Carbohydrate Metabolism Disorders & Diabetes

Carbohydrate Metabolism Disorders & Diabetes

• Diabetes is a chronic, metabolic disorder characterized by elevated blood glucose levels.
• Type 2 diabetes is the most common type, typically occurring in adults. It arises when the body becomes resistant to insulin or doesn't produce enough insulin.
• Type 1 diabetes, formerly known as juvenile diabetes, is a chronic condition where the pancreas produces little or no insulin.
• Access to affordable treatment, particularly insulin, is crucial for people with diabetes.
• Globally, an estimated 422 million people have diabetes, with the majority residing in low- and middle-income countries.
• Around 1.5 million deaths annually are directly attributed to diabetes.
• Rates of type 2 diabetes have increased significantly over the past few decades.
• Almost 80% of diabetes cases are in low- and middle-income countries, although high rates are also present in lower-income groups of many middle- and high-income countries.

Health Implications of Diabetes

• Diabetes entails direct effects and long-term complications, such as heart disease and stroke.
• People with diabetes have a twofold higher risk of myocardial infarction compared to non-diabetics of the same age and sex.

Metabolic Syndrome

• Insulin resistance or glucose intolerance is a cluster of metabolic factors associated with cardiovascular disease, diabetes, and stroke.
• This cluster often includes obesity (especially abdominal weight gain), atherogenic dyslipidemia, hypertension, thromboembolic states (elevated fibrinogen levels), and inflammatory states (indicated by raised CRP levels).

Common Symptoms of Diabetes Mellitus (DM)

• DM symptoms involve high blood and urine glucose levels (hyperglycemia and glucosuria).
• Other symptoms include frequent urination (polyuria), excessive thirst (polydipsia), constant hunger (polyphagia), sudden weight loss, and excess ketones (ketonemia and ketonuria) during acute episodes.

Glucose Metabolism Regulation

• Hormone regulation of glucose metabolism involves storing glucose as glycogen and mobilizing stored glucose to maintain blood glucose levels.
• These processes are essential for the brain and other tissues, as glucose is their chief energy source.
• Insulin is the primary hypoglycemic (lowering blood glucose) agent in the body.
• Glucagon, epinephrine, cortisol, and thyroxine are important hyperglycemic (raising blood glucose) agents.

Insulin Signaling Pathways

• Insulin signaling begins with insulin binding to its cell surface receptor, initiating a cascade of phosphorylation/dephosphorylation events, the generation of second messengers, and protein-protein interactions.
• These processes result in various metabolic effects across virtually all tissues.
• Genetic variations and functional changes in insulin signaling pathway proteins cause insulin resistance.

Insulin Signaling Defects

• Mutations in the INSR gene, causing Rabson-Mendenhall syndrome, reduce the number of insulin receptors or impair their function.
• This leads to severe insulin resistance, impacting blood sugar regulation and impacting development.

Classification of Diabetes

• Type 1 diabetes (approx. 5-10%): characterized by insufficient insulin secretion, requiring insulin injections. Individuals are prone to ketoacidosis.
• Type 2 diabetes (most common): typically occurs in older individuals, yet increasing in younger populations, not directly correlated with blood insulin levels. Not reliant on insulin injections. Generally not prone to ketoacidosis.
• Secondary diabetes: develops due to other conditions like pancreatic disease, acromegaly, Cushing's syndrome, glucagonoma, somatostatinoma, severe liver disease, or drug use (e.g., theophylline, oral contraceptives with high estrogen doses).

Impaired Glucose Tolerance (IGT)

• Impaired glucose tolerance (IGT) is a condition where an individual has an abnormal glucose tolerance but no frank fasting hyperglycemia.
• IGT is considered a precursor to type 2 diabetes and is sometimes referred to as pre-diabetes.

Gestational Diabetes (GD)

• GD is a form of diabetes that arises during pregnancy and may later transition into type 2 diabetes.
• Pregnancy-related hormonal changes, including elevated human placental lactogen, cortisol, prolactin, and progesterone, contribute to higher insulin needs during pregnancy.

