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Diabetes Mellitus

AnnaGolovko

Introduction

Diabetes mellitus (DM) is a group of metabolic disorders characterized by hyperglycemia resulting from defects in insulin secretion, action, or both

DM is associated with abnormalities in the metabolism of proteins, carbohydrates and fats.

DM leads to microvascular and macrovascular complications

Microvascular: retinopathy, nephropathy, and peripheral neuropathy

Macrovascular: coronary heart disease, stroke, and PVD

Epidemiology

DM affects more than 170 million people worldwide By 2010 this number will increase by as much as 50% ~90% of patients with diabetes have type 2 DM ~10% of patients have type 1 DM or other causes of

diabetes Racial and ethnic populations at highest risk for type 2 DM:

African American, Native Americans, Hispanics, Asian Americans, and Pacific Islanders

Cardiovascular morbidity in type 2 DM patients is 2-4 times greater than in non-diabetic patients

Classification of Diabetes Mellitus

Type 1Diabetes Mellitus Average onset is in childhood or early adulthood

(usually before 30 years of age) Characterized by autoimmune destruction of

pancreatic β-cells →absolute insulin deficiency Patients depend on exogenous insulin to sustain

life


Type 2 DM Usually diagnosed after the age of 30 Endogenous levels of insulin may be normal, decreased,

or increased Insulin resistance and insulin tolerance are present in

initial stages Prevalence increases with age, however an increasing

number of adolescents are being diagnosed as a consequence of obesity and sedentary lifestyle


Secondary Diabetes Develops as a result of other disorders or treatments

Diseases of the pancreas: chronic pancreatitisEndocrinopathies:

Cushing’s syndrome: ↑cortisol Acromegaly: ↑growth hormone Thyrotoxicosis: ↑thyroid hormone

Drug induced: glucocorticoids, pentamidine, thiazides


Genetic defects MODY Insulin receptor mutations or post receptor defects Glycogen synthase deficiency Many others

Gestational diabetes (GDM) Onset of glucose intolerance usually in the 2nd or 3rd

trimester 50% chance of ultimately developing to type 2 DM

Impaired Glucose Tolerance (IGT) and Impaired Fasting Glucose (IFG)

Not diagnostic of DM Risk factors for DM and CVD

Table 27-5. The Diabetes Expert Committee criteria for evaluating the standard oral glucose tolerance test.1

NormalGlucoseTolerance

ImpairedGlucoseTolerance

DiabetesMellitus2

Fasting plasma glucose (mg/dL)

< 110 110-125 ≥ 126

Two hours after glucose load (mg/dL)

< 140 ≥ 140 but < 200 ≥ 200

1Give 75 g of glucose dissolved in 300 mL of water after an overnight fast in subjects who have been receiving at least 150-200 g of carbohydrate daily for 3 days before the test.2A fasting plasma glucose ≥ 126 mg/dL is diagnostic of diabetes if confirmed on a subsequent day.

Pathophysiology of Type 1 DM

Immune-mediated destruction of pancreatic β-cells

Certain antibodies detected in blood Islet cell antibody (ICA) Glutamic acid decarboxylase (GAD65) antibody Insulin autoantibody (IAA)

HLA-DR3 and HLA-DR4 as well as DQA and DQB genes are strongly associated with type 1 DM


Environmental triggers Viral infections (mumps, influenza) Early exposure to cow milk (BSA, bovine serum albumin) Environmental toxins Puberty

“Honeymoon” phase →transient remission Hyperglycemia occurs when 80%-90% of β-

cells are destroyed


Multifactorial pathogenesis Genetic mutations Environmental factors

Genetically predisposed patients trigger onset of DM by leading a diabetogenic lifestyle

Over-eating → obesity Lack of exercise a.k.a. sedentary lifestyle


Genetic predisposition Many genes are responsible for causing both β-cell

failure and insulin resistance

Family history Increases risk by >2 times One parent with type 2 DM: lifetime risk of

developing DM is ~38% by age 80 Both parents with DM: risk increases up to 60% by

age 60%


Other Risk Factors for developing type 2 DM HTN (≥ 140/90 mmHg) Hyperlipidemia (HDL ≤35 mg/dL, TGs ≥ 250mg/dL) High risk ethnic groups: African Americans,

