Krisa Christian MD

Diabetes

1 in every 14 Americans has diabetes The disease accounts for 200,000 deaths,

82,000 amputations, 44,400 cases of ESRD, and 24,000 cases of blindness

National Health and Nutritional Examination Survey (1999-2000) found that only 7 percent of adults with diabetes achieved glycemic, lipid, and blood pressure goals

Diagnosis

fasting BG 2 hr Oral GTT

no diabetes <100 mg/dL <140

Prediabetes100 – 125 140 – 199

Diabetes >126 200

The American Diabetes Association recommends which of the following to reduce macrovascular disease?:

a. ASA 75 – 162mg daily b. Blood pressure controlled to 130/80

mmHg or less with an ACE-I c. Achieve an LDL of 130 mg/Dl or less d. Smoking cessation

Macrovascular disease

Atherosclerosis

Aspirin Therapy

ASA 75 – 162mg per day for secondary prevention in diabetics with a history of CAD, MI, CVA or TIA, claudication or PVD, angina

ASA 75 – 162mg per day for primary prevention in any diabetic with an additional CV risk factor

Not recommended for under 21 yrs (Reye’s syndrome)

***United States Physician’s Health Study

Blood pressure control

Minimal incidence of complications when BP < 130/80 mm Hg, even lower with nephropathy Generally recommend treatment with low-

dose thiazide for diabetics with HTN, unless there is an indication for another antihypertensive agent

*** ALLHAT trial, JAMA 2002

Lipid Control

In a diabetic patient, goal lipid control is defined as which of the following?: A. LDL <100 mg/dl B. HDL > 50 mg/dl C. Triglycerides < 150 mg/dl D. All of the above

Glycemic Control

In a diabetic patient, goal A1C value is which of the following?: A. <7 percent B. <6.1 percent C. 80 – 150 mg/dl D. depends on the age/circumstance of the

patient

A1C

A 1% change in an A1c result reflects a change of about 30 mg/dL (1.67 mmol/L) in average blood glucose. For instance, an A1c of 6% corresponds to an

average glucose of 135 mg/dL (7.5 mmol/L), while an A1c of 9% corresponds to an average glucose of 240 mg/dL (13.5 mmol/L).

The closer a diabetic can keep their A1c to 6%, the better their diabetes is in control. As the A1c increases, so does the risk of complications.

Glycemic Control

Intensive therapy aimed at improved glycemic control reduce the rates of microvascular complications: Neuropathy Nephropathy Retinopathy

Glycemic Control

How often should you check a hemoglobin A1C? A. Every 3 months B. Twice yearly C. Once yearly D. Only if you are unaware of the patient’s

average blood glucose reading

Secretion of Insulin

Pancreatic beta cell hormones Insulin Amylin

Pancreatic alpha cell hormones Glucagon

Gastrointestinal peptides Glucagon-like peptide - 1 Gastric inhibitory peptide

Treatment

For a type II diabetic, the best initial treatment includes which of the following?: Biguanides Sulfonylureas Thiazolidinediones Alpha-glucosidase inhibitors Amylin and GLP-1 based therapies Insulin

Oral Medications (insulin sensitizers)

Biguanides METFORMIN

Effective only in the presence of insulin Major effect is to increase insulin action

Possibly by suppressing hepatic glucose output Increased insulin-medicated glucose utilization in

peripheral tissues Antilipolytic effect that lowers serum free fatty acids,

reducing substrate availability for gluconeogenesis

Oral Medications, cont

METFORMIN Promotes modest weight reduction or at least

weight stabilization Lowers fasting blood glucose concentrations

by at least 20 percent

Oral Medications, cont METFORMIN

Less likely to cause hypoglycemia (does not increase insulin secretion)

Has prominent lipid lowering activity (decreases serum TG and free fatty acid concentrations, small decrease in LDL, increase in HDL)

Disadvantages ---1. Risk of lactic acidosis (esp with radiologic procedures involving contrast material – hold metformin for 48 hours following)2. Gastrointestinal side effects (metallic taste, mild anorexia, nausea, abdominal discomfort and diarrhea).3. May decrease absorption of vitamin B12 by 30% but rarely

causes megaloblastic anemia.4. Avoid if renal or hepatic impairment or NYHA class III or IV HF

Oral Medications (insulin sensitizer)

Thiazolidinediones (Pioglitazone) Increase insulin sensitivity by acting on liver

and muscle to increase glucose utilization and decrease glucose production

Monotherapy or combination More expensive Side Effects: potential hepatotoxicity (,weight

gain (can be substantial), fluid retention (may precipitate CHF)

Oral Medications (Insulin sensitizer)

Alpha-glucosidase inhibitors and lipase inhibitors (acarbose and miglitol) Inhibit gastrointestinal enzymes that convert

carbohydrates into monosaccharides in a dose-dependent fashion

Slow absorption of glucose (decreases post-prandial hyperglycemia)

Potentially benefit type 1 and type 2 diabetes

Oral Medications

Alpha-glucosidase inhibitors Acarbose 100mg TID showed benefit on

LDL/HDL ratios Side effects are flatulence (73% vs 39%

placebo) – may be less with slow increases in dosage.

