{"id":4422489,"date":"2025-01-11T21:16:16","date_gmt":"2025-01-12T03:16:16","guid":{"rendered":"https:\/\/myendoconsult.com\/learn\/topics\/type-2-diabetes\/"},"modified":"2025-01-12T12:20:45","modified_gmt":"2025-01-12T18:20:45","slug":"type-2-diabetes","status":"publish","type":"oen_topic","link":"https:\/\/myendoconsult.com\/learn\/topics\/type-2-diabetes\/","title":{"rendered":"Type 2 Diabetes"},"content":{"rendered":"\n<h2 class=\"wp-block-heading\">TYPE 2 DIABETES MELLITUS<\/h2>\n\n\n\n<h3 class=\"wp-block-heading\">Diagnostic Criteria for Diabetes Mellitus<\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Hyperglycemia symptoms:<\/strong> polyuria, polydipsia, weight loss.<\/li>\n\n\n\n<li><strong>Fasting plasma glucose \u2265126 mg\/dL<\/strong> on more than one occasion, or<\/li>\n\n\n\n<li><strong>Random plasma glucose \u2265200 mg\/dL<\/strong> (confirmed on another occasion), or<\/li>\n\n\n\n<li><strong>Impaired fasting glucose<\/strong> if fasting glucose is 100\u2013125 mg\/dL,<\/li>\n\n\n\n<li><strong>Impaired glucose tolerance<\/strong> if the 2-hour post\u201375-g glucose load is 140\u2013199 mg\/dL.<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\">Overview<\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Three general types<\/strong>: Type 1, Type 2, Gestational.<\/li>\n\n\n\n<li><strong>Type 2<\/strong>: &gt;90% of all diabetes cases.<\/li>\n\n\n\n<li><strong>Pathophysiology<\/strong>: Relative insulin deficiency + <a href=\"https:\/\/myendoconsult.com\/learn\/homa-ir-calculator\/\" data-wpil-monitor-id=\"235\">insulin resistance<\/a>. Most are overweight\/obese, typically diagnosed &gt;30 years of age.<\/li>\n<\/ul>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h2 class=\"wp-block-heading\">ETIOLOGY &amp; PATHOGENESIS<\/h2>\n\n\n\n<h3 class=\"wp-block-heading\">Insulin Resistance &amp; Genetic Factors<\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Insulin resistance<\/strong>: Linked to polygenic factors, obesity (especially abdominal visceral fat), sedentary lifestyle, and aging.<\/li>\n\n\n\n<li><strong>Family history<\/strong>: ~40% have \u22651 diabetic parent; <strong>concordance in identical twins ~90%<\/strong>.<\/li>\n\n\n\n<li><strong>Genetics<\/strong>: Several common polymorphisms \u2192 increased T2DM risk.<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\">Defective \u03b2-Cell Secretion<\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Inadequate \u03b2-cell insulin secretion<\/strong> relative to glucose levels.<\/li>\n\n\n\n<li><strong>Hyperglycemia<\/strong> magnifies insulin resistance and \u03b2-cell dysfunction.<\/li>\n\n\n\n<li><strong>\u03b2-cell mass decreases<\/strong> via increased apoptosis.<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\">Obesity &amp; Metabolic Syndrome<\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>80% of T2DM (in Western populations)<\/strong> are obese (BMI &gt;30 kg\/m\u00b2).<\/li>\n\n\n\n<li><strong>~30%<\/strong> of Japanese\/Chinese T2DM are obese.<\/li>\n\n\n\n<li><strong>Abdominal\/visceral obesity<\/strong> \u2192 insulin resistance \u2192 hyperglycemia \u2192 hyperinsulinemia (still insufficient).<\/li>\n\n\n\n<li><em>Metabolic syndrome:<\/em> central obesity, hyperglycemia, hyperinsulinemia, dyslipidemia, hypertension.<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\">Secondary Causes of Diabetes<\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Diffuse pancreatic damage<\/strong>: pancreatitis, trauma, carcinoma, hemochromatosis, partial pancreatectomy.