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40 The Nurse Practitioner -  Vol. 41, No. 5
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Adult diabetes mellitus: Thinking beyond type 2
Copyright (c) 2016 Wolters Kluwer Health, Inc. All rights reserved.
Adult diabetes mellitus:
Thinking beyond type 2
Abstract: Not all adults presenting with diabetes mellitus have type 2. NPs
must become familiar with atypical presentations of type 1 and type
2 diabetes mellitus, especially in light of the current endocrinologist
shortage. Two case studies illustrate variations of adult-onset diabetes
along with discussion and diagnostic clues.
By Karla K. Giese, DNP, FNP, BC-ADM, CDE
T
he CDC estimates that 12.3% of individuals in the
United States age 20 and older have diabetes mellitus.
Broken down by age group, 25.9% of those age 65 and
older (typically Medicare eligible), and 16.2% of adults ages 45
to 64, have diabetes.1 The vast majority of diabetes mellitus care
(hereafter simply referred to as diabetes) is received in primary care
settings, where the majority of NPs care for patients.2,3 DesRoches
and colleagues demonstrated that the largest number of NPs
per 1,000 Medicare benefciaries were practicing in rural states,
and NPs were more likely than physician colleagues to care for
underserved populations  as evidenced by an increased patient
load with dual Medicare/Medicaid eligibility.4
Mundinger and colleagues frst demonstrated equivalent pri
mary care between NPs and their physician colleagues.5 A recent
systematic review and meta-analysis confrmed the same f ndings:
Primary care NPs have consistently demonstrated equivalent
primary care compared with physician primary care providers
(PCPs).6 Therefore, healthcare consumers have the choice of
receiving care from NPs-who demonstrate equivalent care as
discussed-but with the added advantage of holistic approaches to
care, communication skills (particularly with patients), promotion
of patient-centered self-management, and subspecialty expertise
in chronic disease management.7
OKSIPIX / ISTOCK (c)
Keywords: diabetes management, diabetes mellitus, ketosis-prone diabetes, latent autoimmune diabetes, nurse practitioner
40 The Nurse Practitioner -  Vol. 41, No. 5
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Adult diabetes mellitus: Thinking beyond type 2
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T1DM and LADA are frequently associated
with normal to low body weight and/or
significant weight loss at presentation.

Copyright (c) 2016 Wolters Kluwer Health, Inc. All rights reserved.
Adult diabetes mellitus: Thinking beyond type 2
Improved access to care through the Affordable Care
Act (ACA) has contributed to identifying previously un
diagnosed diabetes.8 Additionally, based on this author's
experience in a private NP-managed diabetes clinic, expand
ing health coverage through the ACA has enabled patients
with diabetes previously in safety-net care settings, those
with signifcant gaps in health coverage, and those recently
released from incarceration to enter the private primary
care offces, often with signifcantly advanced disease. Dia
betes cases continue to rise in other private sectors as well.
Burgeoning diabetes caseloads, coupled with a nationwide
shortage of endocrinologists, have created a critical need for
expert-level diabetes care among NPs as well as an improved
knowledge base for primary care NPs.9
Approximately 90% of diabetes cases are type 2 diabetes
mellitus (T2DM).1 Of these cases, a substantial number of
individuals (estimated at 10%) are positive for pancreatic
autoantibodies characteristic of type 1 diabetes mellitus
(T1DM).10 T1DM, including both autoimmune and idio
pathic, make up the second largest category behind T2DM.
Although most commonly associated with childhood onset,
literature from Sweden has reported that approximately 25%
of T1DM cases are diagnosed as adults.11 A vast number of
less common types of diabetes, including secondary to exo
crine pancreatic disease (such as cystic f brosis), monogenic
diabetes syndromes (such as maturity-onset diabetes), drug-
induced diabetes, chemical-induced diabetes, and other
variants, make up the remaining nongestational cases.12
This article highlights clinical presentations of two
atypical types of adult diabetes: ketosis-prone diabetes
(KPD) and latent autoimmune diabetes in adults (LADA).
Diagnostic clues and testing are discussed in an effort to
arrive at the best diagnostic classif cation, promoting the
most appropriate glucose-lowering regimen for improved
patient outcomes.
 Case one
Mr. G, 30, is a Black male with class 3 obesity (body mass
index [BMI] 45) who presents to the primary care off ce
1 week post ICU hospitalization for follow-up diabetic
ketoacidosis (DKA), new-onset T2DM, and dental abscess.