Complications of Diabetes

• Diabetes can cause complications like retinopathy, neuropathy, angiopathy, nephropathy, susceptibility to infections, hyperlipidemia, ketoacidosis, and hyperglycemic hyperosmolar nonketotic coma (HHNC).
• Type 1 diabetes typically exhibits a greater frequency of these complications.

Hyperlipidemia and Atherosclerosis

• Abnormal triglyceride, cholesterol, and very-low-density lipoprotein (VLDL) levels frequently occur with type 2 diabetes.
• High-density lipoprotein (HDL) levels often are lower in diabetics than in non-diabetic individuals.

Diabetic Ketoacidosis

• In individuals without diabetes, ketoacid production is a minor process.
• In those with diabetes, insulin deficiency results in triglyceride mobilization from adipose tissue, causing an increased rate of fatty acid oxidation. This, in turn, leads to raised ketoacid production and reduced blood pH (acidosis).
• Mortality rates can be high for patients experiencing this.

Hyperglycemic Hyperosmolar Nonketotic Coma (HHNC)

• HHNC is a severe medical emergency characterized by extremely high blood glucose levels, above 600 mg/dL, serum osmolality above 350 mOsm/kg, extreme thirst, frequent urination, and normal or slightly low blood pH with, typically, no ketoacid buildup.
• HHNC requires immediate medical attention and has a relatively high mortality rate.

Hypoglycemia

• Hypoglycemia (low blood glucose) can lead to various neurological complications, ranging from mild problems to severe coma and even death. Symptoms begin at around 50 mg/dL.
• An aggressive use of insulin to maintain normoglycemia is a frequent cause of hypoglycemia.

Function Tests

• Postprandial Plasma Glucose (PPG): This test evaluates glucose clearance from the blood after a carbohydrate load (often 75 g of glucose is preferred over a meal). Two consecutive tests are usually done for diagnosis. Glucose levels of 200 mg/dL or higher at two hours post-ingestion are suggestive of diabetes.
• Oral Glucose Tolerance Test (OGTT): This tests glucose clearance under controlled conditions after glucose ingestion. The ADA provides standardization for this test. Test requires a minimum carbohydrate intake, 8-hour fasting prior to the test, and avoidance of exercise and stress. The WHO recommends blood glucose measurement two hours post-glucose ingestion, greater than 200 mg/dL is suggestive of diabetes. The shape of the glucose tolerance curve can help assess different patient states (e.g. healthy subjects' peak at approximately 1 hour and return to baseline at 2 hours; those with diabetes have a delayed peak or a plateau at 2-3 hours and may not return to baseline).
• Fasting Plasma Glucose (FPG): ADA recommends fasting plasma glucose testing over OGTT to test for diabetes diagnosis.
• Random Plasma Glucose Test: This test be done anytime of day on patient with severe diabetes symptoms. Diabetes is diagnosed at a blood glucose of 200 mg/dL or more.
• Glycated Hemoglobin (HbA1c): This measurement reflects the amount of glucose bound to hemoglobin within red blood cells, providing a measure of average blood glucose levels over a period (typically 2-3 months). This test is reliable and often used to monitor diabetes. Diabetes is diagnosed at increased levels above 6.5%.

Other Test

• Urinary Glucose: Not a great measure of diabetes.
• Urinary Protein: Testing for microalbuminuria (small amounts of albumin in the urine) can indicate early signs of diabetic kidney disease.
• HOMA-IR (Homeostasis Model Assessment for Insulin Resistance) : A calculation involving fasting insulin (FPI) and fasting plasma glucose (FPG). A higher score indicated more insulin resistance. A less than 1 is optimal, 1.9 - less than above signal early resistance, greater than 2.9 signal significant resistance.

Explore the complexities of carbohydrate metabolism disorders, focusing on diabetes types and their global impact. Understand the crucial role of insulin and the significance of accessible treatment for millions affected worldwide. This quiz covers the essential facts about diabetes and its health implications.