<\/li>\n\n\n\n<li><strong>Excess counterregulatory hormones<\/strong>:\n<ul class=\"wp-block-list\">\n<li><em>Pheochromocytoma:<\/em> catecholamines<\/li>\n\n\n\n<li><em>Acromegaly:<\/em> growth hormone<\/li>\n\n\n\n<li><em>Glucagonoma:<\/em> glucagon<\/li>\n\n\n\n<li><em>Cushing syndrome:<\/em> glucocorticoids<\/li>\n\n\n\n<li><em>Thyrotoxicosis:<\/em> thyroid hormone<\/li>\n\n\n\n<li><em>Somatostatinoma:<\/em> somatostatin<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li>Hyperglycemia usually resolves if the underlying disorder is treated.<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\">Maturity-Onset Diabetes of the Young (MODY)<\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>5%<\/strong> of T2DM have <em>monogenic<\/em> disorders of \u03b2-cell function.<\/li>\n\n\n\n<li><strong>Typically not obese<\/strong>, onset in late childhood or young adulthood.<\/li>\n\n\n\n<li><strong>6 forms<\/strong> (autosomal dominant):\n<ol class=\"wp-block-list\">\n<li><strong>MODY 2<\/strong>: Mutation in glucokinase gene \u2192 defective glucose sensing.<\/li>\n\n\n\n<li><strong>MODY 1 &amp; 3<\/strong>: Mutations in transcription factors <em>HNF-4\u03b1<\/em> (MODY 1) or <em>HNF-1\u03b1<\/em> (MODY 3).<\/li>\n\n\n\n<li><strong>MODY 4<\/strong>: Mutation in <em>IPF-1<\/em> (insulin promoter factor-1).<\/li>\n\n\n\n<li><strong>MODY 5<\/strong>: Mutation in <em>HNF-1\u03b2<\/em>.<\/li>\n\n\n\n<li><strong>MODY 6<\/strong>: Mutation in <em>neuroD1<\/em> transcription factor.<\/li>\n<\/ol>\n<\/li>\n<\/ul>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h2 class=\"wp-block-heading\">TREATMENT OF TYPE 2 DIABETES MELLITUS<\/h2>\n\n\n\n<h3 class=\"wp-block-heading\">Goals for Glycemic Control<\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>HbA1c &lt;7%<\/strong> (ideal if &lt;6% without causing severe hypoglycemia).<\/li>\n\n\n\n<li><strong>Fasting\/premeal glucose 70\u2013130 mg\/dL<\/strong>,<\/li>\n\n\n\n<li><strong>2-hr postprandial &lt;180 mg\/dL<\/strong>.<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\">Nonpharmacologic Therapy<\/h3>\n\n\n\n<ol class=\"wp-block-list\">\n<li><strong>Lifestyle modifications<\/strong>:\n<ul class=\"wp-block-list\">\n<li>Balanced nutrition &amp; caloric management<\/li>\n\n\n\n<li>Regular isotonic exercise<\/li>\n\n\n\n<li>Weight reduction<\/li>\n\n\n\n<li>Behavior modification<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Diabetes education<\/strong>: emphasis on patient <em>self-management<\/em>.<\/li>\n\n\n\n<li><strong>Self-monitoring of blood glucose (SMBG)<\/strong>.<\/li>\n<\/ol>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h2 class=\"wp-block-heading\">PHARMACOTHERAPY OPTIONS<\/h2>\n\n\n\n<h3 class=\"wp-block-heading\">1. Biguanides (Metformin)<\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Mechanism<\/strong>: activates AMP-activated protein kinase, <strong>\u2193 hepatic <a href=\"https:\/\/myendoconsult.com\/learn\/gluconeogenesis\/\" data-wpil-monitor-id=\"236\">gluconeogenesis<\/a><\/strong>.<\/li>\n\n\n\n<li><strong>No hypoglycemia<\/strong> risk.<\/li>\n\n\n\n<li><strong>GI side effects<\/strong> common (nausea, diarrhea).<\/li>\n\n\n\n<li><strong>Contraindications<\/strong>: renal insufficiency (lactic acidosis risk).<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\">2. Thiazolidinediones (TZDs)<\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Drugs<\/strong>: pioglitazone, rosiglitazone.