Inhaled Human Insulin Treatment in Patients with Type 2 Diabetes Mellitus

Matthew Faiman

Background

• Conventional Insulin therapy relies on daily injections

• Intensive insulin therapy relies on multiple, frequent insulin injections

BUT…..

• multiple injections are inconvenient

• poorly approximates endogenous insulin secretion

• requires time, effort, communication and commitment

Alternate means of insulin are now underway

• humalog• insulin pumps• inhaled insulin

Inhaled Insulin

• pulmonary delivery includes a powder insulin along with an aerosol delivery system

METHODSInclusion Criteria• patients age 35-65

• 100%- 175% of IBW

• were on stable insulin schedule (2-3 injections)

• HbA1c levels of 7%- 11.9%

• fasting C-peptide concentrations 0.2 pmol/ml or greater

• normal CXR

• normal PFTs

METHODSExclusion Criteria

• serum creatinine > or = to 3.0 mg/dl

• major organ system disease, except HTN and end-organ disease (neuropathy and retinopathy)

• smoking

• insulin pump

• 4 or more injections of insulin

• more than 150 units of insulin daily

• concomitant oral hypoglycemic

STUDY DESIGN

• patients receiving inhaled insulin were given ultra-lente insulin at bedtime

• Inhaled insulin was administered qac

• administered as 1 to 2 inhalations

• pharmacokinetics approximated 1 mg inhaled to be equivalent to 3 units of SC insulin

• dose titrated to glucose response

• ? Single unit adjustments…. eg 0.5 mg inhaled insulin

STUDY DESIGN

• blood glucose measured prior to insulin

• if target range (100-160 mg/dl) exceeded then

adjustment made to hs ultra-lente dose

• Hypoglycemia determined by symptoms and

by BG less than 50-60

Clinical Variables

• PFTs- FEV1, FVC, PEF, lung volumes, DLCO and oximetry

• HbA1c

STASTICAL ANALYSIS

• assessed by 12 week change in HbA1c level from baseline

• 95% Confidence Intervals for mean of the change calculated

• used Standard Error (SE)

• SE = SD/square root of sample size N

• Student’s t-test

• data presented as mean +/- SD

RESULTS

• N= 26 participants

• 16 were men with avg. BMI 30

• 10 women with avg BMI 33

• Avg age 51.1 yrs (39-64)

• Avg duration of diabetes 11.2 yrs (0.9-35)

• Inhaled insulin improved glycemic control

RESULTS

• HbA1c decreased from 8.67% +/- 1.44% baseline to 7.96% +/- 1.37% by 12 weeks

• change was -0.71% +/- 0.72%

• C.I. -1.00% to -0.42%

• 18 patients (69%) experienced mild-mod hypoglycemic episodes. No severe episodes noted

• average of 0.83 episodes per month

RESULTS

• No significant change from baseline in post prandial BG levels (240+/- 56 mg/dl) at baseline vs. 241+/- 57 mg/dl

• no significant weight gain delta -0.3 +/- 2.9kg

• No significant change from baseline spirometry, Lung volumes, DLCO or oximetry