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Diabetes Mellitus CMS200 Week 3 Dr. Jeanny Kim, ND Learning Outcomes Interpret the essentials of diagnosing, classifying, and managing Type 1 and Type 2 diabetes, including their differences, common symptoms, and causes. Evaluate the risk factors, epidemiologic considerations, and screeni...

Diabetes Mellitus CMS200 Week 3 Dr. Jeanny Kim, ND Learning Outcomes Interpret the essentials of diagnosing, classifying, and managing Type 1 and Type 2 diabetes, including their differences, common symptoms, and causes. Evaluate the risk factors, epidemiologic considerations, and screening recommendations for various types of diabetes, including gestational diabetes and diabetes in children, adolescents, and geriatric patients. Analyze the role of plasma glucose levels, HbA1c levels, oral glucose tolerance test, and other diagnostic tests in diagnosing and monitoring diabetes mellitus, as well as their limitations and when additional testing may be necessary. Learning Outcomes Investigate the metabolic syndrome, insulin resistance, and the genetic and hereditary profiles of diabetes. Appraise the clinical findings, complications, and associated conditions of diabetes, such as diabetic nephropathy, neuropathy, retinopathy, foot ulcers, and hyperosmolar hyperglycemic state (HHS). Evaluate the importance of patient education, engagement, and ongoing monitoring of other organ systems in the management of diabetes and prevention of complications. Learning Outcomes Plan the referral process to specialists when necessary for diabetic complications. Justify the importance of screening, early diagnosis, and treatment of diabetes to prevent end-organ damage and reduce mortality and adverse sequelae. Correlate the potential links between diabetes and other conditions, such as cancer, cardiovascular events, and chronic kidney disease Type 1 and Type 2 Diabetes Diagnosis, classification, management Diabetes Mellitus Derived from the Greek words diabetes = “siphon, to pass through” and mellitus = “sweet” A metabolic disease that involves abnormally elevated blood glucose levels One of the most common chronic diseases and leading causes of disability and mortality (Sapra, 2023, Wang et al., 2021) Reduces lifespan by 5-15 years and the all-cause mortality rate is twice as high as for those without diabetes (Diabetes Canada, 2022) Diabetes Mellitus Globally, 1 in 11 adults between ages 20-79 is diagnosed with diabetes (Sapra, 2023) An estimated 34.2 million (10.5%) in the U.S. have diabetes In Canada, 5.7 million (14%) have diabetes Since 2000, the age-standardized prevalence rate has increased by an average of 3.3% each year The all-cause mortality rate among those with diabetes has decreased – suggesting that patients are living longer with a diabetes diagnosis Diabetes Mellitus Both genetic and environmental factors play a role in the development of diabetes The two main subtypes: Type 1 and Type 2 diabetes Other subtypes include: maturity-onset diabetes of the young, gestational diabetes, secondary causes due to endocrinopathies/steroid use, etc. Type 1 Diabetes Type 1 Diabetes: Epidemiology Due to the destruction of pancreatic islet beta cells – typically secondary to an autoimmune reaction More commonly in children and young adults, with peak incidence at ages 4-6 and 10-14 The global incidence of Type 1 diabetes is increasing: approximately 3% each year One-third of the disease susceptibility is due to genetic factors, with two-thirds attributed to environmental factors Type 1 Diabetes: Epidemiology The genetic factors: The HLA locus (HLA-DR3, -DR4, -DQ) confers about 40% of the genetic risk to developing Type 1 diabetes Most patients will have circulating antibodies to islet cells, glutamic acid decarboxylase 65, insulin, tyrosine phosphatase IA2, and zinc transporter 8 Type 1 Diabetes: Epidemiology The environmental factors: Highest incidence in Scandinavia and northern Europe (e.g., in Finland, the annual incidence is 40 per 100,000 children aged ≤14 years); lowest in China and parts of South America (annual incidence is 9lb Type 2 Diabetes: Epidemiology The genetic factors: Epidemiologic studies looking at monozygotic twins >40 years of age have shown that when Type 2 diabetes develops in one twin, in 70% of cases the second twin will also develop Type 2 diabetes within a year Genome studies have identified 143 risk variants and regulator mechanisms for Type 2 diabetes, including loci that code for proteins involved in beta cell function/development (TCF7L2), insulin secretion (e.g., CDKAL1, SLC30A8), fat mass and obesity risk (FTO, MC4R), and insulin resistance (PPARG) Type 2 Diabetes: Epidemiology The environmental factors: Obesity (in particular, visceral obesity) is the most significant environmental factor causing insulin resistance. Subcutaneous abdominal fat has less correlation with insulin resistance. “Metabolic obesity” = increased visceral fat in patients with Type 2 diabetes without overt obesity Type 2 Diabetes: Epidemiology The environmental factors: Adipocytes secrete abnormal levels of adipokines (e.g., adiponectin and resistin) that can impair insulin signaling The release of TNF-alpha and IL-6 by macrophages and other immune cells activated in adipose tissue can also impair insulin signaling Type 2 Diabetes: Epidemiology Many patients have an insidious onset of hyperglycemia and are initially asymptomatic. Diabetes is recognized only after glycosuria or hyperglycemia is discovered on routine lab testing. At the time of diagnosis, patients may already have some level of neuropathic or cardiovascular complications Type 2 Diabetes: Epidemiology Prevalence of diabetes among adults in the lowest income group is 4.9 times higher than in adults of the highest income group Prevalence of diabetes among adults who have not completed high school is 5.2 times higher than in adults with a university education Prevalence of diabetes among adults who are permanently unable to work is 2.9 times higher than in employed adults Type 2 Diabetes: Epidemiology The majority of patients with diabetes pay >3% of their income (>$1500) per year for prescribed medications, devices, and supplies out-of-pocket Among Canadians with Type 2 diabetes, 33% do not feel comfortable disclosing their disease to others (Diabetes Canada, 2022) Type 2 Diabetes: Signs and Symptoms Chronic skin conditions: Vulvovaginal candidiasis in females Balanoposthitis in males Acanthosis nigricans Eruptive xanthomas Acanthosis nigricans of the nape of the neck, with typical dark and velvety appearance. (Used, with permission, from Umesh Masharani, MB, BS, MRCP [UK].) Citation: 29-01 Diabetes Mellitus, Papadakis MA, McPhee SJ, Rabow MW, McQuaid KR, Gandhi M. Current Medical Diagnosis & Treatment 2024; 2024. Available at: https://accessmedicine.mhmedical.com/content.aspx?bookid=3343&sectionid=280095764 Accessed: September 05, 2024 Copyright © 2024 McGraw-Hill Education. All rights reserved Eruptive xanthoma. (Used, with permission, from Mary Malloy, MD, University of California, San Francisco.) Citation: 29-01 Diabetes Mellitus, Papadakis MA, McPhee SJ, Rabow MW, McQuaid KR, Gandhi M. Current Medical Diagnosis & Treatment 2024; 2024. Available at: https://accessmedicine.mhmedical.com/content.aspx?bookid=3343&sectionid=280095764 Accessed: September 05, 2024 Copyright © 2024 McGraw-Hill Education. All rights reserved Type 2 Diabetes: Signs and Symptoms Weight gain Overweight or obese Centripetal fat distribution Waist circumference >40 inches for men, >35 inches for women Obstetrical complications Consider Type 2 diabetes in women who have delivered babies over 9 lb (4.1 kg) or have had polyhydramnios, preeclampsia, or unexplained fetal losses Type 2 Diabetes: Screening Recommendation Screening IS recommended for Type 2 diabetes (USPSTF) Reliable tests are available, plus lifestyle changes and medications reduce disease