Severe Hypoglycemia and Diabetic Ketoacidosis in Adults With Type 1 Diabetes

8/10/2019 Severe Hypoglycemia and Diabetic Ketoacidosis in Adults With Type 1 Diabetes

1/8

Severe Hypoglycemia and Diabetic Ketoacidosis in Adults WithType 1 Diabetes: Results From the T1D Exchange Clinic Registry

Ruth S. Weinstock,Dongyuan Xing,David M. Maahs,Aaron Michels,Michael R.

Rickels,Anne L. Peters,Richard M. Bergenstal,Breanne Harris,Stephanie N.DuBose,Kellee M. Miller,Roy W. Beck,andfor the T1D Exchange Clinic Network

DOI:http://dx.doi.org/10.1210/jc.2013-1589 Received: March 07, 2013Accepted: June 04, 2013Published Online: June 12, 2013

Abstract

Context:

Few studies have assessed factors associated with severe hypoglycemia (SH) and diabetic ketoacidosis

(DKA) in adults with type 1 diabetes (T1D).

Objective:

Our objective was to determine frequency of and factors associated with the occurrence of SH and DKA

in adults with T1D.

Design and Setting:

We conducted a cross-sectional analysis from the T1D Exchange clinic registry at 70 U.S. endocrinology

centers.

Patients:

Analysis included 7012 participants in the T1D Exchange clinic registry aged 26 to 93 years old with T1D

for 2 years.

Results:

Higher frequencies of SH and DKA were associated with lower socioeconomic status (P< .001). SH was

strongly associated with diabetes duration (P< .001), with 18.6% of those with diabetes 40 years having

an event in the past 12 months. SH frequency was lowest in those with hemoglobin A1c (HbA1c) levels of

7.0% (53 mmol/mol) to 7.5% (58 mmol/mol), being higher in those with HbA1c levels 58 mmol/mol). DKA frequency increased with higher HbA1c levels (P< .001), with

21.0% of those with HbA1c 10.0% (86 mmol/mol) having an event in the past 12 months.

Conclusions:

SH and DKA are more common in those with lower socioeconomic status. DKA, most common in those

with HbA1c 10.0% (86 mmol/mol), should be largely preventable. In contrast, SH, most frequent withdiabetes 40 years duration, cannot be abolished given the limitation of current therapies. To reduce SH

in adults with longstanding diabetes, consideration should be given to modifying HbA1c goals, particularly

in patients with very low HbA1c levels.

Severe hypoglycemia (SH) and diabetic ketoacidosis (DKA) are major acute complications of type

1 diabetes (T1D). Many studies are available concerning the prevalence of these complications in

children and adolescents with T1D, but there is a paucity of data in adults. Although recent data are

available from European registries (1, 2), recent U.S. data are largely from clinical trials, which may not be