Hispanics, Asians W>M


Typical physiological abnormalities in type 2 DM Increased glucose production in the liver Impaired insulin secretion Insulin resistance


Insulin Resistance Strongly associated with obesity and physical

inactivity Due to defect in the expression of GLUT-4

receptor Etiology both genetic and environmental ß-cells produce more insulin to counteract the

resistance resulting in hyperinsulinemia Hyperinsulinemia is associated with HTN,

dyslipidemia, and atherosclerotic vascular disease

Metabolic syndrome A group of related conditions that increase the risk for CVD Characterized by the presence of 3 or more conditions:

Abdominal obesity (waist >40in in men and >35in in women)

Elevated blood pressure ≥130/≥85 mmHg Insulin resistance (FBG ≥100 mg/dL) Dyslipidemia (triglycerides ≥150 mg/dL, HDL <40mg/dL in

men and <50mg/dL in women Proinflammatory state (elevated C-reactive protein, CRP)

~22% of American adults have this syndrome


Symptoms of diabetes and a casual plasma glucose ≥ 200 mg/dlThe symptoms of diabetes include polyuria, polydipsia, polyphagia, ketoacidosis, and unexplained weight loss.

ORFPG ≥126 mg/dl

OR

2-h plasma glucose ≥200 mg/dl after an OGTT (using a glucose load containing the equivalent of 75-g

anhydrous glucose dissolved in water).

Criteria for the diagnosis of diabetes

These criteria should be confirmed by repeat testing on a different day

Screening for Type 2 DMCriteria for testing for diabetes in asymptomatic adult individuals1. Testing for diabetes should be considered in all individuals at age 45 years

and above, particularly in those with a BMI ≥25 kg/m2* and, if normal, should be repeated at 3-year intervals.

2. Testing should be considered at a younger age or be carried out more frequently in individuals who are overweight (BMI ≥25 kg/m2*) and have additional risk factors, as follows:• are habitually physically inactive• have a first-degree relative with diabetes• are members of a high-risk ethnic population (e.g., African American, Latino, Native American, Asian American, Pacific Islander)• have delivered a baby weighing >9 lb or have been diagnosed with GDM• are hypertensive (≥140/90 mmHg)• have an HDL cholesterol level <35 mg/dl and/or a triglyceride level >250 mg/dl • have PCOS• on previous testing, had IGT or IFG• have other clinical conditions associated with insulin resistance (acanthosis nigricans)• have a history of vascular disease

Acanthosis Nigricans A skin disorder characterized by velvety, light-brown-to-black, markings usually on the neck, under the arms or in the groin. Acanthosis nigricans is most often associated with hyperinsulimea

http://www.aocd.org/skin/dermatologic_diseases/acanthosis_nigrica.htmlhttp://dermatology.cdlib.org/DOJvol6num1/original/acanthosis/katz.html

Treatment

Desired outcomes: Reduce risk for microvascular and macrovascular

complications Reduce mortality Achieve glycemic control Improve quality of life

Specific Desired EndpointsGlycemic Control

Hemoglobin A1C <7.0%*

Preprandial capillary plasma glucose 90-130 mg/dL (5.0-7.2 mmol/L)

Peak postprandial capillary plasma glucose** <180 mg/dL (<10.0 mmol/L)

Blood pressure <130/80 mmHg

Lipids***

Low-density lipoprotein (LDL) <100 mg/dL (<2.6 mmol/L)

Triglycerides <150 mg/dL (<1.7 mmol/L)

High-density lipoprotein (HDL) >40 mg/dL (>1.1 mmol/L)****

Key concepts in setting glycemic goals: A1C is the primary target for glycemic control.Goals should be individualized.Certain populations (children, pregnant women, and elderly) require special considerations.Less intensive glycemic goals may be indicated in patients with severe or frequent hypoglycemia.More stringent glycemic goals (i.e., a normal A1C, <6%) may further reduce complications at the cost of increased risk of hypoglycemia (particularly in those with type 1 diabetes).Postprandial glucose may be targeted if A1C goals are not met despite reaching preprandial glucose goals.

http://guidelines.gov/summary/summary.aspx?doc_id=7212&nbr=004306&string=diabetes

