1. Hospitalizations Due to Severe Hypoglycemia in Patients with Type 1 Diabetes Mellitus: US National Perspective
Singh G, Mithal A, Mannalithara A, Sehgal A,
Bron M, Dabbous O, Peng X
ICORE
Stanford University
Takeda Pharmaceuticals

2. Disclosures Supported by a grant from Takeda Pharmaceuticals
Drs. Bron and Peng are employees of Takeda Pharmaceuticals
Dr. Dabbous is a former employee of Takeda Pharmaceuticals

3. Type 1 Diabetes Mellitus in US
Type 1 Diabetes Mellitus (T1DM) affects >1 million Americans
In adults, T1DM constitutes approximately 5% of all diagnosed cases of diabetes
Tight glycemic control using intensive insulin therapy significantly reduces long-term microvascular and macrovascular complications in T1DM (The Diabetes Control and Complications Trial (DCCT))
U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National diabetes fact sheet: national estimates and general information on diabetes and prediabetes in the United States, Available at Accessed August 29,2012.

4. Pathophysiology of Hypoglycemia
Hyper-insulinemia
Compromised response to falling glucose level
Hypoglycemia

5. Objective
To examine the prevalence and costs and payer status of severe hypoglycemia hospitalizations in T1DM patients in the US

6. Methods and Data Nationwide Inpatient Sample (NIS)
Largest publicly available all-payer inpatient care database
20% stratified sample of all U.S. hospitalizations (1988 – 2011)
~5 to 8 million records of inpatient stays per year from about 1,000 hospitals representing ~85 – 96 % of all non–federal hospitals
Complex survey design with multistage strata and clustering
Strict quality-control and extensive validation

7. 2009 NIS: Represents 96% of US Population
Year
Data Sources
Number of
Hospitals
Number of
Discharges
in the NIS,
Unweighted
Weighted for
National
Estimates
2009
AR AZ CA CO CT FL GA HI IL IN IA
KS LA KY MD MA ME MI MN MO MT NC NE
NH NJ NM NY NV OH OK OR PA RI SC SD
TN TX UT VA VT WA WI WV WY
(Added NM and MT)
1,050
7,810,762
39,434,956
NIS 2009

8. NIS: Data Characteristics
Over 100 clinical and non-clinical variables for each hospital stay, for example:
Primary and secondary diagnoses
Primary and secondary procedures.
Admission and discharge status
Patient demographics (e.g., gender, age, race, median income for ZIP Code).
Expected payment source
Length of stay and total charges
Hospital characteristics (e.g., ownership, size, teaching status)

9. Calculating National Estimates
The NIS is drawn from those states participating in Healthcare Cost and Utilization Project (HCUP)
These states comprised over 96% of the US population in 2009
Weights are provided to calculate national estimates

10. NIS Sample Weights (Details)
Sample weights calculated as ratio of discharges in community hospitals to discharges in the sample
Sample weights constant for all discharges within each stratum, with the exception of adjustments for hospitals with missing quarters of data.
Number of discharges in the universe calculated from total number of discharges reported in the American Hospital Association (AHA) hospital survey data
Sum of the sample weights in each stratum represents total number of discharges reported in the AHA survey

11. Study Cohort
All inpatient hospitalizations in 2009 with primary or secondary diagnosis of:
T1DM (ICD9 codes 250.x1, 250.x3), and
Hypoglycemia (ICD9 codes 250.8x, 251.0x, 251.1x, 251.2x) in patients aged ≥18 years.
Denominator: US resident population (over 18 years): 232,637,3621
1 Estimated from US Census Bureau Data, 2010 census

12. Statistics
SAS ( Statistical Analysis System) version 9.3 procedure PROC SURVEYMEANS used for calculating sample statistics and appropriate variances based on data from complex sampling designs
All estimates reported with 95% Confidence Intervals (CI)

13. Results

14. Total All-Cause US Hospitalizations (18 years or older, 2009)
33.1 million in million person-years
14,226 per 100,000 person-years
T1DM
326,395 All-Cause Hospitalizations (1%)
140 per 100,000 US population
Hypoglycemia in T1DM
20,839 hospitalizations (9 per 100,000 US pop)
6.4% of all T1DM hospitalizations