representative (3, 4). To provide current data in clinical practice settings in the United States, we used the
http://press.endocrine.org/action/doSearch?text1=Weinstock%2C+R+S&field1=Contribhttp://press.endocrine.org/action/doSearch?text1=Weinstock%2C+R+S&field1=Contribhttp://press.endocrine.org/action/doSearch?text1=Xing%2C+D&field1=Contribhttp://press.endocrine.org/action/doSearch?text1=Xing%2C+D&field1=Contribhttp://press.endocrine.org/action/doSearch?text1=Xing%2C+D&field1=Contribhttp://press.endocrine.org/action/doSearch?text1=Maahs%2C+D+M&field1=Contribhttp://press.endocrine.org/action/doSearch?text1=Maahs%2C+D+M&field1=Contribhttp://press.endocrine.org/action/doSearch?text1=Maahs%2C+D+M&field1=Contribhttp://press.endocrine.org/action/doSearch?text1=Michels%2C+A&field1=Contribhttp://press.endocrine.org/action/doSearch?text1=Michels%2C+A&field1=Contribhttp://press.endocrine.org/action/doSearch?text1=Michels%2C+A&field1=Contribhttp://press.endocrine.org/action/doSearch?text1=Rickels%2C+M+R&field1=Contribhttp://press.endocrine.org/action/doSearch?text1=Rickels%2C+M+R&field1=Contribhttp://press.endocrine.org/action/doSearch?text1=Rickels%2C+M+R&field1=Contribhttp://press.endocrine.org/action/doSearch?text1=Rickels%2C+M+R&field1=Contribhttp://press.endocrine.org/action/doSearch?text1=Peters%2C+A+L&field1=Contribhttp://press.endocrine.org/action/doSearch?text1=Peters%2C+A+L&field1=Contribhttp://press.endocrine.org/action/doSearch?text1=Peters%2C+A+L&field1=Contribhttp://press.endocrine.org/action/doSearch?text1=Bergenstal%2C+R+M&field1=Contribhttp://press.endocrine.org/action/doSearch?text1=Bergenstal%2C+R+M&field1=Contribhttp://press.endocrine.org/action/doSearch?text1=Bergenstal%2C+R+M&field1=Contribhttp://press.endocrine.org/action/doSearch?text1=Harris%2C+B&field1=Contribhttp://press.endocrine.org/action/doSearch?text1=Harris%2C+B&field1=Contribhttp://press.endocrine.org/action/doSearch?text1=Harris%2C+B&field1=Contribhttp://press.endocrine.org/action/doSearch?text1=DuBose%2C+S+N&field1=Contribhttp://press.endocrine.org/action/doSearch?text1=DuBose%2C+S+N&field1=Contribhttp://press.endocrine.org/action/doSearch?text1=DuBose%2C+S+N&field1=Contribhttp://press.endocrine.org/action/doSearch?text1=DuBose%2C+S+N&field1=Contribhttp://press.endocrine.org/action/doSearch?text1=Miller%2C+K+M&field1=Contribhttp://press.endocrine.org/action/doSearch?text1=Miller%2C+K+M&field1=Contribhttp://press.endocrine.org/action/doSearch?text1=Miller%2C+K+M&field1=Contribhttp://press.endocrine.org/action/doSearch?text1=Beck%2C+R+W&field1=Contribhttp://press.endocrine.org/action/doSearch?text1=Beck%2C+R+W&field1=Contribhttp://press.endocrine.org/action/doSearch?text1=Beck%2C+R+W&field1=Contribhttp://press.endocrine.org/action/doSearch?ContribStored=For+The+TD+Exchange+Clinic+Networkhttp://press.endocrine.org/action/doSearch?ContribStored=For+The+TD+Exchange+Clinic+Networkhttp://press.endocrine.org/action/doSearch?ContribStored=For+The+TD+Exchange+Clinic+Networkhttp://dx.doi.org/10.1210/jc.2013-1589http://dx.doi.org/10.1210/jc.2013-1589http://dx.doi.org/10.1210/jc.2013-1589http://dx.doi.org/10.1210/jc.2013-1589http://press.endocrine.org/action/doSearch?ContribStored=For+The+TD+Exchange+Clinic+Networkhttp://press.endocrine.org/action/doSearch?text1=Beck%2C+R+W&field1=Contribhttp://press.endocrine.org/action/doSearch?text1=Miller%2C+K+M&field1=Contribhttp://press.endocrine.org/action/doSearch?text1=DuBose%2C+S+N&field1=Contribhttp://press.endocrine.org/action/doSearch?text1=DuBose%2C+S+N&field1=Contribhttp://press.endocrine.org/action/doSearch?text1=Harris%2C+B&field1=Contribhttp://press.endocrine.org/action/doSearch?text1=Bergenstal%2C+R+M&field1=Contribhttp://press.endocrine.org/action/doSearch?text1=Peters%2C+A+L&field1=Contribhttp://press.endocrine.org/action/doSearch?text1=Rickels%2C+M+R&field1=Contribhttp://press.endocrine.org/action/doSearch?text1=Rickels%2C+M+R&field1=Contribhttp://press.endocrine.org/action/doSearch?text1=Michels%2C+A&field1=Contribhttp://press.endocrine.org/action/doSearch?text1=Maahs%2C+D+M&field1=Contribhttp://press.endocrine.org/action/doSearch?text1=Xing%2C+D&field1=Contribhttp://press.endocrine.org/action/doSearch?text1=Weinstock%2C+R+S&field1=Contrib


2/8

large database of the T1D Exchange clinic registry to assess the frequencies of and identify factors

associated with SH and DKA in adults with T1D. We hypothesized that rates of DKA would be positively

associated with hemoglobin A1c (HbA1c) and that SH would be inversely associated with HbA1c.

