Medical Concepts

SITUATIONS REQUIRING HOSPITALIZED CARE The NICE-SUGAR (Intensive versus conventional glucose in critically ill patients) trial compared intensive (81-108 mg/dL) with conventional glucose control using IV Insulin in 6104 intensive care unit patients. At 90 days, intensively controlled patients had an increased absolute risk of death of 2.6%. Significantly, more hypoglycemia was observed in intensively controlled group. Recommendations: Current recommendations call for critically ill patients to be started on IV Insulin therapy at a threshold of 180mg/dL. A goal range of 140-180mg/dL is recommended for majority of patients. More stringent goals may be considered for selected critically ill patients, but only if hypoglycemia can be avoided. Scheduled SC insulin regimens with basal, nutritional and correction components are recommended for patients who are not critically ill. Goals of less than 140mg/dL for fasting glucose and less than 180mg/dL for random glucose are recommended for non-

  TREATMENT OF CONCOMINANT CONDITIONS RELATED TO DIABETES MELLITUS Coronary Heart Disease Dyslipidemia Hypertension HIV and AIDS Antipsychotic Therapy Hypoglycemia Diabetic Ketoacidosis (DKA) Hyperosmolar Hyperglycemic state Retinopathy Neuropathy Foot Ulcers  TREATMENT OF LONG-TERM COMPLICATIONS 1. Retinopathy 2. Neuropathy 3.Microablumiuria 4. Foot Ulcers 9.RETINOPATHY Diabetic retinopathy is the leading cause of blindness in adults 20-74 years of age in the United States. Pathophysiology: Diabetic retinopathy occurs when the microvasculature that supplies blood to the retina becomes damaged. This damage permits leakage of blood components through the vessel walls. Etiology: The risk of retinopathy is increased in patients with longstanding DM, chronic hyperglycemia, hypertension and nephropathy. Glaucoma, cataracts and eye disorders are more frequent in pt. with DM. Treatment: The AD recommends that patients with DM receive a dilated eye examination annually by an ophthalmologist or

  TREATMENT OF CONCOMINANT CONDITIONS RELATED TO DIABETES MELLITUS Coronary Heart Disease Dyslipidemia Hypertension HIV and AIDS Antipsychotic Therapy Hypoglycemia Diabetic Ketoacidosis (DKA) Hyperosmolar Hyperglycemic state Retinopathy Neuropathy Foot Ulcers  The Acute Complications Include: Hypoglycemia DKA Hyperosmolar Hyperglycemic state 6. HYPOGLYCEMIA  "Hypoglycemia or low blood sugar can be defined clinically as a blood glucose level of less than 50mg/dL". Signs: Individuals with DM can experience symptoms of hypoglycemia at varying blood glucose levels. Patients who have regular blood glucose levels as high as 300-400mg/dL may experience symptoms of hypoglycemia when blood glucose levels are lowered to the middle to upper mg/dL range. Most people whose blood glucose levels are controlled adequately may experience symptoms when levels fall below 70mg/dL. Symptoms: Shakiness Sweating Fatigue Hunger Headaches Confusion *Patients experiencing symptoms of hypoglycemia shou

  TREATMENT OF CONCOMINANT CONDITIONS RELATED TO DIABETES MELLITUS Coronary Heart Disease Dyslipidemia Hypertension HIV and AIDS Antipsychotic Therapy Hypoglycemia Diabetic Ketoacidosis (DKA) Hyperosmolar Hyperglycemic state Retinopathy Neuropathy Foot Ulcers  3.HYPERTENSION Uncontrolled blood pressure plays a major role in the development of macrovascular events as well as microvascular complications, including retinopathy and nephropathy in patients with Diabetes Mellitus. Medications: There are several other principles regarding the treatment of hypertension in Diabetes patients. Angiotensin-converting enzyme (ACE) inhibitors or Angiotensin II receptor Blockers are recommended as initial therapy because of their beneficial effects on renal function. Combination therapy with ACE Inhibitor and Dihydropyridine calcium channel blockers has shown to reduce cardiovascular morbidity and mortality versus those receiving ACE Inhibitor therapy combined with Thiazide Diuretic. However, th

  TREATMENT OF CONCOMINANT CONDITIONS RELATED TO DIABETES MELLITUS Coronary Heart Disease Dyslipidemia Hypertension HIV and AIDS Antipsychotic Therapy Hypoglycemia Diabetic Ketoacidosis (DKA) Hyperosmolar Hyperglycemic state Retinopathy Neuropathy Foot Ulcers  1.CORONARY HEART DISEASE "Cardiovascular disease is the major cause of morbidity and mortality for patients with DM". Interventions: The interventions to manage CVS disease: Smoking cessation BP Control Lipid management Antiplatelet therapy Lifestyle modification Medications: All DM patients with a history of cardiovascular disease should be prescribed; Aspirin 75-125mg/day as a secondary prevention strategy or Clopidogrel 75mg/day. The ADA recommends that antiplatelet therapy should be considered for any patient with DM as a primary prevention strategy, if that patient is at risk of cardiovascular disease greater than 10% for over 10 years. This includes most men older than 50 years of age and most women older than 60

