for 1 day, once daily for 13 days), showed improved periodontal status as manifested by reduced bleeding during probing of the gingival sulcus, and significant decrease in HbA1c levels, from 8.7% to 7.8%.

Grossi et al jp1997 diabetes mellitus pts , treated with mechanical débridement and systemic doxycycline had significant decreases in HbA1c levels at 3 months follow-up


Grossi et al concluded that the doxycycline causes reduction in the periodontal infection and inflammation, leading to decreased TNF-α levels, also causes reduction in nonenzymatic glycation— that is probably a factor in decreased HbA1c levels.

Rodrigues et al jp2003 treatment of diabetic patients by mechanical treatment combined with amoxicillin and clavunate combination therapy for 15 days, reported that these patients had significant reduction in HbA1c levels


• The potential use of gingival crevicular blood for measuring glucose to screen diabetes;

• M strauss; j. wheeler j p 2009;80;907-914

• Considerable efforts were made in past to develop painless and noninvasive methods to measure blood glucose.(Ervasti T J.P 1985)

• Glucometers are commonly used by diabetic patients for monitoring of blood glucose levels at home.

• Periodontal inflammation, with or without the complicating factor of diabetes mellitus, is known to produce ample extravasated blood during a periodontal examination (Kost J 1997)

INTRODUCTIONAIMMATRRIAL AND METHODSSTATISTICAL ANALYSISRESULTSDISCUSSIONCONCLUSION

• Routine probing during periodontal examination are more familiar to practitioner and less traumatic compared to a finger-puncture with sharp lancet,

• These devices actually allow painless testing of blood oozing from gingival crevices of pts with periodontal problem during routine examination

• Its simple and relatively inexpensive in-office screening device for any pts

• Recently, more sensitive self-monitoring devices have been developed for testing small amounts(2μl) of blood and have high accuracy( Rheney CC2000)


• Aim ;-– The aim of the present study was to

assess reliability of a glucose self-monitoring device for testing crevicular blood glucose, comparing crevicular and fingerstick blood glucose measurements with standard laboratory venous blood glucose measurement in diabetic and non-diabetic patients.


Material and methods;-The study population included 30 diabetic patients with moderate to sever periodontitis and also 30 non-diabetic patients were randomly selected from individuals attending the department


• Exclusion criteria;-I. History of bleeding disorderII. Anti-coagulant therapyIII. Salicylates, acetaminophen, ascorbic acid

other reducing agents.IV. Conditions affecting hematocrit(anemia,

polycythemia)V. Systemically compromised (cardiovascular,

hepatic, renal, hematological disorder.VI. Requiring antibiotic premedication


• Gingival capillary blood sampling;• Gingiva in relation to maxillary anterior

teeth was chosen for sample collection, as they offer ideal access.

• Site with more visible changes of inflammation was selected as test site.

• Isolation was done with cotton roll and salivary contamination was prevented by gauze squres and air drying.

• standard periodontal examination using williams probe ( probing force app 0.2N)


• Blood oozing from gingival cericular fluid was used for glucose assessment.

• Glucometer is turned on by inserting reagent strip into the test port, top edge of the strip is placed against the bleeding site.

• Blood is automatically drown into reaction cell of the strip by capillary action until confirmation window is full before meter begins count down


Finger stick capillary blood sampling;- finger stick capillary blood (CFBG) was

collected from the lateral surface of the fourth finger of the left hand due to thinner epithelium and also of lesser use.

Soft surface of the fingertip was wiped with surgical spirit (70% iso propyl alcohol) and then allowed to evaporate.

The finger was punctured with sterile lancet.


1st drop was wiped away and 2nd drop was used for analysis.

The test was then performed by same glucometer as used in previous test.


• Laboratory blood sampling;-– The patient was then subjected for glucose

estimation at hospital using venous blood from ante-cubital vein.

– The venous blood (3ml) was collected in a vacuum tube containing EDTA.

– Sample was centrifuged to obtain plasm.