Moreover, we hypothesized that rates of DKA and SH would be associated with factors such as

socioeconomic status, age, pump use, and diabetes duration.

Subject and methods

The T1D Exchange Clinic Network includes 70 U.S.-based pediatric and adult endocrinology practices. A

registry of individuals with T1D commenced enrollment in September 2010 (5). Each clinic received

approval from an institutional review board, and informed consent was obtained according to institutional

review board requirements. Data were collected for the registry's central database from the

participant's medical record and by having the participant complete a comprehensive questionnaire, as

previously described (5). This report includes data on 7012 participants enrolled at 44 of the sites through

August 1, 2012, who were at least 26 years old and had duration of T1D of at least 2 years.

Information on the occurrence of SH and DKA in the previous 12 months was obtained from the

participant. Initially, SH was defined as an episode in which the assistance of another individual was

needed or glucagon was given. However, it became apparent that the interpretation of needingassistance varied, and in some cases, glucagon was being given for mild hypoglycemia to avoid SH. As

a result, the questionnaire was modified to change the participant-reported SH definition to be an episode

in which hypoglycemia resulted in seizure or loss of consciousness (LOC); glucose data confirming an

event were not collected. Participant-reported DKA was defined as the occurrence of ketoacidosis that

resulted in overnight hospitalization. SH data were analyzed for the 4973 participants (71%) who

completed the modified questionnaire with the seizure/LOC definition, whereas DKA data were available

for 6796 participants (97%). In addition to participant reporting, information on the occurrence of DKA and

SH also was collected from the clinics' medical records. Clinic-documented DKA was defined as having

hyperglycemia and meeting all of the following criteria: 1) symptoms such as polyuria, polydipsia, nausea,

or vomiting; 2) serum ketones or large/moderate urine ketones; 3) arterial blood pH


3/8

Results

The cohort included 7012 participants 26 to 93 years old; 54% were female, and 91% were non-Hispanic

white. Mean HbA1c (SD) was 7.7% (61 mmol/mol) 1.2% (13.1 mmol/mol). Median diabetes duration

was 24 years (interquartile range 15 to 34 years). Characteristics were similar in the cohort with available

DKA data (n = 6797) and those with available SH data (n = 4973) (Supplemental Table 1, published on

The Endocrine Society's Journals Online web site athttp://jcem.endojournals.org).Severe hypoglycemia

One or more SH events (seizure or LOC) within 12 months was reported by 11.8% of the 4973

participants with available data. SH frequency increased with longer diabetes duration, with the 12-month

frequency of 1 or more events being 18.6% in the 758 participants with diabetesfor 40 years (Figure 1A

andTable 1). Although the frequency of SH increased with older age (P< .001), as can be seen inFigure

1A, the age effect was largely explained by diabetesduration, and in the multivariate model, age was not

a significant factor (Table 1). With respect to HbA1c levels, SH frequency was lowest with HbA1c levels

7.0% (53 mmol/mol) to 7.5% (58 mmol/mol), with frequency being higher at levels above or below this

range (Figure 2A andTable 1). No evidence of a difference in SH frequency was found between adults

with HbA1c levels of 8.0% to 9.0%, 9.0% to 10.0%, and >10.0% (P> .05). There was a trend (P= .01) for

individuals with low (


4/8

Figure 2.A, The 12-month frequency of severe hypoglycemia according to HbA1c level. * Mean HbA1c

averaged over 12 months before enrollment.Pvalue obtained by categorizing HbA1c with 3 levels:


5/8

(tabel 2 ditaronya di bagian ini..)

Participant-reported versus clinic-reported events

The frequency of at least 1 DKA or SH event in the past 12 months was lower from clinic-reported data

from medical record review compared with participant-reported data (3.6% versus 11.8% for SH and 3.2%versus 4.8% for DKA). Logistic models using clinic-reported SH and DKA events to assess associated

factors produced results similar to the models using participant-reported events (Supplemental Tables 2

and 3).

