Endocrine System Diseases

• Diseases of the Endocrine System are the topic of these notes.

Introduction

• The endocrine system is a complex functional system, not just an anatomical one.
• Endocrine glands are scattered throughout the body.
• These glands secrete hormones, which are chemical messengers.
• A single gland can secrete multiple hormones.
• A single hormone can be secreted by multiple glands.

Normal Anatomy and Physiology

• Hormones are released when their actions are needed and inhibited when the desired effects are achieved.
• Endocrine diseases show effects through hyperfunction, hypofunction, or abnormal target cell responsiveness.
• Hyperfunction refers to exceptionally high blood concentrations of a hormone.
• Hypofunction refers to depressed levels of hormones in the blood.
• Abnormal target cell responsiveness results in hypofunction.
• Most cases of hypo-responsiveness stem from a lack or deficiency of hormone receptors on target cells.
• Major hormone functions include reproduction, sexual differentiation, growth, development, homeostasis, and regulation of metabolism and nutrient supply.

Endocrine Function of the Pancreas

• The pancreas secretes hormones regulating energy metabolism and fuel homeostasis.
• The exocrine pancreas is responsible for secreting fluid and digestive enzymes.
• The endocrine pancreas is made up of islets of Langerhans.
• Alpha cells in the islets of Langerhans secrete glucagon.
• Beta cells within the islets secrete insulin.

Endocrine Control of Energy Metabolism

• Energy use in the body is constant, while nutrient ingestion is sporadic.
• Carbohydrates, fats, and proteins are stored as energy.
• In the fed state, nutrients are absorbed into the bloodstream after ingestion.
• Glucose functions as the main energy source during the fed state.
• Unused glucose or fat is stored as glycogen and/or triglycerides.
• Proteins are used to build and repair tissue in the fed state with any remaining protein considered a "last resort" energy source.
• During the fasting state, endogenous energy stores are mobilized.
• Pancreatic hormones manage and control homeostasis.

Insulin

• Insulin is anabolic
• Insulin controls the metabolic fates of carbohydrate, protein and lipid
• Insulin facilitates carbohydrate metabolism by transporting blood glucose into cells when blood levels are high.
• Insulin stimulates glycogen synthesis, promotes glucose oxidation, and stimulates glucose storage.
• Most tissues depend on insulin for glucose transportation from the bloodstream into cells for energy.
• The brain and liver are not insulin dependent.

Glucose Transporters

• GLUT-1 transports glucose in most cells, including across the blood-brain barrier.
• GLUT-2 transports glucose in the liver, pancreatic beta cells, hypothalamus, basolateral membrane of the small intestine, and kidney tubules, moving it into adjacent bloodstream via co-transport.
• GLUT-3 transports glucose into neurons within the brain, kidney, placenta, and testes.
• GLUT-4 transports the majority of glucose used by most cells of the body via the influence of insulin.
• GLUT-5 transports fructose and is located in the intestinal mucosa, adipose tissue, skeletal muscle, and sperm.

Insulin - Protein Metabolism

• Insulin promotes active transport of amino acids into muscle and other tissues, facilitating protein synthesis.
• Insulin produces a positive nitrogen balance.
• When insulin is deficient, there is a net loss of protein, resulting in a negative nitrogen balance.

Glucagon

• Glucagon is released from alpha cells when glucose levels fall.
• Glucagon stimulates the breakdown of glycogen (glycogenolysis).
• Glucagon stimulates the production of new glucose from amino acids (gluconeogenesis).
• Glucagon stimulates lipolysis, which provides additional substrate to meet energy requirements.

Diabetes Mellitus

• Diabetes Mellitus is the most common of all endocrine disorders.
• Approximately 15% of American adults have diabetes.
• About 30% of diabetes cases are undiagnosed.
• Diabetes is a group of disorders characterized by hyperglycemia.
• Diabetes results from defects in insulin production, action, or both.
• Chronic hyperglycemia correlates with damage to and/or failure of the eyes, kidneys, nerves, heart, and blood vessels.

Classifications of Diabetes

• Type 1 diabetes involves the autoimmune destruction of beta cells. This results in absolute insulin deficiency.
• Type 2 diabetes involves progressive defective insulin secretion coupled with insulin resistance.
• Gestational diabetes (GDM) is diagnosed in the second or third trimester of pregnancy.
• Diabetes can also develop due to other causes such as drug or chemical induction (e.g., after organ transplants), genetic defects, or due to cystic fibrosis or other diseases of the pancreas.
• Prediabetes is a category with increased risk for diabetes.