15. Total All-Cause US Hospitalizations (18 years or older, 2009)
33.1 million in million person-years
14,226 per 100,000 person-years
T2DM
7.2 million All-Cause Hospitalizations (21.7%)
3,100 per 100,000 US population
Hypoglycemia in T2DM
248,422 hospitalizations (107 per 100,000)
3.4% of all T1DM hospitalizations

16. Prevalence (US, 2009) (18 years of older)
All-cause hospitalizations:
14,226 per 100,000 person years
T1DM hospitalizations:
1 % of all-cause hospitalizations
140 per 100,000 US population
Hypoglycemia in T1DM hospitalizations:
6.38% of all T1DM hospitalizations (95%CI= )
9 per 100,000 US population

17. T2DM Hospitalizations1
T2DM Hospitalizations in 18 years and older in 2009 :
7.2 million hospitalizations
21.7% of all-cause hospitalizations
3,100 per 100,000 US population
Hypoglycemia in T2DM Hospitalizations:
248,422 hospitalizations with Hypoglycemia in T2DM
3.44% of all T2DM hospitalizations (CI = )
107 per 100,000 US population
1 Data Previously Presented at EASD, 2012:Hospitalizations due to severe hypoglycemia in patients with type 2 diabetes: a US national perspective – Singh, G. et.al. EASD, 3-7th Nov, 2012, Berlin, Germany.

18. Hypoglycemia Hospitalizations as % of All-Cause T1DM and T2DM Hospitalizations

19. Hypoglycemia Hospitalizations as a % of All-Cause T1DM hospitalizations by Gender
CI female 5.9% to 6.1%
CI male 6.7% - 7%

20. Mean Age at Admission with Diagnosis of Hypoglycemia with T1DM

21. Hospitalization Type in T1DM Hypoglycemia Most Hospitalizations are Non-Elective

22. Length of Stay T1DM patients with hypoglycemia stayed longer compared to those with all-cause hospitalizations

23. Charges for Hospitalizations with Hypoglycemia in T1DM (US$ per admission)

24. National Bill : Total Charges for Hypoglycemia Hospitalizations in T1DM
Total hospitalizations = 20,839 (95% CI = 19, ,445)
Charge per hospitalization = $46,039 (CI = $42,144-$49,934)
Total charges = $ 959,406,721
As a comparison, hypoglycemia hospitalizations in T2DM :
Total hospitalizations = 248,422 (CI = 234, ,523)
Charges per hospitalization = $48,569 (CI = $45,781-$51,357)
Total charges = $ billion
Average Charge of US All-Cause Hospitalization: $33,232

25. Who is paying for T1DM Hypoglycemia Hospitalizations
Who is paying for T1DM Hypoglycemia Hospitalizations ? Medicare and Medicaid are responsible for 64% of Payment

26. Inpatient Case Fatality Rate in T1DM Hypoglycemia Hospitalizations
Case-fatality in T1DM Hypoglycemia
284 deaths
Case-fatality = 1.36% (CI = %)
Case Fatality rate for all-cause T1DM hospitalizations
1.4% (CI = %)
Case Fatality rate for all-cause hospitalizations
2.2%

27. Limitations and Strengths
No unique patient identifiers.
Dependence on ICD9 codes.
No information on lifestyle factors or medications.
Charges vs. Costs
Study limited to adults 18 years or older
Nationwide sample of over 96% of all US population – robust data.
Stratified, randomized sample from US hospitals - not a “convenience” sample.

28. Can we predict hypoglycemia?
Future Work
Can we predict hypoglycemia?

29. Conclusions
Hypoglycemia in T1DM was associated with 20,839 hospitalizations and 284 deaths in 2009, and a total cost of about $1 billion, most of which is paid by Medicare and Medicaid.
While aggressive glycemic control remains important for patients, the significant clinical and financial implications of severe hypoglycemia should also be noted.
Careful selection of anti-diabetic drugs and close monitoring should be considered to reduce the risk of severe hypoglycemia.
Development of novel anti-diabetics to reduce hypoglycemia while maintaining glycemic control would be highly desirable.