He has no history of unintended weight loss, but his his
tory is positive for urinary frequency, thirst, blurred vision,
and fatigue over the last few months. Severe dental pain
precipitated the ED visit.
Mr. G's medical history is positive for obesity for many
years, and his family history is positive for T2DM and
obesity. Admission hospital labs were signifcant for large
urine ketones, positive serum acetone, and hemoglobin
A1C (A1C) of 12.7%. The dental abscess was treated with
I.V. antibiotics, DKA was corrected,
and he was subsequently discharged
to primary care follow-up with a di
agnosis of T2DM and treatment with
basal insulin.
A diabetes-related autoantibody
panel was run, including islet cell
autoantibody (ICA), glutamic acid
decarboxylase-65 autoantibody (GAD-65A), and insulin
autoantibody (IAA). An insulinoma-associated-2 auto-
antibody (IA-2A) is also included in this panel for some
labs, but not the lab used in this case. A fasting C-peptide
and fasting blood glucose were also obtained. Results
showed a normal C-peptide, elevated fasting blood glu
cose (235 mg/dL), negative ICA, negative GAD-65A, and
negative IAA.
 Case two
Ms. M, 49, is a White female who presents to her PCP
with a 30-lb (13.6 kg) unintentional weight loss, palpita
tions, hot fashes, anxiety, and thirst over the last 6 months.
She has no family history of diabetes, and her presenting
BMI is 21.60. Initial labs included a fasting blood glucose
level of 325 mg/dL and otherwise normal chemistry panel,
small urine ketones, and an A1C of 12%. An urgent refer
ral to the diabetes clinic was made. Labs from the diabetes
clinic included a markedly elevated GAD-65A, markedly
elevated antithyroid peroxidase (TPO) antibody, elevated
thyroid-stimulating hormone (TSH) receptor antibody,
suppressed TSH, free thyroxine (FT4) 1.5 ng/dL, and C-
peptide 0.9 ng/mL.
 Diagnosis and diagnostic clues
Diabetes (nongestational) is diagnosed by repeat testing
(in the absence of unequivocal hyperglycemia) based on a
fasting plasma glucose of 126 mg/dL or greater, or an A1C
of 6.5% or greater, or a 2-hour plasma glucose of 200 mg/dL
or greater during an oral glucose tolerance test, or a random
plasma glucose of 200 mg/dL or greater with symptoms of
hyperglycemia.12 The American Diabetes Association (ADA)
classifes diabetes typology into four main categories based
on underlying mechanisms: T1DM (indicating absolute in
sulin defciency); T2DM (characterized by insulin resistance
and progressive beta cell dysfunction); gestational diabetes
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Copyright (c) 2016 Wolters Kluwer Health, Inc. All rights reserved.
Adult diabetes mellitus: Thinking beyond type 2
(typically diagnosed in the second or third trimester); and
other cause of diabetes, as previously mentioned.12
Age of onset, body habitus, and presence/absence of
ketones are not diagnostic criteria for diabetes. However,
age at diagnosis can provide clues, since most autoimmune
diabetes presents in either childhood (T1DM) or earlier
adulthood in the slowly progressing form of T1DM known
as LADA.
Body habitus offers a diagnostic clue because a large
percentage of T2DM is associated with obesity. T1DM and
LADA are more frequently associated with normal to low
body weight and/or signifcant weight loss at presentation.
Presence of ketones or DKA (a common problem in T1DM)
provides an additional, although nondiagnostic, clue to
diabetes classif cation.