Discussion

Using the T1D Exchange clinic registry data, we determined the frequencies of SH and DKA over the past

12 months in adults with T1D who were being treated at endocrinology practices in the United States.

Compared with the pediatric and young adult cohort in the T1D Exchange clinic registry, the 12-month

frequency of hypoglycemia-induced seizure/LOC in adults was higher (11.8% versus 6.1%) and DKA

frequency was lower (4.8% versus 9.6%) (5). Higher frequencies of both SH and DKA were associatedwith lower socioeconomic status, consistent with previous reports (610).

Our 12-month frequency of at least 1 SH episode with seizure/LOC (11.8%) is substantially higher than

the 2.2% 6-month frequency reported for control group participants with comparable characteristics in the

Juvenile Diabetes Research Foundation Continuous Glucose Monitoring (JDRF CGM) randomized

clinical trial (4)and the 4.8% 12-month frequency in the Sensor-Augmented Pump Therapy for A1c

Reduction (STAR3) trial (3)(R. Bergenstal, MD, personal communication, November 2012). This

suggests that clinical trial data may not be an appropriate source for estimating the real-world frequency

of SH. Most other registry and observational studies have reported SH frequency based on a definition of

an event in which the assistance of another person was needed. If it is assumed that about one-third of

SH events using this definition involved seizure/LOC, then the data on the 12-month SH frequency are

similar to our SH frequency: 31.5% in the Eurodiab Prospective Complications Study (2), 36.7% in a

Danish-English survey (7), 40.5% in a Dutch study (11), and 27% in a Swedish survey (12). The UKHypoglycemia Study Group reported an SH frequency of 22% over a 12-month period in adults with T1D

for 15 years (13). It is difficult to compare our SH frequency

with that of certain other studies such as the Diabetes Control and Complications Trial (DCCT) due to

differences in populations, SH definition, and reporting metrics (eg, frequency of 1 or more events versus

rate per 100 000 person-years).

Individuals with longstanding diabetes were at greatest risk for SH irrespective of age, with almost 1 in 5

of those with duration of 40 or more years reporting hypoglycemia-induced seizure/LOC within the

previous 12 months. Based on the work of Cryer (14)and others, it is likely that the increased risk with

longer duration is related to the loss of endogenous insulin secretion (C-peptide negative) removing any

autoregulatory capability to reduce excessive insulin, a greater prevalence of defective glucose

counterregulation with hypoglycemic unawareness including a reduced plasma glucagon response to

hypoglycemia, and loss of the epinephrine response to hypoglycemia (hypoglycemia-associated

autonomic failure). Impairments related to chronic diabetes-related complications and other comorbidities

also could be contributing factors. We did not find an association between SH and gender in contrast with

the JDRF CGM randomized trial and the Diabetes Control and Complications Trial (DCCT), which found a

higher SH rate in females (15).

The lowest SH frequency was seen in those with HbA1c levels in the range of 7.0% (53 mmol/mol) to

7.5% (58 mmol/mol), with the frequency being higher in those with HbA1c levels 58 mmol/mol). These data support the contention that hypoglycemia is an important barrier

for the achievement of near-normal glycemic control in T1D. There was a suggestion in the data that SH

frequency might be higher in those who are the most insulin sensitive (based upon lower insulin


6/8

requirements), but there was not an association between SH and BMI. This suggests that the ability to

achieve glycemic targets varies in people with T1D. This may be related to differences in C-peptide

status, insulin sensitivity (independent of obesity), and/or varying capacities to secrete glucagon and

other factors. These data suggest that the avoidance of SH requires setting individualized flexible

glycemic targets, with caution in recommending a goal HbA1c of


7/8

longstanding diabetes, given the limitation of current therapies, consideration should be given to

modifying HbA1c goals, particularly in patients with very low HbA1c levels and SH. In addition to

hypoglycemic risk, the decision to raise the target HbA1c should take into consideration age, self-care

capacities, presence of comorbidities including vascular complications, and life expectancy.

Abbreviations:BMI body mass index

DKA diabetic ketoacidosis

HbA1c hemoglobin A1c

JDRF CGM Juvenile Diabetes Research Foundation Continuous Glucose Monitoring

LOC loss of consciousness

SH severe hypoglycemia

T1D type 1 diabetes.