Non- pharmacological treatment

Diet Medical nutrition therapy (MNT) is recommended for

all patients with DM The goal is to achieve a reasonable body weight,

reduce postprandial hyperglycemia, reduce cholesterol and TGs, and achieve blood pressure goals

Moderate weight loss of approximately 5% of total body weight can improve FBG in most patients

These goals help reduce the chronic complications of diabetes

Composition of diet

Protein 15%-20% of total calories If microalbuminuria is present:

0.8-1.0 g/kg of protein

If macroalbuminuria is present: 0.8 g/kg

Composition of diet

Carbohydrates Total amount of carbohydrates is more important

than the source and type of starch or sugar Whole grain products, fruits and vegetables should

be included in the diet Carbohydrates should be evenly spaced out

throughout the day as smaller meals and snacks

Composition of diet

Fat <30% of total calories

<10% of calories from saturated fats <10% of calories from polyunsaturated fats 10%-15% of calories from monounsaturated fats

Sodium Sodium intake should be between 1,500-2,400 mg/day

Physical Activity

Aerobic exercise of 20-60 minutes 3-5 times per week has been shown to improve glucose tolerance, improve circulation, lower insulin requirements, and help lose weight

Before any start of exercise program patients should first be evaluated for silent ischemia with a cardiac stress test

Pharmacologic Treatment of Type 1 DM

The primary therapy for type 1 DM is insulin therapy Function of insulin

Stimulates entry of amino acids into cells → enhances protein synthesis

Enhances lipogenesis and inhibits lypolysis and ketogenesis Inhibits hepatic gluconeogenesis Promotes the storage of glucose as glycogen Inhibits formation of glucose from amino acids Promotes generation of NO in vascular endothelial cells


Mechanism of action: Cells take up glucose only by facilitated diffusion

through a group of hexose receptors In most tissues the major transporter is GLUT-4 which

is present in cytoplasmic vesicles When insulin binds to its receptor on the cell surface, it

activates a cascade reaction that result in rapid fusion of GLUT-4 with the cell membrane → glucose is taken into the cell


Exogenous insulins are categorized according to their strength, onset and duration of effect, species source (animal or human), and purity

Three types of insulin available: Beef: differs from human insulin by 3 aa Pork: differs by 1 aa Human: made from recombinant DNA


Pharmacokinetics Half-life of IV: 9 minutes Steady state is reached in 45 minutes Onset of action faster and duration of action shorter for

IV>IM>SQ Rate of absorption fastest from abdomen and slowest from

thigh and buttocks Metabolized in:

Liver: up to 50% is deactivated in the first passage Kidney: 15%-20% Muscle

Type of Insulin & Brand Names Onset Peak Duration

Rapid Acting

Humalog 15-30 min. 30 min to 2½ hours 3-5 hours

Novolog 10-20 min. 1-3 hours 3-5 hours

Short Acting

Regular (R) 30 min. -1 hour 2-5 hours 5-8 hours

Intermediate Acting

NPH (N) 1-2 hours 4-12 hours 18-24 hours

Lente (L) 1-2½ hours 3-10 hours 18-24 hours

Long Acting

Ultralente (U) 30 min.-3 hours 10-20 hours 20-36 hours

Lantus 1-1½ hour No peak time; insulin is delivered at a steady level 20-24 hours

Pre-Mixed*

Humulin 70/30 30 min 2-4 hours 14-24 hours

Novolin 70/30 30 min. 2-12 hours Up to24 hours

Novolog 70/30 10-20 min. 1-4 hours Up to 24

Humulin 50/50 30 min. 2-5 hours 18-24 hours

Humalog mix 75/25 15 min. 30 min.-2½hrs 16-20 hrs

Types of Insulins

http://www.clevelandclinic.org/health/health-info/docs/3300/3376.asp?index=11452


Problems with Insulin Lipoatrophy: loss of fat at injection site due to

antibody formation leading to breakdown of fat in the area of injection (need to rotate sites!)

