Treatments for diabetes

Question 1

Sulfonylureas (glitinides)

Answer 1

• Stimulate beta cells to secrete insulin (require functioning beta cells)
• Bind to K channel in membrane and facilitate closing of channel
• There is also Ca entry via voltage-gates Ca channels
• Overall leads to beta cells that more easily release insulin
• Side effects: weight gain, hypoglycemia
• Meglitinide: act at a different site on K channel, shorter acting and less of a risk for hypoglycemia

Question 2

Biguanides (metformin)

Answer 2

• Decreases hepatic glc production (unknown mechanism) during fasting/posprandial
• Side effects: nausea, diarrhea, lactic acidosis
• Contraindicated in pts w/ Cr > 1.5

Question 3

Glitazones (thiazolidinediones, TZDs)

Answer 3

• Bind to PPAR gamma and lead to increased or decreased transcription of multiple genes in tissues
• Leads to an increase in insulin sensitivity in insulin target tissues (adipose, muscle)
• Side effects: weight gain, edema, CHF, liver failure, bladder CA

Question 4

Alpha-glucosidase inhibitors

Answer 4

• Inhibits the cleavage of disaccharides to monosaccharides on the brush border of intestinal epithelium
• This slows the rate of absorption of carbs and diminishes postprandial hyperglycemia

Question 5

GLP-1 (incretins) or DPP4 inhibitors

Answer 5

• DPP4 breaks down GLP1, thus can have the same effect as exogenous GLP1
• GLP1 causes increased insulin secretion, delays gastric emptying, and promotes beta cell neogenesis/decreases beta cell apoptosis
• Promotes satiety and decreases hepatic glc output (decreases glucagon)
• Side effects: nausea

Question 6

Treatments for different types of diabetes

Answer 6

• Only type 2 diabetes can be treated w/ oral meds (T1 must be treated w/ insulin)
• This is b/c oral meds rely on at least some functioning endogenous insulin
• Peripheral insulin resistance: tissues can’t take up glc in response to insulin
• Central insulin resistance: liver won’t stop producing glc in response to insulin

Question 7

How surgeries work

Answer 7

• Decrease appetite possibly from decreased ghrelin release
• Increased satiety
• Decreased absorption (a minor role): only in biliopancreatic diversion and duodenal switch
• Altered release of GI hormones: GLP1 increased

Question 8

Commonly used surgeries

Answer 8

• Lap band (restrictive): rare now, there is diabetes remission after weight loss
• Sleeve gastrectomy: remove the fundus and a large portion of the body of the stomach
• Roux-Y gastric bypass: small bowel connected to the top-most part of the stomach, and the duodenum is connected to the small bowel (malabsorptive)
• There’s diabetes remission before weight loss
• Biliopancreatic diversion w/ duodenal switch: beginning of duodenum is connected to jejunum close to the large bowel (bypasses most of the small bowel)

Question 9

Selecting a pt for surgery

Answer 9

• BMI 35-39 w/ co-morbidity of obesity (DM), must exclude hypothyroidism
• <60 yo, must have non-damaged lungs/heart
• Psychologic evaluation important

Question 10

Outcomes of surgery

Answer 10

• Good: weight loss, reversal of DM, can cure sleep apnea
• Bad: complications such as PE, infection, hemorrhage, malnutrition
• Rare: repetitive vomiting can cause thiamine deficiency and lead to wernicke’s encephalopathy