Acknowledgments

We acknowledge the patients who chose to participate in this registry and the T1D Exchange Clinic

Network investigators and coordinators for their hard work and dedication. A listing of clinical sites,investigators, and coordinators participating in the clinic registry is located in the Supplemental Appendix.

The T1D Exchange Clinic Network is funded through a grant provided by the Leona M. and Harry B.

Helmsley Charitable Trust. The Helmsley Trust had no role in the study design; collection, analysis, and

interpretation of data; writing of this report; or the decision to submit the report for publication.

R.S.W. initiated the idea for the manuscript, researched data, contributed to discussion, wrote the

manuscript, and reviewed/edited the manuscript. D.X. researched data, contributed to discussion, and

wrote the manuscript. A.M. contributed to discussion and reviewed/edited the manuscript. M.R.

contributed to discussion and reviewed/edited the manuscript. A.P. contributed to discussion and

reviewed/edited the manuscript. R.M.B. contributed to discussion and reviewed/edited the manuscript.

B.H. contributed to discussion and reviewed/edited the manuscript. S.D. researched data, contributed to

discussion, and wrote the manuscript. K.M. researched data, contributed to discussion, and

reviewed/edited the manuscript. R.W.B. contributed to discussion and reviewed/edited the manuscript.R.W.B. is the guarantor of this work and, as such, had full access to all the data in the study and takes

responsibility for the integrity of the data and accuracy of the data analysis.

Disclosure Summary: D.X., B.H., S.D., and K.M. have no disclosures. R.S.W.'s nonprofit employer has

received grant money as the site for multicenter clinical trials sponsored by Eli Lilly, Medtronic, Astra-

Zeneca, GlaxoSmithKline, and Johnson & Johnson. D.M.'s nonprofit employer has received research

grants from Eli Lilly, Abbott, and Diabetes Care. A.M.'s nonprofit employer has received a research grant

from Novartis. M.R. has received consultancy fees from Longevity Biotech. A.P.'s nonprofit employer has

received research grants from Sanofi; consultancy fees from Eli Lilly, Roche, Janssen, Amylim, and

Sanofi; and payment for lectures from Amylin, Abbott, Eli Lilly, NovoNordisk, Takeda, and Dexcom.

R.M.B. has served on a scientific advisory board, consulted or performed clinical research with

Abbott Diabetes Care, Amylin, Bayer, Becton Dickinson, Boehringer Ingelheim, Intuity, Calibra, DexCom,

Eli Lilly, Halozyme, Helmsley Trust, Hygieia, Johnson & Johnson, Medtronic, Merck, National Institutes ofHealth, Novo Nordisk, ResMed, Roche, Sanofi, and Takeda. His employer, Park Nicollet, has contracts

with the listed companies for his services, and no personal income goes to R.M.B. He has inherited Merck

stock and has been a volunteer officer of the American Diabetes Association. R.W.B.'s nonprofit employer

has received consultant payments on his behalf from Sanofi and Animas and a research grant from

NovoNordisk with no personal compensation to R.W.B.


8/8

References

1. M Gimnez, Lpez JJ, Castell C, Conget I. Hypoglycaemia and cardiovascular disease in type

1 diabetes. Results from the Catalan National Public Health registry on insulin pump

therapy. Diabetes Res Clin Pract. 2012;96:e23e25.[CrossRef][Medline]

2. Gruden G, Barutta F, Chaturvedi N, . Severe hypoglycemia and cardiovascular disease incidence in

type 1 diabetes: the EURODIAB Prospective Complications Study. DiabetesCare. 2012;35:15981604.[CrossRef][Medline]

3. Bergenstal RM, Tamborlane WV, Ahmann A, . 2010 Effectiveness of sensor-augmented insulin-pump

therapy in type 1 diabetes. N Engl J Med. 2010;363:311320.[CrossRef][Medline]

4. Juvenile Diabetes Research Foundation Continuous Glucose Monitoring Study

Group;Tamborlane WV, Beck RW, Bode BW, . Continuous glucose monitoring and intensive treatment of

type 1 diabetes. N Engl J Med 2008;359:14641476.[CrossRef][Medline]