Hypertrophy: increase in fat mass at the site, the area is anesthetized, however leads to erratic insulin absorption

Resistance: require large amounts of insulin to get desired effect, due to antibody formation


Problems with insulin Hypoglycemia:

Blood glucose < 50mg/dl Symptoms: hunger, palpitations, sweating, fainting Risk factors: age >70, renal insufficiency, excessive

alcohol use, malnutrition Drug interactions: probenicid, allopurinol, aspirin,

sympatholytics Treatment: rule of 15 → 15g of carbohydrates every

15 minutes until BG is greater than 70mg/dl, then follow with a simple meal


Foods that will provide 10g of carbs ½ cup of orange juice or soda Sugar: 2 teaspoons or 2 cubes Glucose tablets: 2-4 tablets Apple juice: 1/3 cup

Foods to avoid Ice cream, candy bars, cookies, cakes

If unconscious: Glucagon 1mg SQ, IM, or IV and Dextrose 50% 50ml infusion

Diabetic Ketoacidosis (DKA)

Diabetic ketoacidosis is usually precipitated by a stressful event such as trauma, infection, surgery or myocardial infarction because these events are usually characteristic of an increased release of cortisol, glucagon, and catecholamines (hormones that stimulate production of glucose and ketoacids).

DKA presents as hyperglycemia (glucose: 250-800mg/dl), volume depletion, high anion gap metabolic acidosis, hypokalemia, glucosuria, urine ketosis (ketones are another source of energy when the glucose pathway is impaired), and hyperosmolality on labs. Patients present with tachycardia, polydipsia, abdominal pain, nausea, vomiting and coma.

Diabetic Ketoacidosis (DKA)

Treatment: Fluid replenishment with normal saline (2-3L over first 3 hours) Insulin continuous infusion (0.1 units/kg) If serum K+ < 4.5 mEq/L, administer Potassium chloride 10

mEq/h Routine use of bicarbonate is not recommended but can be used

in critical patients if their acidosis was not corrected with hydration and insulin

Asses the cause of DKA (trauma, infection, non-compliance with meds)

Patients should be monitored closely


When choosing therapy, the patient’s age, weight, renal and hepatic function should be assessed


Sulfonylureas Increase insulin production in pancreas

Bind to the SU-receptor on cell membrane of pancreatic ß-cells that associated with ATP-dependent K+ channel →depolarization and opening of calcium-dependent channels → increase in calcium causes an increase in insulin secretion

Decrease gluconeogenesis in the liver Improve insulin sensitivity in peripheral tissues

Sulfonylureas

First generation Acetohexamide (Dymelor), chlorpropamide

(Diabinese), tolazamide (Tolinase), tolbutamide (Orinase)

Lower in potency than 2nd generation SUs Have more side effects

Second generation Glimepiride (Amaryl), glipizide (Glucotrol, Glucotrol

XL), and glyburide (Diabeta, Micronase, Glynase)

Sulfonylureas

Who is a candidate: Normal weight type 2 DM patients Onset of DM after age 30 Initial BG < 250mg/dl Relatively normal renal and hepatic function

Who is not a candidate: Pregnant and lactating women Ketosis-prone patients Elderly, debilitated, or malnourished

Sulfonylureas

Pharmacokinetics All SUs are metabolized by the liver Renally eliminated, require dosage adjustments

Efficacy: HgA1c ↓1.5%-2% FBG ↓50-60mh/dl Dose can be increased every 1-2 weeks for glycemic control

Adverse effects: hypoglycemia, weight gain, GI upset

Sulfonylureas

Drug interactions: Clofibrate, phenylbutazone, salicylates,

sulfonamides → displace SUs from protein binding Chloramphenicol, MAOIs, phenylbutazone →

reduce hepatic SU metabolism Allopurinol, probenecid →decrease urinary

excretion of SUs

Sulfonylureas

Glyburide dose: 1.25-10 mg single or divided doses 0.75-12mg (glynase) Half-life: biphasic 3.2 +10 Onset: 1.5 hr Duration: 24hr 50-200 times more potent than other SUs Causes more hypoglycemia than other agents Take on an empty stomach

Sulfonylureas

Glipizide Dose: 2.5-20 mg QD-BID, max dose= 40mg, 20mg (XL) Half-life:3.5-6 hr Onset:1 hr Duration:12-16 hr Once daily dosing available safer in mild renal impairment Minimal weight gain Food has no effect on absorption

Sulfonylureas

Glimipiride Dose: 1-8 mg/day, max=8mg Half-life:~2.5 hr Onset:2-3 hr Duration: 24hr Take with first main meal Indicated for second-line therapy with insulin