progression and adverse sequelae even in patients who are initially asymptomatic (Pippitt et al., 2016) Although screening did not improve mortality at 10-year follow-up, lifestyle and pharmacologic interventions can delay the development of Type 2 diabetes Some studies suggest that screening may confer benefits in mortality at 23- to 30-year follow-up Type 2 Diabetes: Screening Recommendation Screen asymptomatic adults with a body mass index ≥25 kg/m2, and one or more additional risk factors (American Diabetes Association, ADA) from previous lab results: A1c > 5.7% Impaired glucose tolerance Impaired fasting glucose Clinical Features of Diabetes at Diagnosis Type 1 Diabetes Type 2 Diabetes Polyuria and thirst ++ + Weakness or fatigue ++ + Polyphagia with weight loss ++ - Recurrent blurred vision + ++ Vulvovaginitis or pruritis + ++ Peripheral neuropathy + ++ Nocturnal enuresis ++ - Often asymptomatic - ++ “Metabolic Syndrome” Insulin Resistance Syndrome Identifies individuals at higher risk for developing diabetes and cardiovascular disease Usefulness as diagnostic or management tool? No pathophysiologic basis for the syndrome (WHO, 2010) Only modest association between metabolic syndrome and cardiovascular disease Other measures (e.g., Framingham risk score, fasting glucose) are shown to be more useful than the ”metabolic syndrome” label Additional Types of Diabetes Additional Types of Diabetes Gestational diabetes Diabetes in children and adolescents Diabetes in geriatric patients Secondary causes of diabetes Gestational Diabetes Comprised 7.8% of all pregnancies in 2020 (Centers for Disease Control and Prevention, U.S.) – a 13% increase since 2019 and 30% increase since 2016 Prevalence increases with advancing age and a greater pre- pregnancy BMI 2.5% in those aged 40 years Only 2 in 5 women in the U.S. with a live birth in 2020 had a normal BMI prior to pregnancy Gestational Diabetes Screening is typically done between 24-28 weeks’ gestation with a non-fasting 50g glucose challenge test If blood glucose >140 mg/dL (7.8 mmol/L), then perform a 3-hour fasting 100g glucose challenge test to confirm (Diagnostic) Positive if there is at least one abnormal value (≥180, 155, 140 mg/dL for 1-, 2-, and 3-hour fasting glucose levels, respectively) A threshold value of 130 mg/dL (7.2 mmol/L) is more sensitive (99%) but less specific (77%) than a cutoff of 140 mg/dL (85% sensitivity, 86% specificity) Gestational Diabetes One-step testing: a single fasting 75g oral glucose tolerance test Two-step testing: a non-fasting 50g oral glucose tolerance test, followed by a 3-hour fasting 100g glucose tolerance test if the result passed the threshold of 130-140 mg/dL (7.2-7.8 mmol/L) Diagnosis of gestational diabetes is more common in one-step screening (16.5%) than two-step screening (8.5%) – but no statistically significant differences in perinatal or maternal complications Diagnosis of gestational diabetes is associated with increased psychological and emotional burden Gestational Diabetes Conclusion: the two-step testing produces equivalent benefits and fewer harms than the one-step testing approach Gestational Diabetes: Screening Recommendations To reduce maternal and fetal complications. E.g., preeclampsia, caesarean delivery, congenital malformations, macrosomia, childhood or adolescent obesity, nerve palsy, bone fracture, jaundice, and infant death Screen women in their first trimester if risk factors are present, such as obesity, advanced maternal age or >35 years of age, history of gestational diabetes, family history of diabetes, belonging to a high- risk ethnic group (ADA, American College of Obstetricians and Gynecologists, Centers for Disease Control and Prevention) Screen asymptomatic patients at or after 24 weeks’ gestation (American Academy of Family Physicians, USPSTF) Gestational Diabetes: Complications Adverse outcomes include: gestational hypertension (RR=1.6), preeclampsia (RR=1.5), Cesarean delivery (RR=1.3), shoulder dystocia (RR=2.9), macrosomia (RR=1.6), and birth defects (RR=1.2) 7 times greater maternal risk of developing Type 2 diabetes later in life (RR=7.4) and 1.5 times greater risk of the child being overweight in childhood/adolescence (RR=1.5) In high-risk populations (BMI >25 kg/m2 plus physical inactivity, first- degree relative with diabetes, high-risk ethnicity, previous gestational diabetes, or hypertension), diabetes develops in up to 50% of women with gestational diabetes Gestational Diabetes: Management Short- and long-term follow-up is critical Screening at 6-12 weeks postpartum with a fasting glucose measurement or a 75g 2-hour glucose tolerance test. Up to 36% of women with gestational diabetes may have persistently abnormal glucose tolerance. Women with history of gestational diabetes should be screened every 3 years for overt diabetes Diabetes in Children and Adolescents Type 1 diabetes Type 2 diabetes Maturity-onset diabetes of the young (MODY) Diabetes in Children and Adolescents In 2018, an estimated 210,000 children and adolescents in the U.S. (2.5 per 1000) had diabetes Approximately 23,000 had Type 2 diabetes (0.24 per 1000) From 2005-2016, almost 20% of youth 12-18 years of age had prediabetes Most cases occur after age 10, with peak occurrence at mid- puberty Type 2 Diabetes in Children and Adolescents Risk factors include: obesity, excess adipose tissue (especially when centrally distributed), and family history Prevalence is highest in Native American, Black, Latin American, and Atlantic/Pacific Islander youth (U.S.) Socioeconomic position, area of residence, and environmental factors may also play a role (e.g., quality of and access to health care, toxic stress, structural racism) Type 2 Diabetes in Children and Adolescents Major acute complications of Type 2 diabetes in youth are diabetic ketoacidosis (10% at diagnosis) and hyperglycemic hyperosmolar state Long-term morbidity is due to macrovascular (atherosclerosis) and microvascular diseases (retinopathy, nephropathy, neuropathy) May develop complications of renal disease, retinopathy (13.7%), and peripheral neuropathy (17.7%) during teenage and young adulthood years Increased prevalence of associated chronic comorbid conditions: hypertension (11.6-33.8%), dyslipidemia (4.5-10.7%), and nonalcoholic fatty liver disease (22.2%) Type 2 Diabetes in Children and Adolescents: Screening “Evidence is insufficient” to assess the benefits verses harms of screening for Type 2 diabetes in children and adolescents (USPSTF) “Insufficient evidence” to recommend for or against screening for Type 2 diabetes in children and adolescents without symptoms of diabetes or prediabetes (USPSTF) “Inadequate evidence” that screening and early intervention lead to improvements in health outcomes such as prevention of: the progression to Type 2 diabetes, renal impairment, cardiovascular morbidity, mortality, and quality of life (USPSTF) Type 2 Diabetes in Children and Adolescents: Screening Recommendations Screening recommended for age ≤18 who are overweight and have any two of the following risk factors: history of Type 2 diabetes in a first- or second-degree relative, belonging to a high-risk ethnic group, acanthosis nigricans, hypertension, hyperlipidemia, or polycystic ovarian syndrome (ADA) Screening recommended for at-risk patients every 2 years, starting at age 10, or at onset of puberty if under age 10 (American Academy of Pediatrics, ADA) Maturity-Onset Diabetes of the Young (MODY) A non-insulin-dependent form of diabetes, typically diagnosed at ≤25 years of age 1-5% of all patients with diabetes have the MODY type Often misdiagnosed as Type 1 or 2 diabetes Maturity-Onset Diabetes of the Young (MODY) MODY should be suspected in patients who are/have: Non-obese and were diagnosed with diabetes at a young age (144 mg/dL or 8.0 mmol/L, and no laboratory evidence of pancreatic beta cell autoimmunity) Maturity-Onset Diabetes of the Young (MODY) Most