5. Beck RW, Tamborlane WV, Bergenstal RM, Miller KM, Dubose SN, Hall CA; T1D Exchange Clinic

Network. The T1D Exchange Clinic Registry. J Clin Endocrinol Metab.2012;97:4383

4389.[Abstract][Medline]

6. Mhlhauser I, Overmann H, Bender R, Bott U, Berger M. Risk factors of severe hypoglycaemia in adult

patients with type I diabetes: a prospective population based study. Diabetologia. 1998;41:1274

1282.[CrossRef][Medline]7. Musey VC, Lee JK, Crawford R, Klatka MA, McAdams D, Phillips LS. Diabetes in urban African-

Americans. I. Cessation of insulin therapy is the major precipitating cause

of diabeticketoacidosis. Diabetes Care. 1995;18:483489.[CrossRef][Medline]

8. Pedersen-Bjergaard U, Pramming S, Heller SR, . Severe hypoglycaemia in 1076 adult patients with

type 1 diabetes: influence of risk markers and selection. Diabetes Metab Res Rev. 2004;20:479

486.[CrossRef][Medline]

9. Randall L, Begovic J, Hudson M, . Recurrent diabetic ketoacidosis in inner-city minority patients:

behavioral, socioeconomic, and psychosocial factors. Diabetes Care.2011;34:1891


10. Umpierrez GE, Kelly JP, Navarrete JE, Casals MM, Kitabchi AE. Hyperglycemic crises in urban

blacks. Arch Intern Med. 1997;157:669675.[CrossRef][Medline]

11. ter Braak EW, Appelman AM, van de Laak M, Stolk RP, van Haeften TW, Erkelens DW.Clinicalcharacteristics of type 1 diabetic patients with and without severe

hypoglycemia.Diabetes Care. 2000;23:14671471.[CrossRef][Medline]

12. Bragd J, Adamson U, Lins PE, Wredling R, Oskarsson P. A repeated cross-sectional survey of severe

hypoglycaemia in 178 type 1 diabetes mellitus patients performed in 1984 and

1998. Diabet Med. 2003;20:216219.[CrossRef][Medline]

13. UK Hypoglycaemia Study Group. Risk of hypoglycaemia in types 1 and 2 diabetes: effects of

treatment modalities and their duration. Diabetologia. 2007;50:11401147.[CrossRef][Medline]

14. Cryer PE. Hypoglycemia in type 1 diabetes mellitus. Endocrinol Metab Clin North Am.2010;39:641


15. Juvenile Diabetes Research Foundation Continuous Glucose Monitoring Study Group;Fiallo-

Scharer R, Cheng J, Beck RW, . Factors predictive of severe hypoglycemia in type 1diabetes: analysis

from the Juvenile Diabetes Research Foundation continuous glucose monitoring randomized control trial

dataset. Diabetes Care. 2011;34:586590.[CrossRef][Medline]

16. Hirai FE, Moss SE, Klein BE, Klein R. Severe hypoglycemia and smoking in a long-term type

1 diabetic population: Wisconsin Epidemiologic Study

of Diabetic Retinopathy.Diabetes Care. 2007;30:14371441.[CrossRef][Medline]