Type 1 Diabetes Mellitus

• Accounts for 5-10% of diagnosed diabetes cases.
• This form that typically develops in children and adolescents, is increasingly being diagnosed later in life, even in older adults.
• T1DM is an immune-mediated disease from a cell-mediated autoimmune response.
• This response gradually declines beta cell mass within genetically susceptible individuals.
• Individuals with relatives who have T1DM are at higher risk.
• Environmental factors and gene interactions appear to be significant in T1DM.
• Proposed environmental triggers for the autoimmune response include viral infections, casein, gluten, vitamin D levels, infant feeding practices, and breastfeeding duration.

Type 1 Diabetes Mellitus: Pathophysiology

• T1DM presents a deficiency in insulin because of pancreatic beta cell destruction.
• The destruction of pancreatic beta cells results in the inability of cells to use glucose for energy.
• Signs and symptoms of T1DM emerge around the time that 60%-80% of beta cells have been destroyed.
• The cell starvation causes hyperglycemia.
• Clinical symptoms include glycosuria, polyuria, polydipsia, polyphagia, weight loss, and ketoacidosis.

Type 2 Diabetes: Epidemiology

• Accounts for 90-95% of diagnosed diabetes cases worldwide.
• Risk factors include obesity, family history, history of gestational DM, race, ethnicity, advancing age, physical inactivity, and poor diet.
• Race and ethnicity risk factors include African Americans, Hispanic Americans, certain Asian Americans, Native Americans, and Pacific Islanders who are at increased risk.

Type 2 Diabetes: Etiology

• Evolves from a combination of abnormal insulin secretion and insulin resistance.
• It's considered polygenic (multiple genes involved).
• Primary environmental factors include obesity (especially central body adiposity) and poor diet.
• Physical inactivity increases risk.
• Exercise reduces T2DM risk by enhancing whole-body insulin sensitivity.
• High birth weight is a risk factor.
• Identifiable gene defects have been found in most families with this pattern of diabetes.

Type 2 Diabetes Mellitus: Pathophysiology

• Individual's body produces insulin, but tissues are insulin resistant.
• Insulin resistance is caused by a cell receptor defect.
• The pancreas increases insulin production but cannot maintain high levels for long.
• Results in the development of a relative insulin deficiency.
• Postprandial (after-meal) glucose levels initially rise due to the inability of the cells to utilize glucose.
• Hepatic gluconeogenesis steps up to compensate for the lack of glucose within cells, which results in fasting hyperglycemia.

Type 2 Diabetes Mellitus: Clinical Manifestations

• Insidious onset.
• Often asymptomatic but presents with complications associated with diabetes.
• Clinical symptoms include glycosuria, polyuria, polydipsia, polyphagia, weight loss, fatigue, recurrent infections, slow healing wounds.

Pre-Diabetes

• Prediabetes is a high-risk factor for development of diabetes.
• Diagnosis is made for individuals with impaired fasting glucose or impaired glucose tolerance.
• Early intervention and lifestyle changes are important.

Pre-Diabetes Diagnosis

• A1C of 5.7-6.4% (39-47 mmol/mol).
• FPG of 100 mg/dL (5.6 mmol/L) to 125 mg/dL (6.9 mmol/L).
• 2-h PG during 75-g OGTT of 140 mg/dL (7.8 mmol/L) to 199 mg/dL (11.0 mmol/L).

Nutrition Therapy for Pre-DM

• Intensive lifestyle management includes a 7% loss in body weight.
• ≥150 min/week of moderate intensity physical activity (such as brisk walking).
• A variety of eating patterns can be considered (Mediterranean, DASH, Vegetarian).

Diabetes Mellitus: Acute Complications

• Hypoglycemia is a side effect and complication of insulin therapy.
• Dawn phenomenon is when hyperglycemia occurs between 5 a.m. and 9 a.m due to hormones controlling circadian rhythms
• Diabetic ketoacidosis is a life-threatening form of severe hyperglycemia.

Diabetes Mellitus: Long-term Complications

• Long-term complications of hyperglycemia include cardiovascular disease and nephropathy.
• Retinopathy is a potential complication from long-term hyperglycemia.
• Neuropathy includes peripheral neuropathy, gastroparesis, sexual dysfunction, and bladder emptying problems.