Tolbutamide (Orinase) Dose: .25-3.0g divided doses, max=2-3g/day Half-life: 5hr Onset: 1hr Duration:6-12hr Least potent, shortest half-life Preferred in kidney disease

Sulfonylureas

Acetohexamide (Dymelor) Dose: 0.25-1.5g single or divided doses Half-life: 5 hrs Onset: 1hr Duration: 10-14 hrs No advantage over tolbutamide, but was seen to be effective

in patients who failed on tolbutamide Tolazamide (Tolinase)

Dose:0.1-1.0g single or divided, max=1g Half-life:7 hr Onset: 4-6 hr Duration: 10-14 hr

Sulfonylureas

Chlorpropamide (Diabinese) Dose: 0.1-0.5g single dose, max=0.5g Half-life: 35 hr Onset:1 hr Duration: 72 hr Longest duration Cholestatic jaundice and hepatocellular disease

has occurred (rare) Disulfiram syndrome occurred in few cases

Sulfonylureas

Place in therapy Monotherapy for type 2 DM (FBG 140-160mg/dl) Combination therapy (FBG > 160 mg/dl)

Meglitinides

Non-sulfonylurea insulin secretagogues Require glucose to work Also bind the ATP –dependent K= channel to

release insulin Used for management of meal-related glucose

loads Less hypoglycemia than with SUs

Meglitinides

Repaglinide (Prandin) Pharmacokinetics:

Metabolized by Cyt P450 3A4 Half-life: 1 hr Excreted in bile

Dose: 0.5-4mg QID, max 16mg/day, taken 0-30min before meal, if meal is skipped skip the dose as well

Not contraindicated in renal and hepatic insufficiency

Meglitinides

Nateglinide (Starlix) Pharmacokinetics:

Metabolized by P450 2C9 (70%) and 3A4 (30%), inhibitor of 2C9

98% albumin bound Dose: 120mg TID 1-30min before food, 60mg TID can be

given to patients who are close to their HgA1c goal Safe in hepatically impaired and renally impaired patients Synergistic with metformin, decreases HgA1c by 1.5-2.5%

Meglitinides

Efficacy: HgA1c ↓ 0.6%-1%

Adverse reaction Low incidence of hypoglycemia (0.3%) Slight weight gain

Contraindications: Pregnancy, DKA, severe infection, children

Alpha-Glucosidase Inhibitors

Acarbose (Precose) and Miglitol (glyset) Interfere with hydrolysis of carbohydrates and delay

absorption of glucose and monosaccharides in the brush border of small intestine

Efficacy: reduce post-prandial hyperglycemia by about 50mg/dl Reduce FPG by 25-30mg/dl Decrease HgA1c 0.5-1.0% Additive effect with SUs Does not stimulate insulin secretion and will not cause

hypoglycemia if used as monotherapy No weight gain


Adverse effects GI: flatulence, diarrhea, and abdominal pain Elevation in AST and ALT values: dose related and

associated with low weight <60kg Contraindications

DKA Liver cirrhosis inflammatory bowel disease Pregnancy Bowel obstruction SCr >2.0 mg/dl


Can be used in combination with insulin, SU, and metformin

Dose: dose must be slowly titrated up to avoid GI disturbances

Week 1-2: 25mg PO QD Week 3-4: 25mg BID Week 5-6: 25mg TID Maintenance dose: 50mg TID if patient<60kg,

100mg TID if >60kg

Biguanides

Metformin (Glucophage) Antihyperglycemic or insulin sensitizer:

Does not stimulate insulin secretionDecreases hepatic production of glucose Increases glucose utilization by muscle and

adipose tissue (partially reversing insulin resistance)

May also reduce intestinal glucose absorption

Biguanides

Efficacy Reduces FPG by 60-70 mg/dl Reduces HgA1c by 1.5-2.0% Reduction in: TGs by 16%, LDL by 8%, and increases HDL

by 2% Weight loss of 2-5 kg

Adverse effects GI: bloating, nausea, diarrhea, cramping Metallic taste in the mouth Lactic acidosis Hypoglycemia if used in combination with insulin or SU Headache