17. Stephenson J, Fuller JH. Microvascular and acute complications in IDDM patients: the EURODIAB

IDDM Complications Study. Diabetologia. 1994;37:278285.[CrossRef][Medline]
http://popreflink%288%2C%27b1%27%2C%2722306058%27%29/http://popreflink%288%2C%27b1%27%2C%2722306058%27%29/http://popreflink%288%2C%27b1%27%2C%2722306058%27%29/http://popreflink%288%2C%27b2%27%2C%2722584135%27%29/http://popreflink%288%2C%27b2%27%2C%2722584135%27%29/http://popreflink%288%2C%27b2%27%2C%2722584135%27%29/http://popreflink%288%2C%27b4%27%2C%2718779236%27%29/http://popreflink%288%2C%27b4%27%2C%2718779236%27%29/http://popreflink%288%2C%27b4%27%2C%2718779236%27%29/http://newwindow%28%27http//dx.doi.org/10.1210%2Fjc.2012-1561')http://newwindow%28%27http//dx.doi.org/10.1210%2Fjc.2012-1561')http://popreflink%288%2C%27b5%27%2C%2722996145%27%29/http://popreflink%288%2C%27b5%27%2C%2722996145%27%29/http://popreflink%288%2C%27b5%27%2C%2722996145%27%29/http://popreflink%288%2C%27b6%27%2C%279833933%27%29/http://popreflink%288%2C%27b6%27%2C%279833933%27%29/http://popreflink%288%2C%27b6%27%2C%279833933%27%29/http://popreflink%288%2C%27b7%27%2C%277497857%27%29/http://popreflink%288%2C%27b7%27%2C%277497857%27%29/http://popreflink%288%2C%27b7%27%2C%277497857%27%29/http://popreflink%288%2C%27b8%27%2C%2715386817%27%29/http://popreflink%288%2C%27b8%27%2C%2715386817%27%29/http://popreflink%288%2C%27b8%27%2C%2715386817%27%29/http://popreflink%288%2C%27b9%27%2C%2721775761%27%29/http://popreflink%288%2C%27b9%27%2C%2721775761%27%29/http://popreflink%288%2C%27b9%27%2C%2721775761%27%29/http://popreflink%288%2C%27b10%27%2C%279080921%27%29/http://popreflink%288%2C%27b10%27%2C%279080921%27%29/http://popreflink%288%2C%27b10%27%2C%279080921%27%29/http://popreflink%288%2C%27b11%27%2C%2711023138%27%29/http://popreflink%288%2C%27b11%27%2C%2711023138%27%29/http://popreflink%288%2C%27b11%27%2C%2711023138%27%29/http://popreflink%288%2C%27b12%27%2C%2712675666%27%29/http://popreflink%288%2C%27b12%27%2C%2712675666%27%29/http://popreflink%288%2C%27b12%27%2C%2712675666%27%29/http://popreflink%288%2C%27b13%27%2C%2717415551%27%29/http://popreflink%288%2C%27b13%27%2C%2717415551%27%29/http://popreflink%288%2C%27b13%27%2C%2717415551%27%29/http://popreflink%288%2C%27b14%27%2C%2720723825%27%29/http://popreflink%288%2C%27b14%27%2C%2720723825%27%29/http://popreflink%288%2C%27b14%27%2C%2720723825%27%29/http://popreflink%288%2C%27b16%27%2C%2717372156%27%29/http://popreflink%288%2C%27b16%27%2C%2717372156%27%29/http://popreflink%288%2C%27b16%27%2C%2717372156%27%29/http://popreflink%288%2C%27b17%27%2C%278174842%27%29/http://popreflink%288%2C%27b17%27%2C%278174842%27%29/http://popreflink%288%2C%27b17%27%2C%278174842%27%29/http://popreflink%288%2C%27b17%27%2C%278174842%27%29/http://popreflink%288%2C%27b16%27%2C%2717372156%27%29/http://popreflink%288%2C%27b14%27%2C%2720723825%27%29/http://popreflink%288%2C%27b13%27%2C%2717415551%27%29/http://popreflink%288%2C%27b12%27%2C%2712675666%27%29/http://popreflink%288%2C%27b11%27%2C%2711023138%27%29/http://popreflink%288%2C%27b10%27%2C%279080921%27%29/http://popreflink%288%2C%27b9%27%2C%2721775761%27%29/http://popreflink%288%2C%27b8%27%2C%2715386817%27%29/http://popreflink%288%2C%27b7%27%2C%277497857%27%29/http://popreflink%288%2C%27b6%27%2C%279833933%27%29/http://popreflink%288%2C%27b5%27%2C%2722996145%27%29/http://newwindow%28%27http//dx.doi.org/10.1210%2Fjc.2012-1561')http://popreflink%288%2C%27b4%27%2C%2718779236%27%29/http://popreflink%288%2C%27b2%27%2C%2722584135%27%29/http://popreflink%288%2C%27b1%27%2C%2722306058%27%29/

Documents

Severe Hypoglycemia and Diabetic Ketoacidosis in Adults With Type 1 Diabetes