– The resultant plasma is analyzed for glucose using computerized automated laboratory glucose analyzer,

– Which employs glucose oxidase method and gives results in mg/dl


• The gingival , finger-stick and venous blood sampling took about 30 minutes to complete and are considered to be near simultaneous measurements.

• All results were documented.


• Statistical analysis;-– Analysis was performed by

pearson product moment correlation


• Results ;-– The difference between the measurements in

the same individual was tested by paired ‘t’ test.

– Pearson’s correlation coefficient was used to assess the relationship between different measurements.

– The result of our study revealed a strong correlation (r=0.9814,p<0.001) between gingival crevicular and peripheral capillary blood (range from 3.57mmoles/l to 18.01mmol/l)


• Group1;- diabetic pts with chronic periodontitis)– The mean fasting glucose level at GCB was

124±26.5 mg/dl, FP was 118.5±24.5 mg/dl and IVB was 112±25.4mg/dl.

– statistically significant correlation (p level <0.001) was found between GCB and FP (r=0.99) and IVB (r=0.98) and FP with IVB (r=0.99).

• GroupII;- non-diabetic pts with chronic periodontitis– Mean fasting glucose level at GCB was 103.9±7.9

mg/dl, at FP were 97±17.5 mg/dl and IVB was 89±15.4 mg/dl . A statically significant correlation (p<0.001) was found between GCB and FP (r=0.94); GCB and IVB (r=0.94) and FP with IVB (r=0.97)


• Discussion;-• The American diabetic association recommends

that screening for diabetes should start at younger age and be repeated every 3 years in persons without risk factors, and earlier and more often in those with risk factors for diabetes.

• Testing at younger age or more frequently should be carried out in individuals who are (diabetic care 1997)

a)Obeseb)1st degree relative with diabetesc) Members of high-risk ethnic population,d)Gestational diabetese)Hypertensionf) HDL cholesterol level≤35mg/dl and triglyceride level ≥250mg/dl

g) Previous testing impaired fasting or impaired glucose tolerance


• The primary methods used to diagnose diabetes mellitus and monitor blood glucose levels have traditionally been fasting blood glucose, a combination of fasting blood glucose and 2-hour test after glucose loading (loe H DIABETIC CARE 1993)

• These test require fasting by the patient, tends to be highly dependent on patient compliance, result usually will only be available at subsequent visit( 2nd appointment)– Thus one more appointment is usually needed to

assess the glycemic status and make necessary therapeutic decisions.

– Also information from a single laboratory test may not reflect patients current blood glucose status.

– So monitoring their blood glucose during the office visit may be a better alternative


• Glucose monitors are of help to the clinician to assess blood glucose levels at the chairside. (Fedele D 2003).

• So it may be more convenient for dental surgeon to obtain blood sample from the gingival site.

• Stein and Nebbia 1969) were the 1st to describe a chair-side method of diabetic screening with gingival blood; they transferred blood onto test strip by wiping blood directly from hemorrhagic gingival tissue .


• Tsutsui et al 1985; reported the rubbing of blood onto the test strip from a blood –laden dental curette.– Rubbing or direct wiping of intra-oral blood

on the test strip will not produce a uniformly timed reaction and may damage the strip.

– Also there is contamination by saliva and oral debris (parker RC 1993).


• To over-come these errors, Parker et al used a glucometer, which is self-timing and requires no wiping, and used plastic pipette for collection of blood.

• Beikler et al JCP 2002; directly used test strip of glucometer to collect blood sample from gingiva.

• The glucometer used is a self-timing, 3rd generation monitor and is approved by Federation dentaire internationale (FDI) for off-finger testing.


– It requires very low amount of blood (1μl),

– Allowing to perform the analysis even in cases with very mild gingival inflammation.

– The meter is plasma calibrated ,thus allowing direct comparison of glucometer values with laboratory- derived values

– So there is no need of for calibibretion to whole blood glucose as reported early( parker RC JP 1993)


• The correlation between gingival and finger-stick capillary blood was r=0.996, p<0.001 in both diabetics and controls

• The correlation between gingival and laboratory blood glucose values was r=0.996, p<0.001 in both diabetics and controls .


