out periodontitis. ^{23, 27, 28} Periodontal treatment decreased creatic insulin production in an effort to force glucose into serum levels of IL- 6 and CRP in intervention trials, and the cells. ³² This insulin resistance represents the major the decrease was greatest in patients who had significant underlying pathophysiologic abnormality of type 2 DM clinical reductions in periodontal inflammation. ²⁹ Those and differentiates it from type 1 DM. In type 1 DM, insulin who showed little clinical improvement in periodontal resistance plays much less of a role in the pathogenesis parameters after treatment also showed little change in of disease, but insulin resistance associated with illness serum acute-phase reactant levels. Thus, localized peri- or infection can make type 1 DM more difficult to control odontal inflammation has the potential to perpetuate a as well. Even after the resolution of the acute illness, tis-chronic systemic inflammatory state, which may impact sues may remain resistant to insulin for many weeks or other inflammation-related conditions in the body, such months, further exacerbating the diabetic condition. ^{33, 34} as DM. With persistent infection and after oral glucose intake,

hyperglycemia and hyperinsulinemia develop. These are

Diabetes Mellitus and Insulin Resistance the hallmarks of insulin resistance and are associated
Diabetes mellitus comprises a clinically and genetically with the many systemic complications of diabetes, includ-
diverse group of hormonal diseases that are character- ing blindness, kidney failure, myocardial infarction (MI),
ized by alterations in carbohydrate, protein, and lipid stroke, infection, and the need for limb amputation. ³⁵
metabolism, the primary manifestation being abnormally
high blood-glucose levels. ³⁰ This hyperglycemia is attrib- As noted earlier, the increase in type 2 DM incidence par-
uted to a lack of insulin secretion by the pancreas, a re- allels an increase in obesity, with more than 30% of U.S.
duction in insulin activity, or a combination of both. The adults being obese. ³⁶ Obesity, defined as body mass index
resultant elevated systemic glucose levels affect almost (BMI) > 30 kg/m², is a major risk factor for both type 2 DM
all organs in the body, including the cardiovascular sys- and cardiovascular disease (CVD). ³⁷ Adipocytes are highly
tem, eyes, nerves, kidneys, and the periodontium. metabolically active cells and produce various substances
important in energy regulation in the body. These include

Type 1 DM comprises about 5%-10% of all cases and usu- cytokines such as TNF-α, which contribute to insulin really has an early age of onset. Type 1 DM results from sistance by inhibiting cell surface insulin receptor action autoimmune destruction of the β-cells of the pancreas, through the suppression of tyrosine-kinase phosphoryla-which renders the patient incapable of producing endog- tion of insulin receptor substrate- 1 (IRS- 1), thereby block-enous insulin. ³¹ Without adequate insulin to allow glucose ing the translocation of glucose-transporting proteins. ^{38, 39} from the bloodstream to enter cells, cellular starvation Additionally, elevated serum levels of free fatty acids pro-takes place at the same time glucose levels build up in the duced by adipocytes may contribute to insulin resistance bloodstream. Fat then is broken down through lipolysis as by lowering glucose uptake, synthesis of glycogen, and the body seeks a secondary energy source. Large amounts glycolysis, and by raising hepatic glucose production. ⁴⁰ of free fatty acids accumulate in the bloodstream and are With weight loss, insulin resistance often improves but converted into ketones, which may result in ketoacidosis, usually does not return to normal. a potentially life-threatening condition.

Gestational diabetes occurs in approximately 4% of all

Type 2 DM, the most common form, results from altered pregnancies in the U.S., ⁴¹ usually with onset in the third insulin action on cells. Unlike patients with type 1 DM, pa- trimester. Similar to type 2 DM, gestational diabetes is tients with type 2 DM retain the ability to produce some associated with insulin resistance. Proper diagnosis and insulin, although this production decreases with disease management significantly improve pregnancy outcomes. duration. Diabetic ketoacidosis is uncommon in type 2 After delivery, most patients return to a normoglycemic DM because enough endogenous insulin is produced to state; however, women with a history of gestational dia-keep ketone formation low. In patients with type 2 DM, betes have a significantly increased chance of developing increasing cellular energy demands cause insulin recep- type 2 DM later in life. tors to be displayed on the surface of nearly all cells ( except brain cells), which facilitates glucose loading from Insulin resistance has been implicated as a key factor the bloodstream into the cells. However, certain events, in the development of the metabolic syndrome, a condi-such as acute bacterial or viral infections, can cause cells tion that may effect at least 1 in 5 overweight people. ⁴² to become insulin-resistant, resulting in increased pan- Patients with this syndrome, also known as the “insulin