Diabetes Mellitus Diagnosis

• Diagnosed with A1C ≥6.5% (≥48 mmol/mol).
• Diagnosed with FPG ≥126 mg/dL (≥7.0 mmol/L).
• Diagnosed with 2-h PG ≥200 mg/dL (≥11.1 mmol/L) during OGTT.
• Diagnosed with random plasma glucose ≥200 mg/dL (≥11.1 mmol/L).

Diagnosis of Diabetes Mellitus

• Glycated hemoglobin assays measure the amount of glucose bound to hemoglobin protein.
• A1C can measure the average glucose concentration for the previous 3 months due to the 120 day lifespan of red blood cells.
• Oral glucose tolerance test (OGTT) is a standard screening for gestational diabetes.
• Islet cell autoantibodies are used to differentiate between autoimmune T1DM and T2DM.

Diagnosis of Diabetes Mellitus - Staging

• Presence of 2 or more autoantibodies; Euglycemia (normal FPG and PPG), pre-symptomatic signifies Stage 1 diabetes.
• Presence of multiple autoantibodies; Dysglycemia (increased fasting plasma glucose and/or impaired glucose tolerance); FPG of 100-125 mg/dL; PPG of 140-199 mg/dL signifies Stage 2 diabetes.
• Stage 3 diabetes is Symptomatic form where diabetes can be diagnosed by standard criteria.

Medical Treatment of Diabetes Mellitus

• Patient-centered goals include avoiding hyperglycemia, retarding the development of complications, and attention to cardiovascular risk.
• Pharmacotherapy should be considered in order to manage weight, minimize the progression of hyperglycemia, and support cardiovascular risk reduction goals.

Medical Treatment of Diabetes Mellitus

• T1DM is treated with exogenous insulin, nutrition therapy, and physical activity.
• Insulin is classified based on its expected onset, peak time, and duration of action.
• Rapid or short-acting insulin is used as a bolus before meals.
• Long or ultra long-acting insulin is used for basal coverage.
• Total dose of insulin/d: Divide an individual's weight in pounds by the number 4 or multiply the weight in kg by 0.55.
• 50% of the total insulin dose is given as basal insulin and 50% for meals.
• 1 insulin unit for every 10-15g CHO.
• Variety of glucose lowering medications including GLP-1s, nutrition therapy, and lifestyle changes are used to treat T2DM.

Nutrition Therapy for Diabetes Mellitus

• Nutrition Intervention goals are individualized glycemic, blood pressure, and lipid goals.
• Nutrition Intervention plans should promote healthful eating patterns and seek to achieve and maintain body weight goals.
• Nutrition Intervention plans should delay or prevent complications of diabetes and address individual nutrition needs.
• A Nutrition Intervention will maintain the pleasure of eating and provide the individual with practical tools for day-to-day meal planning.

Nutrition Therapy for Diabetes Mellitus: Nutrition Intervention goals

• For overweight/obese patients, the primary goal is weight loss + glycemic management.
• Diagnose with BMI +/- measurements of body fat distribution (Waist circumference, waist-hip ratio).
• Weight loss goal: 3%-7% of baseline weight.
• Sustained loss of >10% of body weight usually confers greater benefits.
• Follow up every 3 months, but monitor at least annually.

Nutrition Therapy for Diabetes Mellitus: Nutrition Prescription

• Nutrition, physical activity, and behavioral therapy are recommended to achieve weight loss goals.
• Interventions include a high frequency of counseling (>=16 sessions in 6 months).
• Nutrition recommendations should be individualized to the person's preferences and nutritional needs.
• Aim for a 500-750 kcal/day energy deficit when able.
• Use nutritional plans that create an energy deficit, regardless of macronutrient composition, to achieve weight loss.
• For those who achieve weight loss goals, it is important to continue to monitor progress and providing ongoing support.
• Effective long-term (>=1 year) weight maintenance programs provide monthly contact and support.
• These programs include frequent self-monitoring of body weight (weekly or more frequently) and other self-monitoring strategies (e.g., food diaries or wearables).
• Regular physical activity (200–300 min/week) is also a part of theses programs.
• Macronutrient distribution should be based on individual assessment of current eating patterns, preferences and metabolic goals.
• Focus on nonstarchy vegetables, whole fruits, legumes, whole grains, nuts, seeds, and low-fat dairy products and minimizing consumption of red meat, sugar-sweetened beverages, sweets, refined grains, and processed and ultra-processed foods.
• A variety of eating patterns are acceptable for the management of diabetes (Mediterranean, low carbohydrate, vegetarian, plant-based, DASH).
• Monitoring carbohydrate intake is a key strategy in reaching glucose goals in people with type 1 and type 2 diabetes.