Oral Medications (insulin secretagogues)

Sulfonylureas Stimulates insulin secretion from the

pancreatic beta-islet cells Useful only when beta-islet cell function

exists. Suppress overnight hepatic glucose output Lower blood glucose concentrations by about

20% (similar to a once or twice daily long acting insulin)

Oral Medications

Sulfonylureas Side Effects

Hypoglycemia especially with longer acting sulfonylureas (chlorpropamide, glyburide)

Nausea Weight gain Skin reactions Abnormal LFTs Specific to chlorpropamide –flushing reaction when used

with alcohol, hyponatremia (SIADH) Best to avoid if renal disease, elderly or infrequent mealtimes

Oral Medications

Meglitinides Structurally different than sulfonylureas but

act similarly to regulate ATP-dependent potassium channels in pancreatic beta-cells to increase insulin secretion

Repaglinide (Prandin) Nateglinide (Starlix) Sometimes used if infrequent meals, renal

disease, or post-prandial hyperglycemia

Oral Medications (novel therapies)

Dipeptidyl Peptidase IV inhibitors Sitagliptin (Januvia) and Vildagliptin (pending

FDA approval) DPP IV = the enzyme that degrades

endogenous secreted incretins (GLP-1 and glucose-dependent insulinotropic polypeptide

Lead to increased secretion and suppression of glucagon secretion

Oral medications, cont

DPP IV inhibitors Are weight neutral Does not cause hypoglycemia Drawbacks:

Remember to reduce dosing in patients with renal insufficiency

Side effects include nasopharyngitis and headache

A 56 year old with type II diabetes is scheduled to undergo a diagnostic angiogram following a positive stress test. Which of the following medications should be held prior to the angiogram?

A. Lisinopril (ACE-I) B. Simvastatin (statin for cholesterol

therapy) C. Metformin (biguanide for diabetes) D. Insulin E. ASA

A 42 year old male comes in for his annual physical. He reports only increased fatigue as of late.VS – weight 323#, height 6’2’’bp 142/84, p 86exam remarkable only for morbid obesityfasting glucose of 260, a1c 9.1% urine microalbumin is negative

You make the diagnosis of diabetes type II and start: A. Metformin 500 mg at night, titrating up

as tolerated B. Hydrochlorthiazide 12.5mg daily C. ASA 81mg daily D. Insulin 70/30 10 units SQ in the

morning and at night

Subcutaneous medications

Pramlintide (Amylin analog) Decreases rate of gastric emptying Suppresses glucagon secretion (and hepatic

glucose production) Promotes satiety (decreases appetite)

Less hypoglycemia, some weight loss

Approved for type I

Subcutaneous medications

Exenitide (synthetic exendin-4, a peptide with GLP-1 like actions) Slows gastric emptying Supresses inappropriately elevated glucagon levels Insulinotropic (augments insulin secretion), a dose

dependent and glucose dependent phenomenon Not currently approved for use with insulin therapy

Subcutaneous medications

Insulin Stimulates glucose uptake in muscles and fat Inhibits lipolysis Promotes glycogen deposition Enhances protein synthesis

Insulin Dosing range and Average Daily Dosing

Multiple daily injectionsInitial dose Average total daily dose

Type I DM 0.2 U/kg/d 0.4 – 0.6 U/kg/d

Type II DM 0.3-0.5 U/kg/d 0.8 – 1.2 U/kg/d

Pre meal sliding scale insulin adjustment of mealtime insulin

THE 1800 RULE

1800/total daily insulin dose = mg/dl that 1 unit of insulin will decrease blood glucose Example – if our patient requires 50 units per

day 1800/50 = 36 That means that 1 unit of insulin will decrease BG

by 36 units If pre-prandial blood glucose is 150, you may want

to give the patient 1 Unit of shorter acting insulin to decrease her blood sugar to a goal of 110.

Treatment For a type I diabetic, treatment should

include which of the following?: A. Basal dose of insulin with pre-meal

bolus (intensive therapy) B. Continuous SQ insulin infusion (insulin

pump) C. Oral agents D. Diet therapy

A 65 year old female with type II diabetes and CHF is not achieving adequate blood glucose control. She is taking maximum doses of metformin and glimepiride. Which diabetic agent could you add to help improve

her A1C? A. Rosiglitazone B. Simvastatin C. Exenetide D. Insulin

A 17 year old man develops polyuria, polydipsia and rapid weight loss. He comes to see you in your clinic and you run some labs, only to discover the following:

Serum sodium 132 mmol/L (normal is 135 – 140)

Serum potassium 5.3 mmol/l (normal is 3.6 – 5.4)

Serum glucose 416 mg/dL (normal is 70 – 100)

 He is not acidotic and shows no signs of infection.

You diagnose Type I diabetes melitus and decide to start insulin.

A good starting range would be:

a.       0.2 U/kg/d b.      1 unit for every 100 mg/dL his blood

glucose is above 100 c.       0.5 U/kg/d d.      10 units twice a day e.       you opt to start him on oral

medications instead

The 1800 Rule helps you to:

a. Calculate the amount 1 unit of insulin will decrease BG based on the patient’s usual daily dosing

b. Calculate the total amount of insulin needed for a new patient starting on insulin

c. Calculate body mass indexd. Assign a schedule of insulin based on military

timee. Calculate the amount of fluid needed for a

patient in diabetic ketoacidosis

A good patient to start on insulin would be:

  a. A patient with a pre-meal blood glucose

consistently >250 mg/dl despite oral therapy b. A patient with symptomatic hyperglycemia

(polyuria. polydipsia, weight loss due to dehydration, etc)

c.  All Type I and DM due to pancreatic failure d. Type II not reaching glycemic goals with

nutrition and oral drug therapy