Biguanides

Contrindications Renal impairment: SCr ≥ 1.5mg/dl for men and

≥1.4mg/dl for women Cardiac or respiratory insufficiency History of lactic acidosis Severe infection Liver disease with abnormal LFTs Alcohol abuse

Biguanides

Drug interactions: Drugs that are eliminated through renal tubular secretion can

potentially interact with metformin such as digoxin, morphine, procainamide, vancomycin, ranitidine

Furosemide and nifedipine can potentially increase metformin plasma concentrations

Dosing: start with 500mg or 850mg QD or BID and titrate slowly up to the

desired effect Increases should be done every 7-14 days Maximum daily dose =2550mg or 2000mg for XR formulation Administer with meals to minimize GI side effects

Biguanides

Metformin is indicated as monotherapy as well as in combination with glitazones, alpha glucosidase inhibitors, meglitinides or insulin

Thiazolidinediones

Glitazones: Rosiglitazone (Avandia) and Poiglitazone (Actos)

Referred to as insulin sensitizers because they increase insulin sensitivity and glucose uptake in muscle and adipose tissue without stimulating insulin secretion

MOA: Glitazones bind to the PPAR gamma receptor in the cell nucleus which stimulates gene transcription responsible for making GLUT-4-R. the GLUT-4 receptor moves to the cell membrane allowing glucose to enter the cell. Other effects: inhibit hepatic gluconeogenesis and redistribution

of fat

Thiazolidinediones

Efficacy Takes 2-3 months to see full effect

Rosiglitazone (Avandia) Decreases: FPG by 30-60mg/dl, HgA1c by 0.8-1.5%, TGs by

7-14% Increases: LDL by 14-18% and HDL by 11-14%

Pioglitazone (Actos) Decreases: FPG by 39-65mg/dl, HgA1c by 1.0-1.6%, TGs by

5-26% Increases: HDL by 6-13%

Thiazolidinediones

Adverse effects Serum transaminase elevations: baseline LFTs should be

obtained and repeated every other month for the first 12 months and periodically thereafter. Drugs should not be started if baseline AST or ALT levels are greater than 2.5 times the normal and they should be stopped if AST and ALT are greater than 3 times the norm or if signs and symptoms of liver injury are present

Fluid retention Weight gain Hypoglycemia if combined with other agents

Thiazolidinediones

Drug interactions Rosiglitazone is metabolized by Cyp2C8 and 2C9 Pioglitazone is metabolized by Cyp2C8 and 3A4

Pioglitazone induces 3A4: decreased plasma concentration of OCs

Inhibitors of 3A4 will increase pioglitazone concentrations

Thiazolidinediones

Pioglitazone and rosiglitazone are both indicated for monotherapy and in combination with SU, meglitinide, metformin or insulin

Doses: Rosiglitazone :4-8 mg/day as a single dose or two

divided doses Pioglitazone: 15-45mg/day as a single daily dose

Exenatide (Byetta)

Approved as an alternative for starting insulin therapy in type 2 diabetics who were not adequately controlled with metformin, a sulfonylurea or both.

MOA: Amino acid sequence similar to human glucagon-like peptide-

1(GLP-1) Stimulates insulin secretion in the presence of glucose Lowers serum glucagon concentrations Slows gastric emptying Increase satiety

Exenatide (Byetta)

Promotes weight loss Improves HgA1c values (decrease in 1.1%

from baseline) Starting dose of exenatidine is 5mcg SC

BID at any time before the morning and evening meals

Medications that all diabetic patients should be on Aspirin (81-325mg/day) Statin ACEI Beta-blocker Thiazide diuretic

Monitoring /Counseling Assess nutrition and physical activity regularly Monitor HgA1c every 3-6 months Lipid profile yearly Blood pressure each visit Alcohol and smoke cessation Thorough annual physical exam Self-Monitoring Blood Glucose Foot care Annual dilated eye examination Renal assessment for microalbuminuria Cardiovascular complications Influenza vaccine yearly Pneumococcal vaccine every 5 years Assess for peripheral neuropathy and PVD Retinopathy

Patient caseAD is a 70 y/o white male who presented to the ER

with worsening SOB on exertion PMH: HTN, Dyslipidemia ( 8/15/05 Tchol=166mg/dl,

TGs=153mg/dl, HDL=29.3mg/dl, LDL=106mg/dl), BPH, Gout, type 2 DM (HgA1C=7.6mg/dl from 8/05)

SH: smokes 1 cigar/day. Used to smoke 8-9 cigars/day > 20 yrs, cut down several years ago.