Nutrition Therapy for Diabetes Mellitus: Macronutrient Specific Nutrition Prescription

• Emphasize minimally processed, nutrient-dense, high-fiber sources of carbohydrate.
• Advise people with diabetes and those at risk to replace sugar-sweetened beverages with water or low-calorie or no-calorie beverages as much as possible.
• Regardless of diabetes classification, individuals treated with sodium-glucose cotransporter 2 inhibitors should avoid a ketogenic eating pattern.
• Provide education on the glycemic impact of carbohydrate, fat, and protein tailored to an individual's needs, insulin plan, and preferences to optimize mealtime insulin dosing.
• When using fixed insulin doses, individuals should be provided with education about consistent patterns of carbohydrate intake with respect to time and amount.
• Incorporate more plant-based protein sources.
• Consider an eating plan emphasizing elements of a Mediterranean eating pattern.
• Limit intake of foods high in saturated fat.

American Diabetes Association Diabetes Care Manual 2025: Nutrition recommendations for DM

• An individualized medical nutrition therapy program, as needed to achieve treatment goals and provided by a registered dietitian nutritionist, is recommended for all people with diabetes or prediabetes as it can result in both cost savings and improved cardiometabolic outcomes.
• Weight management treatment should be based on nutrition, physical activity, and behavioral therapy for all people with overweight or obesity who are trying to lose weight (>3-7%)
• Encourage meal plans that keep nutrient quality, total calories, and metabolic goals in mind while minimizing emphasis on macronutrient pattern.
• Diet plans should emphasize key nutrition principles, including the addition of nonstarchy vegetables, whole fruits, legumes, lean proteins, whole grains, nuts and seeds and low-fat dairy alternatives, and the elimination of red meat, sweets, refined and processed foods.
• Consider Carbohydrate intake reduction as part of any diabetes diet plan.
• Supplementation with micronutrients or herbs or spices is not recommended.
• Counsel against B-carotene supplementation.
• Adults with diabetes should follow all limits regarding alcohol consumptions and should also be educated about the signs, symptoms, and self-management of delayed hypoglycemia after drinking alcohol.
• Recommend people limit their sodium intake consumptions to 2,300 mg/day, and recommend that people people drink water over other beverages, as water can make you feel full to help diet.
• Avoid nutritive sweeteners with nonnutritive sweeteners as short term alternative.

Nutrition Strategies for Individuals with Diabetes

• Emphasize nonstarchy vegetables, dried beans, peas, and lentils.
• Focus on fresh, frozen, or canned fruits without added sugars, when possible
• 100% whole-wheat breads or pastas, and brown rice is preferred for those who require grain.
• Water is the best beverage that should be the primary choice.
• Plant-based proteins, fresh, frozen, or canned meats are good for diets.
• Heart-healthy wild-caught fatty fish and herbs are important additions.
• Minimize sodium and salt preparations in meals, while incorporating onions, garlic, celery, carrots and other vegetables.
• Prepare food in fats high in saturated fat (e.g., butter, shortening, lard, and coconut oil).

Physical Activity

• A wide range of benifits are avaliable: Improved glycemic control, lipids, and blood pressure with positive impact on metabolic abnormalities, reduce risk of cardiovascular disease.
• Reduce stress and improved physical fitness and functional capacity with enhanced quality of life.
• Side effects may involve Hypoglycemia and hyperglycemia which are acute risks of exercise.

ADA diabetes care manual, 2025- Most people with diabetes should engage in 150 min or more of moderate- or rigorous-intensity aerobic activity, while engaging in activity 3 days each week with 2 consecutive days without activity.

• Adults with diabetes should engage in 2-3 sessions/week of resistance exercise on nonconsecutive days, always ensuring the safety aspects of this exercise.
• All people with diabetes should interupt sittin every 30 min regardless of current fitness.

Diabetes Mellitus: Monitoring and Evaluation

• Glycemic control is fundamental.
• Strategies involve Glycated hemoglobin assays (A1C) with continuous blood glucose monitoring.
• Testing for ketones is important, as well as keeping tabs on lipid and blood pressure.
• Adults require monitoring for blood pressure, as well as continuous blood and glucose monitoring.

Summary of Glycemic Goals for Adults:

- A1C < 7.0% (<53 mmol/mol)
- Preprandial capillary plasma glucose 80-130 mg/dL (4.4-7.2 mmol/L)
- Peak postprandial capillary plasma glucose - Peak postprandial capillary plasma glucose and peak plasma glucagon