often an autosomal dominant disease, with 50% of offspring affected Divided into 14 subtypes (MODY1 to MODY14), with MODY1 to MODY3 accounting for 95% of cases The subtypes are distinguished by their gene mutations: MODY1 (HNF4A): rare MODY2 (GCK): less rare MODY3 (HNF1A): most common, 30-50% of cases Remaining subtypes are very rare Maturity-Onset Diabetes of the Young (MODY) MODY1 and MODY3 have progressive hyperglycemia and vascular complication rates similar to patients with Type 1 and Type 2 diabetes MODY2 has mild stable fasting hyperglycemia with low risk of diabetes-related complications. These patients generally do not require treatment, except in pregnancy. Maturity-Onset Diabetes of the Young (MODY): Screening Recommendations Consider genetic testing and referral to endocrinologist and/or clinical genetics consultant Accurate diagnosis of MODY will determine treatment and management plan However, there is a lack of evidence from randomized trials to show that early diagnosis and appropriate therapy improve patient-oriented outcomes (Kant et al., 2022) Diabetes in Older Adults The definition of “older” differs across studies; generally accepted as >65 years of age From 1997-2010, the U.S. prevalence of diabetes in older adults increased by 62% (Laiteerapong and Huang, 2018) In the U.S., 21.4% of adults aged ≥65 years have a known diagnosis of diabetes; 16% are unaware that they have diabetes (found on glycosylated hemoglobin, fasting plasma glucose, or oral glucose tolerance testing) Diabetes in Older Adults Most commonly affected by Type 2 diabetes The older diabetic population is highly heterogeneous in regards to race/ethnicity, duration of diabetes, comorbidity, and functional status, which complicates the development of standard guidelines of care Diabetes increases the risk of mortality and cardiovascular and microvascular complications, as well as other geriatric conditions (e.g., cognitive impairment, frailty, unintentional weight loss, polypharmacy, and functional impairment) Diabetes in Older Adults: Screening Recommendations No current recommendations for routine screening Screening is dependent on whether treatment would improve overall quality of life or life expectancy Consider screening to prevent complications that may lead to functional impairment (ADA) Decisions regarding treatment should be made based on age, life expectancy, functional status, and the presence of chronic co-morbid diseases Secondary Causes of Diabetes Secondary causes include: exocrine pancreas diseases, endocrinopathies, drug- or chemical-induced insulin resistance, and other genetic diseases Any disorder that damages the pancreas can result in diabetes (e.g., liver cirrhosis, hemochromatosis, hemosiderosis) Secondary Causes of Diabetes Exocrine Pancreas Endocrinopathies Drug- or Chemical- Genetic Syndromes Diseases induced Pancreatitis Somatostatinoma Corticosteroids Down Cystic Fibrosis Pheochromocytoma Sympathomimetics Klinefelter Acromegaly Niacin Turner Cushing syndrome Alpelisib Wolfram syndrome Glucagonomia Sirolimus Type A insulin resistance Pheochromocytoma Thiazide diuretics Leprechaunism Phenytoin Rabson-Mendenhall syndrome Atypical antipsychotics Lipoatrophic diabetes Diagnostic Tests Testing for Diabetes Fasting plasma glucose levels (FPG) Oral glucose tolerance test (OGTT) Glycated hemoglobin (HbA1c) Additional tests (urine, self-monitoring, continuous glucose monitoring, autoantibody, genetic) Fasting Plasma Glucose (FPG) 100-125 mg/dL (5.6-6.9 mmol/L) = impaired fasting glucose tolerance – increased risk of diabetes (“pre-diabetes”) ≥126 mg/dL (7.0 mmol/L) on more than one occasion, after at least 8-hour fasting = Diagnostic Diagnosis may be made with hyperglycemia signs and symptoms, PLUS >200 mg/dL (11.1 mmol/L) – and testing should be repeated to confirm Pros: may identify one-third more undiagnosed cases than A1c Cons: fasting is required Oral Glucose Tolerance Test (OGTT) Perform if FPG is