{"id":4422484,"date":"2025-01-11T21:05:59","date_gmt":"2025-01-12T03:05:59","guid":{"rendered":"https:\/\/myendoconsult.com\/learn\/topics\/type-1-diabetes\/"},"modified":"2025-01-12T12:18:28","modified_gmt":"2025-01-12T18:18:28","slug":"type-1-diabetes","status":"publish","type":"oen_topic","link":"https:\/\/myendoconsult.com\/learn\/topics\/type-1-diabetes\/","title":{"rendered":"Type 1 Diabetes"},"content":{"rendered":"\n<h2 class=\"wp-block-heading\">TYPE 1 DIABETES MELLITUS<\/h2>\n\n\n\n<h3 class=\"wp-block-heading\">Diagnosis<\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Definition:<\/strong> Diabetes mellitus is established when:\n<ol class=\"wp-block-list\">\n<li><strong>Typical hyperglycemia symptoms<\/strong> (polyuria, polydipsia, weight loss)<\/li>\n\n\n\n<li><strong>Fasting plasma glucose \u2265126 mg\/dL<\/strong> OR <strong>Random plasma glucose \u2265200 mg\/dL<\/strong> (confirmed on another occasion)<\/li>\n<\/ol>\n<\/li>\n\n\n\n<li><strong>Three general types of diabetes mellitus:<\/strong>\n<ol class=\"wp-block-list\">\n<li>Type 1 DM<\/li>\n\n\n\n<li>Type 2 DM <\/li>\n\n\n\n<li>Gestational DM <\/li>\n<\/ol>\n<\/li>\n\n\n\n<li><strong>Prevalence:<\/strong> Type 1 DM &lt;10% of all diabetes cases.<\/li>\n\n\n\n<li><strong>Pathophysiology:<\/strong> Pancreatic \u03b2-cell destruction \u2192 <strong>absolute insulin deficiency<\/strong> \u2192 if untreated, fatal catabolic disorder. All patients require <strong>insulin replacement therapy<\/strong>.<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\">Incidence and Risk Factors<\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Geographic variation<\/strong>:\n<ul class=\"wp-block-list\">\n<li>Highest incidence in northern Europe (~30\/100,000 persons\/year).<\/li>\n\n\n\n<li>Lowest in China (~1\/100,000 persons\/year).<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Typical onset:<\/strong> children\/young adults (though can occur at any age).<\/li>\n\n\n\n<li><strong>Family risk:<\/strong>\n<ul class=\"wp-block-list\">\n<li>Offspring of diabetic mother: 3% risk.<\/li>\n\n\n\n<li>Offspring of diabetic father: 6% risk.<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Environment + genetics:<\/strong> Only ~50% of identical twins both develop T1DM \u2192 environmental triggers (e.g., infections\/toxins) + genetic predisposition.<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\">Genetic Associations<\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>HLA class II<\/strong> (DQ, DR):\n<ul class=\"wp-block-list\">\n<li>95% of patients have HLA-DR3, HLA-DR4, or both (vs. ~50% in controls).<\/li>\n\n\n\n<li>Some DQ alleles (e.g., DQA1<em>0102, DQB1<\/em>0602) \u2192 decreased risk.<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Non-HLA genes:<\/strong> e.g., polymorphisms in PTPN22, promoter region of insulin gene \u2192 increased susceptibility.<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\">Autoimmune Mechanisms<\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Autoimmune basis<\/strong> in &gt;95% of type 1 cases.<\/li>\n\n\n\n<li>Loss of tolerance \u2192 immune system targets \u03b2-cell proteins with \u201cmolecular mimicry.