Diabetes mellitus is a disease characterized by insufficient insulin levels or responsiveness of tissues to insulin, resulting in abnormal plasma glucose levels. Dyslipidemia, or imbalances in circulating lipids and lipoproteins, is also commonly associated with diabetes. The major symptoms of diabetes mellitus include hyperglycemia, polyuria, polydipsia, polyphagia, muscle wasting, electrolyte depletion, and ketoacidosis in type 1 diabetes mellitus (T1DM). In order to diagnose diabetes, fasting plasma glucose levels should be below 110 mg/dL after at least 8 hours without caloric intake. Impaired glucose control is indicated if fasting plasma glucose levels range between 110 and 126 mg/dL, while a diagnosis of diabetes is made if fasting plasma glucose exceeds 126 mg/dL on 2 successive days. Another diagnostic approach is the oral glucose tolerance test, where a patient is given a bolus of glucose (typically 75g) orally after overnight fasting, and blood glucose levels are measured at 2 hours. A 2-hour plasma glucose concentration greater than 200 mg/dL on 2 consecutive days is sufficient to diagnose diabetes. Additionally, a diagnosis of diabetes is also made if a patient presents symptoms associated with diabetes and has a non-fasting plasma glucose level greater than 200 mg/dL. Diabetes mellitus is classified into two types: type 1 (T1DM) and type 2 (T2DM). T2DM is the more common form, accounting for 90% of diagnosed cases. However, T2DM often remains undiagnosed in a significant percentage of patients for several years. This form of diabetes is frequently associated with visceral obesity and lack of exercise, which has led to an epidemic of obesity-related T2DM worldwide. The development of T2DM in individuals is usually influenced by multiple causes that are associated with defects in the ability of target organs to respond to insulin (insulin resistance) and some degree of beta cell deficiency. Insulin sensitivity can be compromised at the level of the InsR or at the level of post-receptor signaling. T2DM is believed to result from insulin resistance followed by reactive hyperinsulinemia, but ultimately leads to relative hypoinsulinemia and beta cell failure.
Diabetes mellitus isadiseaseinwhichinsulinlevelsorresponsivenessoftissuestoinsulin(orboth)isinsufficienttomaintainnormallevelsofplasmaglucose.Althoughthediagnosisofdiabetesisbasedprimarilyonplasmaglucose,diabetesalsopromotesimbalancesincirculatinglevelsoflipidsandlipoproteins(i.e.,dyslipidemia).Majorsymptomsofdiabetesmellitusincludehyperglycemia,polyuria,polydipsia,polyphagia,musclewasting,electrolytedepletion,andketoacidosis(inT1DM).Withnormalfasting(i.e.,nocaloricintakeforatleast8hours),plasmaglucoselevelsshouldbebelow110mg/dL.Apatientisconsideredtohaveimpairedglucosecontroliffastingplasmaglucoselevelsarebetween110and126mg/dL,andthediagnosisofdiabetesismadeiffastingplasmaglucoseexceeds126mg/dLon2successivedays.Anotherapproachtothediagnosisofdiabetesistheoralglucosetolerancetest.Afterovernightfastingthepatientisgivenabolusofglucose(usually75g)orally,andbloodglucoselevelsaremeasuredat2hours.A2-hourplasmaglucoseconcentrationgreaterthan200mg/dLon2consecutivedaysissufficienttomakethediagnosisofdiabetes.Thediagnosisofdiabetesisalsoindicatedifthepatienthassymptomsassociatedwithdiabetesandhasanonfastingplasmaglucoselevelgreaterthan200mg/dL.
Diabetesmellitusiscurrentlyclassifiedastype 1 (T1DM) ortype 2 (T2DM). T2DMisbyfarthemorecommonformandaccountsfor90%ofdiagnosedcases.However,T2DMisusuallyaprogressivediseasethatremainsundiagnosedinasignificantpercentageofpatientsforseveralyears.T2DMisoftenassociatedwithvisceralobesityandlackofexercise—indeed,obesity-relatedT2DMisreachingepidemicproportionsworldwide.UsuallytherearemultiplecausesforthedevelopmentofT2DMinagivenindividualthatareassociatedwithdefectsintheabilityoftargetorganstorespondtoinsulin(i.e.,insulin resistance),alongwithsomedegreeofbeta cell deficiency. InsulinsensitivitycanbecompromisedattheleveloftheInsRoratthelevelofpostreceptorsignaling.T2DMappearstobetheconsequenceofinsulinresistance,followedbyreactivehyperinsulinemia,butultimatelybyrelative hypoinsulinemia (i.e.,inadequatereleaseofinsulintocompensatefortheend-organresistance)andbeta cell failure.