Carbohydrates: Clinical applications Carbohydrate metabolism disorders include: Hyperglycemia: increased blood glucose Hypoglycemia: decreased blood glucose Inborn errors of metabolism Diagnostic criteria have shifted away from the Oral Glucose Tolerance Test (OGTT) to Fasting Plasma Glucose (FPG) test with a threshold of 126 mg/dL (7 mmol/L)

Carbohydrates: Clinical applications Impaired glucose tolerance (IGT): plasma glucose levels ‘borderline’ abnormal following OGTT, but not high enough for the patient to be considered diabetic Impaired fasting glucose (IFG): plasma glucose levels above normal following FPG, but not significantly high for the patient to be considered diabetic Patients with IGT and IFG have a bigger risk of developing diabetes mellitus; they may also revert back to normal, or may remain borderline.

Carbohydrates: Clinical applications Hyperglycemia Grouped into four main categories: 1. Type 1 diabetes mellitus: insulin- dependent diabetes mellitus (IDDM) 2. Type 2 diabetes mellitus: non-insulin-dependent diabetes mellitus (NIDDM) 3. Gestational diabetes mellitus (GDM) 4. Others (genetic defects, infections, endocrinopathies etc.)

Hyperglycemia Diabetes mellitus: heterogeneous group of disorders characterized by a deficiency in insulin production, Secretion, or action, resulting in hyperglycemia 1. Type 1 diabetes mellitus (IDDM) - complete deficiency of insulin usually due to auto- immune destruction or degeneration of pancreatic islet cells - combination of genetic determinants and environmental factors (viruses, chemicals) Carbohydrates: Clinical applications

1. Type 1 diabetes mellitus (cont’d) - type 1 diabetic patients usually present with increased levels of several auto-antibodies, including islet cell auto-antibodies and insulin auto-antibodies Symptoms of diabetes type 1 - rapid weight loss - ketonemia - excessive drinking - ketonuria - polyuria - acidosis - electrolyte imbalance; increased serum osmolality and specific gravity Carbohydrates: Clinical applications

1. Type 1 diabetes mellitus (cont’d ) Complications of diabetes type 1 - renal - cardiac - neurovascular - onset of type 1 diabetes: at any age- most common in juveniles (known as juvenile diabetes, accounts for 10% of all cases of diabetes mellitus) Carbohydrates: Clinical applications

2. Type 2 diabetes mellitus (NIDDM) - most common form of diabetes (80%-90%) - relative deficiency in insulin activity due to insulin resistance or secretion disorders - type 2 diabetic patients present with increased amyloid deposition (amyloidosis) in pancreatic islet cells, which leads to a proportional increase in glucose intolerance - genetic predisposition Carbohydrates: Clinical applications (

2. Type 2 diabetes mellitus (cont’d) - environmental factors such as obesity and lack of physical exercise are important factors in the predisposition to type 2 diabetes - no association with autoimmune antibodies or infections - onset: over age of 40 Clinical symptoms - vascular - obesity - insulin treatment is not absolutely necessary Carbohydrates: Clinical applications

3. Other specific types of diabetes onset of hyperglycemic symptoms secondary to: - genetic defects of cell function or insulin action - pancreatic exocrine disorders - endocrine diseases - drug or chemically-induced conditions - infections - auto-antibodies against insulin receptors Carbohydrates: Clinical applications

3. Other specific types of diabetes a. genetic defects of cell function or insulin action - Maturity onset diabetes for youth (MODY): impaired insulin secretion - Mitochondrial diabetes mellitus (MtDM): maternal co- transmission of diabetes and deafness - genetic defects preventing conversion of pro-insulin to insulin - mutated insulin peptide resulting in decreased binding to insulin receptors Carbohydrates: Clinical applications

3. Other specific types of diabetes a. genetic defects of cell function or insulin action (cont’d) - mutations in insulin receptor (type A insulin resistance) or enzymes/molecules in the insulin signaling pathway b. Exocrine pancreatic disorders - pancreatitis - pancreatic carcinoma Carbohydrates: Clinical applications

3. Other specific types of diabetes (cont’d) c. Endocrinopathies - Cushing’s disease (increased cortisol) - Glucagonoma (increased glucagon ) - Acromegaly (increased GH) - Pheochromocytoma (increased epinephrine) d. Drug- or chemically induced hyperglycemia - hormones or drugs which are insulin antagonists that can impair pancreatic cell function may eventually lead to hyperglycemia Carbohydrates: Clinical applications

3. Other specific types of diabetes (cont’d) e. Infections - cytomegalovirus - congenital rubella f. Auto-antibodies against insulin receptors - type B insulin resistance ** however, some auto-antibodies mimic insulin action and may result in hypoglycemia ** Carbohydrates: Clinical applications

4. Gestational diabetes mellitus (GDM) - onset of impaired glucose tolerance (IGT) during pregnancy due to hormonal or metabolic changes - usually accompanied with a family history of diabetes mellitus - most significant consequences of hyperglycemia are related to the fetus: congenital malformations and perinatal mortality - mother needs to be monitored and tested for FPG levels six weeks post-partum Carbohydrates: Clinical applications