-- ETOH -- IVDA

FH: Mother and Father --> DM

Vital Signs: Pulse: 88bpm CrCl ~62ml/min Respiration: 24bpm Temperature: 98 F Weight: 227 lb [103.2 kg] Height: 71.5 in BP: 148/64mmHg Labs: GLUCOSE 193.0 H mg/dl UREA NITROGEN 43.0 H mg/dl CREATININE 1.2 mg/dl SODIUM 134.1 L mmol/L POTASSIUM 5.2 H mmol/L PROTEIN, TOTAL 6.2 L gm/dl ALBUMIN 3.9 gm/dl TOT. BILIRUBIN 1.4 H mg/dl ALKALINE PHOSPHATASE 39.0 L U/L SGOT 31 IU/L SGPT 20.0 U/L FINGER STICK GLUCOSE 235 H mg/dl

GLUCOSE 193.0 H mg/dl GLUCOSE 240.0 H mg/dl

Current medications: ALLOPURINOL TAB 100MG PO QD ASPIRIN (ENTERIC COATED) TAB,EC 81MG PO QD ENOXAPARIN NA (LOVENOX) INJ 40MG/0.4ML SC QD

GEMFIBROZIL TAB,ORAL 600MG PO BID NIFEdipine (ADALAT CC) TAB,SA 5MG PO QD ROSIGLITAZONE (AVANDIA) TAB 4MG PO BID SIMVASTATIN (zoCOR) TAB 20MG PO QHS TERAZOSIN HCL (HYTRIN) CAP,ORAL 5MG PO HS glyBURIDE 5MG + METFORMIN HCL 500MG TAB 1 TABLET

PO BID liSINOpril 20MG/HCTZ 12.5MG TAB 1 TABLET PO QD

Risk factors for type 2 DM: family history, HTN, dyslipidemia, smoker, age, HgA1c?

Recommendations for therapy: Assess if the spikes in glucose are post-

prandial, if yes then can add on a meglitinide such as nateglinide (Starlix) 60mg po TID

Or can add on Insulin NPH at bedtime or glargine (Lantus) at bedtime

Can start at 0.1-0.2U/kg IBW and then titrate up

Optimize statin therapy to Zocor 20mg QHS

Monitoring: Renal function: CrCl, serum creatinine Signs of jaundice or hepatic dysfunction Hypoglycemia: finger stick glucose TID Fluid retention, edema Weight gain

References:

1. Hardman Joel, Limbird lee, editors. Goodman&Gilman’s the pharmacological basis of therapeutics. New York: McGraw-hill companies,inc

2. Dipiro J, Talbert R, editors. Pharmacotherapy: A Pathophysiologic Approach. McGraw-Hill Companies, Inc. New York: 2002

3. http://www.clevelandclinic.org/health/health-info/docs/3300/3376.asp?index=11452

4.

5. http://guidelines.gov/summary/summary.aspx?doc_id=7212&nbr=004306&string=diabetes

6. http://www.aocd.org/skin/dermatologic_diseases/acanthosis_nigrica.html7. http://dermatology.cdlib.org/DOJvol6num1/original/acanthosis/katz.html

1. UptoDate. http://uptodateonline.com/application/topic.asp?file=diabetes/25035

2. http://uptodateonline.com/application/topic.asp?file=diabetes/250353. http://guidelines.gov/summary/summary.aspx?

doc_id=7212&nbr=004306&string=diabetes

4. http://online.statref.com/Document.aspx?FxID=27&DocID=344&QueryID=21476&SessionID=5541B0ANAKYVMKCH

5. http://guidelines.gov/algorithm/3306/NGC3306_1.pdf

6. Harrison's Principles of Internal Medicine - 16th Ed. (2005)

7. http://online.statref.com/Document.aspx?DocId=2184&FxId=55&SessionId=54DBF6HNEZUTEQVW&Scroll=1&Index=0

8. Treatment Guidelines from The Medical Letter. Volume 3, Issue 36. August 2005

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