\u201d<\/li>\n\n\n\n<li><strong>Autoantibodies<\/strong> (present in most new T1DM):\n<ul class=\"wp-block-list\">\n<li><a href=\"https:\/\/myendoconsult.com\/learn\/islet-cells-of-the-pancreas\/\" data-wpil-monitor-id=\"232\">Islet cell<\/a> antibody<\/li>\n\n\n\n<li>Anti\u2013glutamic acid decarboxylase (GAD)<\/li>\n\n\n\n<li>Anti\u2013tyrosine phosphatases (IA2)<\/li>\n\n\n\n<li>Zinc transporter<\/li>\n\n\n\n<li>Insulin autoantibody<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\">Natural History<\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Chronic autoimmune \u03b2-cell destruction<\/strong> over months\/years.<\/li>\n\n\n\n<li><strong>Latent period:<\/strong> normal glucose tolerance while \u03b2-cells are being lost.<\/li>\n\n\n\n<li><strong>Impaired glucose tolerance<\/strong> \u2192 overt diabetes when &gt;90% \u03b2-cell mass destroyed.<\/li>\n\n\n\n<li><strong>Toxic hyperglycemia<\/strong> accelerates remaining \u03b2-cell apoptosis.<\/li>\n\n\n\n<li><strong>Honeymoon period<\/strong>: short-term partial recovery after exogenous insulin started.<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\">Histopathology<\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Early: \u201chydropic\u201d changes (actually glycogen infiltration).<\/li>\n\n\n\n<li><strong>Selective \u03b2-cell destruction<\/strong>; islets show:\n<ul class=\"wp-block-list\">\n<li>Chronic inflammatory infiltrate (insulitis) with T lymphocytes (CD8&gt;CD4).<\/li>\n\n\n\n<li>Eventually islets become hyalinized, partially or completely replaced.<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\">Clinical Presentation<\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Classic hyperglycemia signs<\/strong>: polyuria, polydipsia, blurred vision (osmotic effect), weight loss.<\/li>\n\n\n\n<li><strong>Volume depletion<\/strong> \u2192 postural hypotension.<\/li>\n\n\n\n<li><strong>Hyperglycemic neurotoxicity<\/strong> \u2192 paresthesias.<\/li>\n\n\n\n<li><strong>Severe insulin deficiency<\/strong> \u2192 <a data-wpil-monitor-id=\"233\" href=\"https:\/\/myendoconsult.com\/learn\/diabetic-ketoacidosis-dka-protocol\/\">diabetic ketoacidosis<\/a> (DKA).<\/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 1 DIABETES MELLITUS<\/h2>\n\n\n\n<h3 class=\"wp-block-heading\">Importance of Tight Glycemic Control<\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Reduces risk of:\n<ul class=\"wp-block-list\">\n<li>Retinopathy<\/li>\n\n\n\n<li>Nephropathy<\/li>\n\n\n\n<li>Neuropathy<\/li>\n\n\n\n<li>Cardiovascular disease<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Glycemic goals<\/strong>:\n<ul class=\"wp-block-list\">\n<li>HbA1c &lt;7% (&lt;6% is optimal if achievable safely).<\/li>\n\n\n\n<li>Fasting\/premeal glucose 70\u2013130 mg\/dL.<\/li>\n\n\n\n<li>2-hr postprandial &lt;180 mg\/dL.<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\">Insulin Therapy<\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Absolute requirement<\/strong> for exogenous insulin.<\/li>\n\n\n\n<li><strong>Two main regimens<\/strong>:\n<ol class=\"wp-block-list\">\n<li><strong>Multiple daily injections (MDI)<\/strong><\/li>\n\n\n\n<li><strong>Continuous subcutaneous insulin infusion (CSII) (insulin pump)<\/strong><\/li>\n<\/ol>\n<\/li>\n<\/ul>\n\n\n\n<figure class=\"wp-block-image size-full is-style-default wp-duotone-unset-1\"><img loading=\"lazy\" decoding=\"async\" width=\"960\" height=\"672\" src=\"https:\/\/myendoconsult.com\/learn\/wp-content\/uploads\/DKA-infographic.png\" alt=\"\" class=\"wp-image-4421650\" srcset=\"https:\/\/myendoconsult.com\/learn\/wp-content\/uploads\/DKA-infographic.png 