Moving on to management of Type 2 DM, what is the preferred first agent?
–initiated at or soon after diagnosis
Diet and Exercise can improve HbA1c values among patients with type 2 DM
When is it justified to start directly with a combination of two non insulin agents or with insulin itself?
Patient with high HbA1c have a low probability of achieving HbA1c goals with monotherapy
–therefore this therapy is initiated
If a patient presents with significant hyperglycemic symptoms and/or has very elevated plasma glucose concentrations or Hb1Ac what is done?
Insulin therapy should be strongly considered from the outset
–insulin therapy becomes mandatory when catabolic features are exhibited
If metformin is contraindicated what can be used?
Another oral agent
–sulfonylurea, pioglitazone or sitagliptin
If monotherapy does not achieve an HbA1c target over 3 months, what is the next step?
Add a second oral agent, a GLP-1 receptor agonist or basal insulin
–higher Hb1Ac the more likely insulin will be required
If the two drug combination fails to achieve the glycemic target a third agent can be added. What is this?
At this point, the most robust response will usually be with insulin
–many patients will eventually need to be placed on insulin
Transition should be favored when HbA1c is greater than 8.5%
Insulin is typically begun at a low dose with a single injection of basal insulin…?
Either NPH, glargine or detemir insulin
–dose is then uptitrated
If significant postprandial glucose excursions occur the patient will require the addition of prandial insulin therapy with shorter acting insulin
What is the most effective agent of diabetes medications in lowering glycemia?
—decrease any level of elevated HbA1c close to or to therapeutic goals
Moving on to the prevention and management of diabetes complications. CVD is a major cause of morbidity and mortality for individuals with diabetes. Explain the various CVD conditions
- HTN: ACEI or an ARB
- Dyslipidemia: statin therapy should be added to lifestyle therapy, regardless of baseline lipid levels
- Antiplatelet Agents: Aspirin therapy should be considered a primary prevention strategy in patients with type 1 or type 2 diabetes at increased CVS risk
What can be done for nephropathy and diabetes?
ACEI or ARBs are recommended for the treatment of patients with elevated urinary albumin excretion
Moving on to Neuropathy and diabetes, what are some of the complications?
Distal Symmetric Polyneuropathy (DPN): neuropathic drugs include amitriptyline, gabapentin, pregablin, duloxetine, venlafaxne, valproate, and opioids
Gastroparesis: symptoms may improve with dietary changes and prokinetic agents such as erythromycin and metoclopramide
Erectile Dysfunction: tx includes phosphodiesterase 5 inhibitors, prostaglandins, vacuum devices or penile prostheses
Foot Care: polymicrobial aerobic gram positive cocci (Esp staph)
In regards to Insulins what is the pregnancy category for these drugs?
Insulin Lispro and Aspart: B
Regular Insulin: B (DOC for glucose control)
NPH insulin: B
Insulin Glulisine, glargine, and detemir: C
In regards to non insulins what is the pregnancy category for these drugs?
Metformin: B Meglitinides: C Thiazolidinediones: C Sulfonylureas: C Exenatide: C Sitagliptin: B Pramlintide: C
Finally lets touch on Glucagon. It is synthesized by the pancreatic alpha cells consisting of 29 AA. What are the metabolic effects of Glucagon?
Binds to specific receptors on the liver cells
–this leads to Gs protein couple increase in adenylyl cyclase activity and production of cAMP – this leads to catabolism of stored glycogen and increases gluconeogenesis and ketogenesis
Pharmacologic amounts of glucagon cause release of insulin from normal pancreatic beta cells, catecholamines from pheochromocytoma, and calcitonin from medullary carcinoma cells
What are the effects of glucagon on the cardiac system?
Potent inotropic and chornotropic effects on the heart, mediated by cAMP.
–produces an effect very similar to that of Beta adrenoceptor agonists without requiring functioning beta receptors
What are the effects of glucagon on the smooth muscle?
Profound relaxation of the intestine
What are the uses for glucagon?
- Severe Hypoglycemia: in patients with diabetes treated with insulin
- Radiology of the Bowel: aid to xray visualization of bowel because of its ability to relax intestine
- Beta Blocker Poisoning: reversing the cardiac effects of an overdose of beta blockers because of its ability to increase cAMP in the heart
- Glucagon C peptide Test: c peptide response to IV glucagon administration is a test for residual beta cell function in DM
What are the AR for glucagon?
Transient nausea and occasional vomiting
- -generally mild
- -relatively free of severe AR