Up and Up:
Significant Insulin Dosing for a Type B Insulin Resistant Diabetic in DKA
Wendy Gu, MD; Pamela Prescott, MD, MHS, MPH
University of California, Davis Medical Center; Sacramento, CA
Learning objectives
Clinical course
• Diabetic ketoacidosis is an acute complication in diabetic
patients precipitated by infection, inflammation, ischemia, or
an iatrogenic cause.
• Admitted to the ICU and started on an
insulin drip and IV fluids.
• DKA requires treatment with intravenous insulin, aggressive
fluid repletion, and electrolyte replacement.
• Type B insulin resistant diabetes is an autoimmune disease,
usually occurring with a concomitant rheumatologic disease.
• Patients with Type B insulin resistant diabetes in DKA may
require significantly increased amounts of insulin over
several days before anion gap closure and resolution of
ketonemia.
Case presentation
• 23 year old African American female with Type B insulin
resistant diabetes and SLE presented to the ED with
complaints of fatigue, decreased oral intake, and shortness
of breath.
• Found to have an anion gap metabolic acidosis, ketonuria,
ketonemia, and hyperglycemia consistent with DKA.
• HD 2: insulin drip rate over 200 units/hr
2500
• HD 4: developed steroid-induced acne and
started on broad spectrum IV antibiotics for
an axillary abscess. Insulin drip rate was
over 500 units/hr, and although her anion
gap had closed, ketonemia persisted.
2000
1500
• HD8: maximum insulin drip rate of 1225
units/hr
1000
• HD 9: ketonemia resolved
ANA
Anti-smith Ab
Anti-U1RNP Ab
Insulin antibody
IVF (ml)
500
• HD 11: pharmacy procured U500 insulin for
subcutaneous administration. Transferred
to the general ward.
• Home insulin regimen: 1500 units of concentrated U500
regular insulin TIDAC + additional sliding scale.
• Had received cycle 4/4 of treatment with rituximab and
methylprednisolone two days prior to presentation.
3000
Insulin dose (units/hr)
0
7/1
1:640
>5.0
>240.0
7.0
1Jul
Glucose
2Jul
7/2
Glucose
7/3
3Jul
7/4
7/5
4Jul
7/6
7/7
5Jul
7/8
7/9
6Jul
7Jul
8Jul
9Jul
262 306 266 282 378 253 289 205 254 326 348 276 204 284 212 285 253 241 268 283 180 210 229 206 144 273
Insulin dose (units/hr) 8.5
28
60 104 214 295 405 485 545 525 645 705 795 865 905 925 985 10051135 1175 1150 12151225 1145 1085 0
IVF (ml)
132 346 616 11691995 2371 3920 41572937 914 10881170 1318 14362010 2751 18771603 2995 3595 20032063 1791 14441396
Discussion
• Type B insulin resistant diabetes is an exceedingly rare diagnosis occurring in the presence of a concomitant rheumatologic
disease, most notably lupus, Sjogren’s, or mixed connective tissue disease.
• This patient was felt to have developed insulin resistance in the setting SLE; Type B insulin resistant diabetes was diagnosed with
elevated levels of IR autoantibodies and negative glutamic acid decarboxylase antibodies.
• For Type B insulin resistant diabetics, the amount of insulin needed on a daily basis—and while in DKA—may be vastly increased
due to the presence of insulin receptor (IR) autoantibodies, which must be out-competed by the insulin.
• She underwent immunosuppression with four cycles of rituximab and methylprednisolone, which was thought to have triggered this
episode of DKA. She was recently started on azathioprine in attempt to suppress her IR autoantibodies.
References
Arioglu, et al. “Clinical Course of the Syndrome of Autoantibodies to the Insulin Receptor (Type B Insulin Resistance): A 28-Year Perspective”. MEDICINE, 81:87-100, 2002.
“Number (in Thousands) of Hospital Discharges with Diabetic Ketoacidosis as First-Listed Diagnosis, United States, 1988–2009”. Center for Disease Control and Prevention.
http://www.cdc.gov/diabetes/statistics/dkafirst/fig1.htm. Accessed 9/20/12.
Kitabchi, et al. “Hyperglycemic Crises in Adult Patients With Diabetes”. Diabetes Care. 2009 Jul;32(7):1335-43.
Malek, et al. “Treatment of type b insulin resistance: A Novel Approach to Reduce Insulin Receptor Autoantibodies”. J Clin Endocrinol Metab, August 2010, 95(8):3641-3647.
Page, et al. “A patient with type B insulin resistance syndrome, responsive to immune therapy”. Nature Clinical Practice Endocrinology & Metabolism. December 2007, VOL 3 NO 12.