<\/li>\n\n\n\n<li><strong>Mechanism<\/strong>: Peroxisome proliferator-activated receptor (PPAR-\u03b3) modulation \u2192 <strong>\u2193 peripheral insulin resistance<\/strong>, <strong>\u2193 serum triglycerides<\/strong>.<\/li>\n\n\n\n<li><strong>Side effects<\/strong>: weight gain (subQ fat), fluid retention \u2192 edema, possible heart failure exacerbation.<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\">3. Insulin Secretagogues<\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Sulfonylureas<\/strong>: (1st gen: acetohexamide, chlorpropamide, tolbutamide; 2nd gen: glipizide, glyburide, glimepiride)\n<ul class=\"wp-block-list\">\n<li><strong>Mechanism<\/strong>: stimulate insulin release via SUR2 (K+ channel) on \u03b2-cells.<\/li>\n\n\n\n<li><strong>Side effects<\/strong>: hypoglycemia.<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Meglitinides<\/strong>: repaglinide, nateglinide\n<ul class=\"wp-block-list\">\n<li>Short half-life, taken premeal, also bind SUR1 site \u2192 insulin release.<\/li>\n\n\n\n<li><strong>Side effects<\/strong>: hypoglycemia.<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\">4. \u03b1-Glucosidase Inhibitors (AGIs)<\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Drugs<\/strong>: acarbose, miglitol.<\/li>\n\n\n\n<li><strong>Mechanism<\/strong>: inhibit final carbohydrate digestion in small intestine \u2192 <strong>delay CHO absorption<\/strong> \u2192 lower postprandial glucose.<\/li>\n\n\n\n<li><strong>Side effects<\/strong>: flatulence, diarrhea.<\/li>\n\n\n\n<li><strong>Must be taken<\/strong> at meal onset.<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\">5. Incretin-Related Agents<\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>GLP-1<\/strong> (glucagon-like peptide 1):\n<ul class=\"wp-block-list\">\n<li>Increases insulin secretion, slows gastric emptying, reduces appetite.<\/li>\n\n\n\n<li>Rapidly degraded by DPP-4.<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Exenatide<\/strong>: GLP-1 receptor agonist, resistant to DPP-4; subQ twice daily. \u2192 <em>Nausea<\/em> common.<\/li>\n\n\n\n<li><strong>Liraglutide<\/strong>: once-daily subQ DPP-4\u2013resistant GLP-1 analogue.<\/li>\n\n\n\n<li><strong>DPP-4 Inhibitors<\/strong>: sitagliptin, saxagliptin, vildagliptin \u2192 mild \u2191 endogenous GLP-1\/GIP.<\/li>\n<\/ul>\n\n\n\n<figure class=\"wp-block-image size-full\"><img loading=\"lazy\" decoding=\"async\" width=\"3300\" height=\"2400\" src=\"https:\/\/myendoconsult.com\/learn\/wp-content\/uploads\/GLP-1-mechanism-of-action.png\" alt=\"Mechanism of action of GLP-1 agonists\" class=\"wp-image-4422726\" srcset=\"https:\/\/myendoconsult.com\/learn\/wp-content\/uploads\/GLP-1-mechanism-of-action.png 3300w, https:\/\/myendoconsult.com\/learn\/wp-content\/uploads\/GLP-1-mechanism-of-action-300x218.png 300w, https:\/\/myendoconsult.com\/learn\/wp-content\/uploads\/GLP-1-mechanism-of-action-768x559.png 768w, https:\/\/myendoconsult.com\/learn\/wp-content\/uploads\/GLP-1-mechanism-of-action-1536x1117.png 1536w, https:\/\/myendoconsult.com\/learn\/wp-content\/uploads\/GLP-1-mechanism-of-action-2048x1489.png 2048w\" sizes=\"auto, (max-width: 3300px) 100vw, 3300px\" \/><figcaption class=\"wp-element-caption\">Mechanism of action of GLP-1 agonists<\/figcaption><\/figure>\n\n\n\n<h3 class=\"wp-block-heading\">6. Amylin Analogues<\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Pramlintide<\/strong>: co-secreted normally with insulin, subQ at meals.