PHARMACOTHERAPY  NON-INSULIN INJECTABLE AGENTS 1.GLUCAGON-LIKE PEPTIDE 1 AGONSIT: GLP-1 Agonists enhance glucose dependent insulin secretion while suppressing inappropriately high glucagon secretion in the presence of elevated glucose, which results in reduced hepatic glucose production. Exenatide and Liraglutide are both indicated for the treatment of T2 DM to improve glycemic control. Pharmacokinetics: Plasma concentrations are detected up to 10hrs after injection, although pharmacodynamics action lasts for approximately 6hrs. Mechanism of Action: GLP-1 agonists lower blood glucose levels by producing glucose dependent insulin secretion, reducing post meal glucose secretion, which decreases post meal glucose output, increasing satiety which decreases food intake and regulating gastric emptying which allows nutrients to be absorbed into the circulation more smoothly. Clinical uses: In a 26 weeks head-to-tail trial in patients with T2DM with a baseline A1c between 7%-11% who were tak

 INSULIN ADMINISTRATION DEVICES INSULIN PUMP THERAPY: "Insulin pump therapy consists of a programmable infusion device that allows for basal infusion 24hrs daily as well as bolus administration before meals and snacks". Regular or rapid acting insulin is delivered from a reservoir either by infusion set tubing or through a small canula. Most infusion pumps are set in the abdomen, arm or other infusion sites by a small needle.  Most patients prefer insertion in the abdominal tissue because this site provides optimal insulin absorption.  Infusion sets should be changed every 2-3 days to reduce the possibility of infection. Determination of Insulin Units: Patients use carbohydrate-to-insulin ratio to determine how many units of insulin are required.  More specifically, an individual's ratio is calculated to determine how many units of the specific insulin being used in the pump "covers" for a certain amount of carbohydrates to be ingested at a particular level.

PHARMACOTHERAPY Medications classifications include:  Sulfonyl Urea's Nonsylfonylurea Secretagogues (a-Glinides) Biguanides Thiazolidinediones a-Glucosidase Inhibitors Dipeptidyl Peptidase-4 Inhibitors (Gliptins) Sodium-glucose co-transporter (SGLT) Inhibitors  Central-Acting Dopamine Agonists Bile Acid Sequestrants Insulin therapy 10.  INSULIN THERAPY Insulin is used for the primary treatment in T1DM . Insulin is used in all types of DM and has no specific maximum dose. Insulin is the primary treatment in T1DM, and injected amylin can be added to decrease fluctuations in blood glucose levels. Insulin is available in various formulations. Most formulations are available as U-100 , indicating a concentrations of 100unit/mL. Types: Insulin is divided into two main classes:                 1. Basal Insulin                                                                             2. Bolus insulin Storage : Insulin is typically refrigerated, and most vials are good for 28 days at roo

 PHARMACOTHERAPY: Medications classifications include:  Sulfonyl Urea's Nonsylfonylurea Secretagogues (a-Glinides) Biguanides Thiazolidinediones a-Glucosidase Inhibitors Dipeptidyl Peptidase-4 Inhibitors (Gliptins) Sodium-glucose co-transporter (SGLT) Inhibitors  Central-Acting Dopamine Agonists Bile Acid Sequestrants Insulin therapy 7.SODIUM-GLUCOSE CO-TRANPORTER (SGLT-2) INHIBITORS The drugs approved include Canagliflozin, Dapagliflozin, Empagliflozin . Mechanism of Action: Glucose is freely filtered buy the kidney glomeruli and is reabsorbed in the proximal convoluted tubules by the action of sodium glucose co-transporters (SGLT). SGLT accounts for 90% of the glucose reabsorption and its inhibition causes glycosuria in people with diabetes, lowering plasma glucose levels. Dose: Canagliflozin: 100 & 300mg - 100mg daily if usual dose. 300mg daily can be used if eGFR resulting in lowering HDL.  Dapagliflozin: 3 & 10mg - 10 mg daily. 3mg daily in hepatic failure. Empaglifl