• Conclusion• Following conclusions are drawn from this

study;– Glucometer teste is reliable for chair-side

assessment of glucose with gingival capillary blood from gingival sulcus , as compared with laboratory methods.

– Technique is safe, easy to perform, repeatable, comfortable for patient, cost effective, and help in increasing the frequency of diabetes screening in dental office.

– High number (11%) of detecting previously undiagnosed diabetes in periodontal patients signifies the value of having glucometer readily available in the clinics


• Although the exact physiologic pathways have not been fully delineated, obesity may increase insulin resistance by causing elevated production of TNF-a and IL-6 and decreased production of adiponectin.9,134 TNF-a can induce insulin resistance at the receptor level by preventing autophosphorylation of the insulin receptor and suppressing second messenger signaling through the inhibition of the enzyme tyrosine kinase.131 Infusion of TNF-a in healthy humans directly induces insulin resistance in skeletal muscle and reduces glucose uptake and use.135 Blocking TNF-a with pharmacologic agents has been shown to reduce seruminsulin levels and improve insulin sensitivity in some subjects136 but not in others.137 Adiponectin antagonizes many of the effects of TNF-a and improves insulin sensitivity 138 As body mass increases, adiponectin production decreases; thus, obesity results in elevatedTNF-a levels and decreased adiponectic levels, both of which result in insulin resistance.138 IL-6 stimulates TNF-a production; therefore, increased production of IL-6 from adipocytes in obese individuals causes elevated TNF-a production, which may further exacerbate insulin resistance. The increased production of TNF-a and IL-6 also stimulates greater hepatic CRP production, which may also increase insulin resistance.9,139 Multiple mechanisms are involved in regulation of insulin sensitivity and resistance, including

• One theory is that increased intracellular glucose leads to the formation of advanced glycosylation end products (AGEs), which bind to a cell surface receptor, via the nonenzymatic glycosylation of intra- and extracellular proteins. Nonenzymatic glycosylation results from the interaction of glucose with amino groups on proteins. AGEs have been shown to cross-link proteins (e.g., collagen, extracellular matrix proteins), accelerate atherosclerosis, promote glomerular dysfunction, reduce nitric oxide synthesis, induce endothelial dysfunction, and alter extracellular matrix composition and structure. The serum level of AGEs correlates with the level of glycemia, and these products accumulate as the glomerular filtration rate (GFR) declines.

• A second theory is based on the observation that hyperglycemia increases glucose metabolism via the sorbitol pathway. Intracellular glucose is predominantly metabolized by phosphorylation and subsequent glycolysis, but when increased, some glucose is converted to sorbitol by the enzyme aldose reductase. Increased sorbitol concentration alters redox potential, increases cellular osmolality, generates reactive oxygen species, and likely leads to other types of cellular dysfunction. However, testing of this theory in humans, using aldose reductase inhibitors, has not demonstrated significant beneficial effects on clinical endpoints of retinopathy, neuropathy, or nephropathy.

• A third hypothesis proposes that hyperglycemia increases the formation of diacylglycerol leading to activation of protein kinase C (PKC). Among other actions, PKC alters the transcription of genes for fibronectin, type IV collagen, contractile proteins, and extracellular matrix proteins in endothelial cells and neurons. Inhibitors of PKC are being studied in clinical trials.

• A fourth theory proposes that hyperglycemia increases the flux through the hexosamine pathway, which generates fructose-6-phosphate, a substrate for O-linked glycosylation and proteoglycan production. The hexosamine pathway may alter function by glycosylation of proteins such as endothelial nitric oxide synthase or by changes in gene expression of transforming growth factor (TGF-) or plasminogen activator inhibitor-1 (PAI-1).

Diabetes and periodontics

Health & Medicine

Transcript of Diabetes and periodontics