960w, https:\/\/myendoconsult.com\/learn\/wp-content\/uploads\/DKA-infographic-300x210.png 300w, https:\/\/myendoconsult.com\/learn\/wp-content\/uploads\/DKA-infographic-768x538.png 768w\" sizes=\"auto, (max-width: 960px) 100vw, 960px\" \/><figcaption class=\"wp-element-caption\">Management Protocol for Diabetic Ketoacidosis<\/figcaption><\/figure>\n\n\n\n<h3 class=\"wp-block-heading\">Types of Insulin<\/h3>\n\n\n\n<ol class=\"wp-block-list\">\n<li><strong>Rapid-acting analogues<\/strong> (lispro, aspart, glulisine):\n<ul class=\"wp-block-list\">\n<li>Onset ~15 minutes<\/li>\n\n\n\n<li>Peak ~1 hour<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Short-acting (regular insulin)<\/strong>:\n<ul class=\"wp-block-list\">\n<li>Onset 30\u201360 minutes<\/li>\n\n\n\n<li>Peak 2\u20134 hours<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Intermediate-acting (NPH)<\/strong>:\n<ul class=\"wp-block-list\">\n<li>Onset 1\u20133 hours<\/li>\n\n\n\n<li>Peak 6\u20138 hours<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Long-acting (glargine, detemir)<\/strong>:\n<ul class=\"wp-block-list\">\n<li>Onset ~1 hour<\/li>\n\n\n\n<li>Minimal peak<\/li>\n\n\n\n<li>Duration ~24 hours<\/li>\n<\/ul>\n<\/li>\n<\/ol>\n\n\n\n<h3 class=\"wp-block-heading\">Modifications (Analogs)<\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Rapid-acting<\/strong>:\n<ul class=\"wp-block-list\">\n<li><em>Lispro:<\/em> Invert \u03b2-28 (Lys) and \u03b2-29 (Pro)<\/li>\n\n\n\n<li><em>Aspart:<\/em> Replace \u03b2-28 (Pro) with Asp<\/li>\n\n\n\n<li><em>Glulisine:<\/em> Replace \u03b2-3 (Asn) with Lys, \u03b2-29 (Lys) with Glu<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Long-acting<\/strong>:\n<ul class=\"wp-block-list\">\n<li><em>Glargine:<\/em> Replace \u03b1-21 (Asn) with Gly + add 2 Arg to \u03b2-chain \u2192 forms microprecipitates in subQ.<\/li>\n\n\n\n<li><em>Detemir:<\/em> Remove \u03b2-30 (Thr) + attach C14 fatty acid at \u03b2-29 \u2192 prolongs absorption.<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n\n\n\n<figure class=\"wp-block-image size-full\"><img loading=\"lazy\" decoding=\"async\" width=\"3000\" height=\"2100\" src=\"https:\/\/myendoconsult.com\/learn\/wp-content\/uploads\/insulin-analog-substitutions.png\" alt=\"\" class=\"wp-image-4422721\" srcset=\"https:\/\/myendoconsult.com\/learn\/wp-content\/uploads\/insulin-analog-substitutions.png 3000w, https:\/\/myendoconsult.com\/learn\/wp-content\/uploads\/insulin-analog-substitutions-300x210.png 300w, https:\/\/myendoconsult.com\/learn\/wp-content\/uploads\/insulin-analog-substitutions-768x538.png 768w, https:\/\/myendoconsult.com\/learn\/wp-content\/uploads\/insulin-analog-substitutions-1536x1075.png 1536w, https:\/\/myendoconsult.com\/learn\/wp-content\/uploads\/insulin-analog-substitutions-2048x1434.png 2048w\" sizes=\"auto, (max-width: 3000px) 100vw, 3000px\" \/><figcaption class=\"wp-element-caption\">Analogs of insulin showing amino acid locations<\/figcaption><\/figure>\n\n\n\n<h3 class=\"wp-block-heading\">Amylin Analogues<\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Amylin<\/strong> is normally cosecreted with insulin by \u03b2-cells (deficient in T1DM).