  PHARMACOTHERAPY:  Medications classifications include:  Sulfonyl Urea's Nonsylfonylurea Secretagogues (a-Glinides) Biguanides Thiazolidinediones a-Glucosidase Inhibitors Dipeptidyl Peptidase-4 Inhibitors (Gliptins) Sodium-glucose co-transporter (SGLT) Inhibitors  Central-Acting Dopamine Agonists Bile Acid Sequestrants Insulin therapy 5. a-GLUCOSIDASE INHIBITORS Acarbose and Miglitol are a-glucosidase inhibitors currently approved in the United States. Mechanism of Action: An enzyme that is along the brush border of the intestine cells called a-glucosidase; breaks down the complex carbohydrates into simple sugars, resulting in absorption. The a-glucosidase inhibitors work by delaying the absorption of carbohydrates from the intestinal tract, which reduces the rise in postprandial glucose levels. Therapy: As a monotherapy , a-glucosidase inhibitors primarily reduce post-prandial glucose excursions.  Clinical Use: FPG concentrations have been decreased by 40-50mg/dL and A1c level

  PHARMACOTHERAPY: THIAZOLIDINEDIONES Commonly referred to as TZDs or Glitazones , Thiazolidinediones have established a role in T2DM Therapy. Mechanism of Action: TZDs are known to increase insulin sensitivity by stimulating peroxisome proliferator-activated receptor gamma (PPAR-g). Stimulation of PPAR-g results in a number of intracellular and extracellular changes including increased insulin sensitivity and decreased plasma fatty acid levels. Pharmacokinetics: The onset of TZDs is delayed for several weeks and require up ton 12 weeks before maximum effects are observed. Therapy: As monotherapy , TZDs reduce FPG levels by around 60-70mg/dL and the effect of A1c is up to 1.5% reduction. Clinical Uses: Pioglitazone and Rosiglitazone increases HDL . Pioglitazone increases HDL by 5.2mg/dL Rosiglitazone increases HDL levels by 2-4mg/dL. Pioglitazone decreases serum Triglyceride s by an average of 51.9mg/dL. Rosiglitazone increases serum triglycerides. Pioglitazone increases LDL levels

 PHARMACOTHERAPY 2.NONSULFONYLUREA SECRETAGOGUES (GLINIDES) Although producing the same effects as sulfonyl ureas, Non sulfonylurea secretogogues also referred to as Glinides or Meglitinides have rapid onset and short duration of action. Mechanism of Action: Glinides produce a pharmacological action by interacting with ATP-Sensitive potassium channels on the beta cells; however, this binding is to a receptor adjacent to those with which the sulfonyl ureas bind. Clinical Uses: The primary benefit is in reducing post-meal glucose levels. These agents have resulted in a reduction of 0.8-1% A1c levels. Indications: Because they have a rapid onset of action, Glinides are supposed to be taken 15-30 minutes before the meal. Therapy: They may also be used in combination therapy with other drugs to achieve synergistic effects. Combinations with Biguanides is mostly used. 3.BIGUANIDES Biguanides include Metformin as the Drug of choice for T 2 DM. Mechanism of Actions: Biguanides are thought to

  PHARMACOTHERAPY Oral and injectable agents are available to treat patients with T2DM who are unable to achieve glycemic control through meal planning and physical activity. Medications classifications include:  Sulfonyl Urea's Nonsylfonylurea Secretagogues (a-Glinides) Biguanides Thiazolidinediones a-Glucosidase Inhibitors Dipeptidyl Peptidase-4 Inhibitors(Gliptins) Sodium-glucose co-transporter (SGLT) Inhibitors  Central-Acting Dopamine Agonists Bile Acid Sequestrants Insulin therapy SULFONYL UREAS Sulfonylureas represent the first class of Oral blood glucose lowering agents approved by the United States. These drugs are classified as either First- or Second-Generation drugs . Both classes of sulfonyl ureas are effective when given at equipotent doses. Mechanism of Action Sulfonyl ureas enhance insulin secretion by blocking ATP-sensitive potassium channels in the cell membranes of pancreatic beta cells. This action results in membrane depolarization, allowing the influx of cal

  NON PHARMACOLOGICAL THERAPY  MNT Glycemic Index Dietary supplements Weight measurements Physical Activity Psychological assessment Immunizations 2.GLYCEMIC INDEX " The Glycemic index of a carbohydrate containing food is determined by comparing the glucose excursions after consuming 30g of test food with glucose excursions after consuming 50g of reference food (white bread) " Glycemic Index= Blood glucose area under the curve (3hr) for test food / Blood glucose area under the curve (3hr) for reference food Low glycemic index foods have value of 53 or less and include many fruits, vegetables, grainy breads, legumes, etc. High glycemic index foods have value of 70 or greater and include baked potatoes, white bread, etc. 3.DIETARY SUPPLEMENTS Patients may seek and use dietary supplements in the treatment of diabetes.  Remember, despite the popular notion, there is no "diabetes specific diet". Data from randomized controlled trials seem to support the efficacy of Coc