March 29, 2007

March 29, 2009 Endocrine Medications – Melatonin and Diabetes  How does melatonin work o Darkness releases melatonin from pineal glands o Rises in mid-evening o Secretion decreases in morning o If disturbed – have imbalances in melatonin secretion and will effect sleep wake cycle  Uses of Melatonin o If going westward more helpful (traveling)  Adverse Reactions and Precautions o Associated with vivid dreams and nightmares o Could disrupt circadian rhythms  Drug Interactions o Might cause harm in patients taking psychiatric meds o Might have an interaction with warfarin  Warfarin already has a narrow therapeutic index  Melatonin causes INR to increase, which causes increased risk for bleeds  What is Diabetes? o All related to insulin  Normal Physiology o Helps metabolize glucose for energy o Within our body the pancreas is always secreting insulin  Laboratory Findings o Too much glucose  diabetes o Sometimes diagnosed with patients coming in presenting with symptoms o Self-monitoring – glucose meters at home  Diabetes – Assessment o Not many differences in monitors w.r.t accuracy o Repeat on for the second time to confirm measurements  Diabetes Management o Diet and Exercise  Exercise plays a large role in the management of diabetes  Diabetes Mellitus o Type 1  Normally occurs earlier on w.r.t age  Not sure what exactly causes it  Pancreatic beta cells decline in function and eventually cannot produce insulin  Over time from birth – get a decrease in insulin releae

 When about 20% left in body – get overt symptoms  Goals of Insulin Therapy o Mostly use human sources now o Two main companies that develop insulin – Humulin and Novolin  Types of Insulin o Some combination therapies that help patients o 30/70 is the longer acting  Insulin Glargine – Lantus o Been available for about 2 years o Long acting – 24hrs typically o Beneficial – very smooth o Cross out - >17 years  Comparison of Insulins o Patients take insulin to help control the glucose surge after they eat  Insulin Administration o Subcutaneous – main way  Absorbed through tissue o Intravenous  Admitted into hospital  Pump – in the picture • Continually releases short-acting insulin and when eat, they can change • People not skillful enough to use  Penfill/Cartridge  Inhalation • Need to take a lot more for it to take effect • Not in Canada yet  Factors that may alter Blood Glucose Control o Physical Activity  Diminishes demand o Insulin injection technique  People may not be using technique properly  If always injecting in same spot, then skin atrophies and not able to absorb as well o Inactive insulin  If open too long  Need to store in fridge  Insulin regimens o Varies  Determining factor – depends on conversation between physician and patient about what is manageable o Intensive vs. conventional

With more injections per day and higher control have decreased risk for CV effect, neuropathy, etc  Needs to fit into their daily regiment  Depends on lifestyle (eg. Elderly person who cannot do it themselves, has to wait until someone can come by and do it Sample Insulin Regimens o Dual effect of having 30/70 combo o Try to match meals and lifestyle o If have 3 injections per day  May provide patient with better sugar control  The peak occurs at breakfast instead of the middle of the night Complications/Adverse effects of Insulin Therapy o Hypoglycemia  if under stress/exercise/not enough calories may have hypoglycemia o Fat hypertrophy  If inject into the same site  Goes away if leave the injection site for about a week or so o Allergic reactions  A lot less frequent o Insulin resistance  Need to keep a close eye, can use another agent to make insulin work better Symptoms of hypoglycemia o Confusion  More advanced state o If a diabetic patient run into hypoglycemic attacks it’s important for those around him/her knows how to manage that patient Treatment for hypoglycemia o Need to identify symptoms o Most diabetics will tell you how they feel when blood sugar level low Type 1 Case o DM is a newly diagnosed 22 y.o active female diagnosed with type 1 diabetes o What type of things should you educate this patient about?  Have meal plans  How to manage insulin during meals o What type of therapy might you initialize in her?  Insulin pump  3 short acting and one long acting  4 injection regiments had better outcome o Pt was started on Humulin 30/70 20 units before breakfast at dinner  Regular release insulin is 6 











Day Mon Tues Wed





 









o She comes to clinic reporting the following blood glucose levels from her machine at home Date 7am Noon 6pm 10pm 2/20 9 8.4 14.8 9.8 2/21 6.9 6.2 11.3 9.4 2/22 7.1 7.6 15.9 13.2

o What do you think of this patient’s BS levels?  Need to give more at noon  Didn’t give enough of the long acting insulin  At suppertime not having enough so have more at breakfast or lunch  If get better sugars at 6pm then better at bed time  Can do double step increase at both doses  Can switch to 20/80 if this becomes to low • If switch to 20/80 in morning and 30/70 at night, not as comfortable for patient Clinical features of diabetes at diagnosis o Weakness/fatigue  More common with type 1 o Weight loss  Type 2 usually more obese Treatment of Type 2 DM o Exercise play a huge role o If doesn’t work can look at some of the oral agents First vs. Second Generation o Second generation much more powerful Tolbutamide o Not seen too often o Safe in KI disease Chlorpropamide o Accumulation in KI disease o Fallen out of favour Glyburide o M/c’ly seen in practice b/c covered by Ont. Gov’t o Not necessarily the best Adverse effects of Sulfonylureas o Hypoglycemia may occur  Important to know which ones cause hypoglycemia and which ones don’t o If have sulfa allergies – can get dermatological reactions o Not good drug to take if already obese b/c of weight gain Drug Interactions with Sulfonylureas