<\/li>\n\n\n\n<li><strong>Pramlintide:<\/strong> amylin analogue, subQ before meals; helps improve glycemic control by:\n<ul class=\"wp-block-list\">\n<li>Delaying gastric emptying<\/li>\n\n\n\n<li>Reducing appetite<\/li>\n\n\n\n<li>Suppressing glucagon<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\">Intensive Insulin Programs<\/h3>\n\n\n\n<ol class=\"wp-block-list\">\n<li><strong>MDI<\/strong>:\n<ul class=\"wp-block-list\">\n<li>Long-acting analog (glargine\/detemir) at bedtime for basal coverage<\/li>\n\n\n\n<li>Rapid-acting analogs before meals<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>CSII<\/strong> (Insulin pump):\n<ul class=\"wp-block-list\">\n<li>Continuous rapid-acting insulin via subQ catheter<\/li>\n\n\n\n<li>Preprogrammed <a href=\"https:\/\/myendoconsult.com\/learn\/insulin-pump-basal-rate-testing\/\" data-wpil-monitor-id=\"234\">basal rate<\/a> + patient-activated boluses premeal<\/li>\n\n\n\n<li>Adjust basal profile for circadian changes<\/li>\n<\/ul>\n<\/li>\n<\/ol>\n\n\n\n<figure class=\"wp-block-image size-full\"><img loading=\"lazy\" decoding=\"async\" width=\"3000\" height=\"1950\" src=\"https:\/\/myendoconsult.com\/learn\/wp-content\/uploads\/Insulin-Pump.png\" alt=\"insulin pump therapy\" class=\"wp-image-4422733\" srcset=\"https:\/\/myendoconsult.com\/learn\/wp-content\/uploads\/Insulin-Pump.png 3000w, https:\/\/myendoconsult.com\/learn\/wp-content\/uploads\/Insulin-Pump-300x195.png 300w, https:\/\/myendoconsult.com\/learn\/wp-content\/uploads\/Insulin-Pump-768x499.png 768w, https:\/\/myendoconsult.com\/learn\/wp-content\/uploads\/Insulin-Pump-1536x998.png 1536w, https:\/\/myendoconsult.com\/learn\/wp-content\/uploads\/Insulin-Pump-2048x1331.png 2048w\" sizes=\"auto, (max-width: 3000px) 100vw, 3000px\" \/><figcaption class=\"wp-element-caption\">Hybrid closed loop insulin delivery system (Insulin Pump Device)<\/figcaption><\/figure>\n\n\n\n<p><strong>Hypoglycemia<\/strong> is a major complication:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Risk of falls, accidents, seizures<\/li>\n\n\n\n<li>Autonomic neuropathy \u2192 \u201chypoglycemic unawareness\u201d (loss of adrenergic warning signs)<\/li>\n\n\n\n<li>Essential to have <strong>readily available carbs<\/strong> (glucose tablets) + <strong>injectable glucagon<\/strong> kit<\/li>\n<\/ul>\n","protected":false},"excerpt":{"rendered":"<p>TYPE 1 DIABETES MELLITUS Diagnosis Incidence and Risk Factors Genetic Associations Autoimmune Mechanisms Natural History Histopathology Clinical Presentation TREATMENT OF TYPE 1 DIABETES MELLITUS Importance of Tight Glycemic Control Insulin Therapy Types of Insulin Modifications (Analogs) Amylin Analogues Intensive Insulin Programs Hypoglycemia is a major complication:<\/p>\n","protected":false},"featured_media":0,"template":"","oen_topic_chapter":[686],"class_list":["post-4422484","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\/4422484","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":14,"href":"https:\/\/myendoconsult.com\/learn\/wp-json\/wp\/v2\/oen_topic\/4422484\/revisions"}],"predecessor-version":[{"id":4422735,"href":"https:\/\/myendoconsult.com\/learn\/wp-json\/wp\/v2\/oen_topic\/4422484\/revisions\/4422735"}],"wp:attachment":[{"href":"https:\/\/myendoconsult.com\/learn\/wp-json\/wp\/v2\/media?parent=4422484"}],"wp:term":[{"taxonomy":"oen_topic_chapter","embeddable":true,"href":"https:\/\/myendoconsult.com\/learn\/wp-json\/wp\/v2\/oen_topic_chapter?post=4422484"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}