<\/li>\n\n\n\n<li><strong>Mechanism<\/strong>: slows gastric emptying, reduces appetite, suppresses glucagon.<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\">7. Insulin<\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Exogenous insulin<\/strong> to supplement endogenous secretion.<\/li>\n\n\n\n<li><strong>Types<\/strong>:\n<ul class=\"wp-block-list\">\n<li>Rapid-acting (lispro, aspart, glulisine),<\/li>\n\n\n\n<li>Short-acting (regular),<\/li>\n\n\n\n<li>Intermediate (NPH),<\/li>\n\n\n\n<li>Long-acting (glargine, detemir).<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Side effects<\/strong>: hypoglycemia, weight gain.<\/li>\n<\/ul>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h2 class=\"wp-block-heading\">INITIAL THERAPEUTIC APPROACH<\/h2>\n\n\n\n<ol class=\"wp-block-list\">\n<li><strong>Metformin + Diet + Exercise<\/strong> typically first-line.<\/li>\n\n\n\n<li><strong>More than one agent<\/strong> often needed if fasting glucose &gt;250 mg\/dL at presentation.\n<ul class=\"wp-block-list\">\n<li>e.g., Metformin plus a sulfonylurea or insulin.<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Postprandial hyperglycemia<\/strong> can be targeted with:\n<ul class=\"wp-block-list\">\n<li>AGIs,<\/li>\n\n\n\n<li>Rapid-acting insulin,<\/li>\n\n\n\n<li>Semaglutide, Tirzepatide (<a data-wpil-monitor-id=\"237\" href=\"https:\/\/myendoconsult.com\/learn\/mechanism-of-action-of-glp-1-agonists\/\">GLP-1 agonist<\/a>).<\/li>\n<\/ul>\n<\/li>\n<\/ol>\n\n\n\n<p><a href=\"https:\/\/myendoconsult.com\/learn\/medications-for-diabetes\/\" data-type=\"link\" data-id=\"https:\/\/myendoconsult.com\/learn\/medications-for-diabetes\/\">Click here to learn more about diabetes treatments.<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"<p>TYPE 2 DIABETES MELLITUS Diagnostic Criteria for Diabetes Mellitus Overview ETIOLOGY &amp; PATHOGENESIS Insulin Resistance &amp; Genetic Factors Defective \u03b2-Cell Secretion Obesity &amp; Metabolic Syndrome Secondary Causes of Diabetes Maturity-Onset Diabetes of the Young (MODY) TREATMENT OF TYPE 2 DIABETES MELLITUS Goals for Glycemic Control Nonpharmacologic Therapy PHARMACOTHERAPY OPTIONS 1. Biguanides (Metformin) 2. Thiazolidinediones (TZDs) [&hellip;]<\/p>\n","protected":false},"featured_media":0,"template":"","oen_topic_chapter":[686],"class_list":["post-4422489","oen_topic","type-oen_topic","status-publish","hentry","oen_topic_chapter-the-pancreas","post-wrapper","thrv_wrapper"],"_links":{"self":[{"href":"https:\/\/myendoconsult.com\/learn\/wp-json\/wp\/v2\/oen_topic\/4422489","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/myendoconsult.com\/learn\/wp-json\/wp\/v2\/oen_topic"}],"about":[{"href":"https:\/\/myendoconsult.com\/learn\/wp-json\/wp\/v2\/types\/oen_topic"}],"version-history":[{"count":8,"href":"https:\/\/myendoconsult.com\/learn\/wp-json\/wp\/v2\/oen_topic\/4422489\/revisions"}],"predecessor-version":[{"id":4422740,"href":"https:\/\/myendoconsult.com\/learn\/wp-json\/wp\/v2\/oen_topic\/4422489\/revisions\/4422740"}],"wp:attachment":[{"href":"https:\/\/myendoconsult.com\/learn\/wp-json\/wp\/v2\/media?parent=4422489"}],"wp:term":[{"taxonomy":"oen_topic_chapter","embeddable":true,"href":"https:\/\/myendoconsult.com\/learn\/wp-json\/wp\/v2\/oen_topic_chapter?post=4422489"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}