o When start or stop these medications keep BS in check Biguanide – Metformin o Come into favour b/c associated with weight loss o Main effect is to decrease hepatic output o A/E  Lactic acidosis (main a/e)  If have renal failure not able to clear out lactic acidic can lead to metabolic acidosis  Can cause a bit of metallic taste  Metallic taste • Don’t enjoy food anymore b/c of metallic taste • May contribute to the weight loss o Drug Interaction  Can’t have alcohol as much b/c increases risk of lactic acidosis  The more metformin in your body the greater chance of acidosis  Regular check for anemia to make sure they are not deficient Acarbose o Takes the glucose from the meal and slows the absorption from the food into the bloodstream o Slower absorption of glucose o More last-line to treat DMII o b/c it slows down food, has to be taken with first bite of meal o has to be committed to taking it o can be monotherapy but it’s last-line o A/E  GI type of effects – diarrhea and flatulence • Very uncomfortable for patient • Usually fall out of favour of taking  Some possibility of liver toxicity Thiaazolidinediones o MOA  Similar to metformin  Sensitize tissue to insulin and helps to decrease hepatic output of insulin  Can use it on it’s own or with other agents o A/E  Weight gain • Patients are obese, so this might be a problem  Increase of HDL (yeah!) but increase TG as well (boo!)  Main side effect – can cause edema • Concerned in using TZD in patients with congestive heart failure Repaglinide



   

 





o Efficacous in decreasing HGA1c o Similar to sulfonyleuras  taken mostly once or twice a day o more frequent with dosing o can be used as monotherapy or on it’s own o A/E  Hypoglycemia  Weight gain  H/A o Drug Interactions  CYP substrate • Can cause hypoglycemic effects as well • If have an inducer – increases excretion (less drug) • If have inhibiter – decreases excretion (more drug) Sites of Action for Oral Therapies for Type 2 Diabetes o Puts pictorially what you can combine and what can combine o Evidence the Metformin and TZD (even though work the same way), they enhance each other’s performance when put together o Rather than maximizing Metformin or TZD get more ‘bang for buck’ if use combination therapy Management of hyperglycemia in type 2 diabetes o Exercise! Hypoglycemic Herbs o Commonly used Hyperglycemic Herbs o Monitor for blood sugars Diabetes and Other Naturopathic Medicine o Metformin and B12 decrease absorption – increased risk for anemia o Metformin and Guar Gum – inhibits absorption of Metformin o Stinging nettle NOT stinging needles UKPDS (1998) Ocular Complications o Yearly check-ups with opthamologist o Leading cause of blindness Nephropathy o End-stage KI disease – linked to diabetes o Have more patients that are developing end-stage renal disease o Ongoing problem o Screening for nephropathy Hypertension o Occurs more frequently in diabetics than non-diabetics o Tx for HTN – drugs, diet (decrease salt), BP monitoring (b/c silent disease)

 Cardiovascular Disease o Deaths b/c end up with advanced glycosylated end products o Lipid abnormalities (put at end of slide)  Peripheral Vascular Disease o Can lead to a lot of pain o Poor circulation to feet – can’t sense b/c of neuropathy o Can’t sense it as much and get ulcers o Treat with Ab, if don’t clear – amputation o Therefore need to be aggressive! o If advanced  need to go for surgery  Neuropathy o Two types  Autonomic • Gastroparesis o After eating not digesting their meal o Bloated feeling o Sometimes complain about gas, but more of a full feeling o Metoclopramide  Helps with gastric motility o Erythromycin  Get bad GI effect  so clears things out  Peripheral • Some people don’t even know they have it b/c can be mild • With peripheral neuropathy will have pins-and-needles in fingertips • Sometimes gets very sharp and unbearable • Typically narcotics are not helpful for this type of pain • Tricyclic anti-depressents o Get side effects – dry mouth, constipation, sedation o Can only increase dose so far b/c not tolerated by patients • Other agents o Gabapentin – used for seizures  Drug of choice, but often people can’t afford it  If elderly and don’t have finances, gov’t doesn’t support  Type 2 Case o Mr. BG is an obese individual newly diagnosed with Type 2 diabetes. He has a past hx of hypercholesterolemia. He is prescribed glyburide 5 mg PO BID. This HgA1c is 10%

o Are there any recommendations that you might want to provide to him or his physician  Diet and exercise  Don’t want additional weight gain  W.r.t. HgA1c • Metformin • Metformin with TZD  Aspirin (hypercholesterolemia)  Ask patient to monitor BS and Blood Glucose levels  Make sure BP is at the most 130/80mmHg