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Key Points

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  • Disease summary:

    • Diabetes is a chronic metabolic disorder characterized by high levels of blood glucose that may lead to micro- and macrovascular complications if not controlled effectively. Type 2 diabetes mellitus (T2DM), which is characterized by defects in insulin secretion and insulin action, is the most common form of diabetes.

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  • Differential diagnosis:

    • Secondary causes of hyperglycemia should be considered. The classic differential diagnosis includes type 1 diabetes, maturity-onset diabetes of the young (MODY), pancreatic dysfunction, gestational diabetes, and other causes of obesity and insulin resistance, such as Cushing syndrome, acromegaly, polycystic ovarian disease, and drug-induced hyperglycemia (glucocorticoids).

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  • Screening:

    • Routine screening for T2DM should be performed in overweight patients, including children, possessing additional risk factors at least in every 3 years. In the absence of risk factors, testing for diabetes should begin at age 45.

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  • Hereditary basis:

    • T2DM is a polygenic disorder with 40% to 60% heritability. About 2% to 3% of diabetes is inherited as monogenic forms of diabetes; the most common monogenic forms are referred as MODY to distinguish them from type 1 and type 2 diabetes.

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  • Family history and twin studies:

    • The risk of developing T2DM in siblings of patients with T2DM is up to three times higher than that of the general population. Monozygotic twins have a 60% or higher long-term concordance rate for diabetes, much higher than the 25% concordance rate observed for T1DM in monozygotic twins.

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  • Environmental factors:

    • Obesity, sedentary lifestyle

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  • Genome-wide associations:

    • At least 37 variants have been associated with T2DM. All have small effect sizes and the known risk alleles, even collectively, do a poor job at predicting the future development of diabetes.

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  • Pharmacogenetics:

    • Identifying genetic variants that predict response to the blood glucose-lowering effects of antidiabetic medications is of great interest because of the high prevalence of diabetes and the large number of patients prescribed such medications. At present, there is insufficient basis for prescribing medication based on genotype.

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Diagnostic Criteria and Clinical Characteristics

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Diagnostic Criteria for Diabetes

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One of the following

  1. Fasting plasma glucose (FPG) greater than or equal to 126 mg/dL

  2. Two-hour plasma glucose greater than or equal to 200 mg/dL during an oral glucose tolerance test (OGTT).

  3. In a patient with classic symptoms of hyperglycemia or hyperglycemic crisis, a random plasma glucose greater than or equal to 200 mg/dL

  4. Hemoglobin A1c greater than or equal to 6.5%

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Diagnostic Criteria for Prediabetes

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One of the following

  1. FPG between 100 to 125 mg/dL

  2. Two-hour plasma glucose of 140 to 199 mg/dL during a 75-g OGTT

  3. Hemoglobin A1c of 5.7% to 6.4%

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Clinical Characteristics

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Diabetes is characterized by high levels of plasma glucose. T2DM, which is due to defects in insulin sensitivity and/or insulin secretion, ...

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