 Ketosis-prone diabetes
KPD is a subtype of T2DM seen in patients primarily of
African, Hispanic, or Asian descent.13 This nonautoimmune
subtype presents acutely with very high blood glucose levels
and ketones with or without acidosis, and is more common
(although not exclusively) in obese males.13 Glucose toxicity,
manifested as extremely high blood glucose; unintentional
weight loss; extreme, unquenchable thirst; urinary fre
quency; and fatigue at presentation are common. Umpierrez
and colleagues demonstrated that the acute glucose toxic
presentation of KPD blunts beta cell functioning, but is
reversible.14
Choukem and colleagues further demonstrated a re
sidual dual defect of reduced beta and alpha cell function,
resulting in impaired insulin secretion and impaired gluca
gon suppression in patients with KPD even after normogly
cemia was achieved.15 Diagnostic clues to KPD include the
symptoms of glucose toxicity discussed above, coupled with
ketosis and/or DKA, negative diabetes-related autoantibod
ies, and a normal C-peptide.16
Reversible (yet still reduced) beta cell dysfunction sug
gests that exogenous insulin administration may not be nec
essary for an extended period of time.14,15 Insulin therapy is
used initially; however, based on this physiology, once acute
glucose toxicity is stabilized with insulin therapy, lifestyle
measures and metformin plus additional pharmaceutical
intervention targeting beta and alpha cell dysfunction-such
as glucagon-like peptide-1 (GLP-1) receptor agonists and/
or sulfonylureas-would be appropriate based on glucose
levels.15
 Latent autoimmune diabetes in adults
LADA is an immune-mediated, antibody-positive type of
diabetes.17 Exact labeling has been somewhat confusing
because many patients are initially diagnosed as T2DM until
Autoantibodies associated with autoimmune
diabetes21,22
Islet cell autoantibody testing is very helpful in diagnos
ing autoimmune diabetes, such as LADA and T1DM.
Autoantibodies include:
-  Islet cell cytoplasmic autoantibodies (ICA)
(normal <1:4; no antibody detected)
-  Glutamic acid decarboxylase-65 autoantibody
(GAD-65A) (normal 0.0-5.0 IU/mL)
-  Insulinoma-associated-2 autoantibody (IA-2A)
(normal 0.0-0.8 units/mL)
-  Insulin autoantibodies (IAA) (normal 0.0-0.4 units/mL)
-  Zinc transporter 8 (ZnT8A) autoantibodies: Available
in research settings and in some facilities (normal
0.0-15.0 units/mL)
an astute clinician recognizes nonresponse to traditional
T2DM therapy and checks islet cell antibodies. (See Auto-
antibodies associated with autoimmune diabetes.) Current
guidelines classify LADA as a subtype of T1DM due to its
autoimmune state.12 The Immunology of Diabetes Society
suggests three important criteria for LADA: age of at least 30,
positive for at least 1 antibody, and not requiring insulin for
glucose control the frst 6 months of the disease state.18 The
ICD-10 Manual does not have a code for LADA; therefore,
coding could fall under the E10 category, "type 1 diabetes
mellitus."19
Progressive, immune-mediated beta cell destruction
within the pancreas is accelerated, leading these patients to
require insulin replacement. Unintended weight loss and
ketosis are signs of significant beta cell destruction and
should prompt a quick reanalysis of any previously diag
nosed patient with T2DM. Clues to diagnosing LADA may
include a "younger" adult (although late in life is still pos
sible) inadequately responding to typical T2DM therapies;
relatively normal body weight, personal or family history of
autoimmune illnesses (such as autoimmune hypothyroid
ism or hyperthyroidism), Addison disease, or celiac disease;
ketosis; and unintended weight loss (see Atypical diabetes
types). Patients with LADA will typically (eventually) require
basal (long-acting/background) and prandial (mealtime)
insulin due to beta cell destruction. In addition, evidence
suggests that earlier treatment with insulin therapy leads to
improved metabolic control.20,21
Returning to the case studies presented, case one, rep
resenting Mr. G, depicts KPD with antibody negative status
and normal C-peptide. Basal and prandial insulin were used
for 3 months, allowing the glucose toxicity to abate and
pancreatic function to return. Over the subsequent months,
metformin and a once-weekly GLP-1 agonist were added
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Copyright (c) 2016 Wolters Kluwer Health, Inc. All rights reserved.
Adult diabetes mellitus: Thinking beyond type 2
Atypical diabetes types13-18
Diabetes type
Ketosis
Antibodies
KPD
+
-
LADA
+
+
Key: + = present, - = absent,  = normal,  = decreased.
Obese
+
-
Acute onset
+
-
Family history of diabetes
+
+
C-peptide


while simultaneously titrating off insulin. Mr. G will remain
vulnerable to ketosis in times of illness, and NPs must watch
for further deterioration of beta cell function. His last A1C
was within the ADA goal (less than 7%), at 6.8%.12
Case two, representing Ms. M, deals with a woman
who for unclear reasons developed two autoimmune dis
ease processes simultaneously: LADA, as evidenced by the
markedly elevated GAD-65A antibody, low C-peptide, and
ketonuria, in addition to Graves disease as evidenced by the
markedly elevated TPO antibody, elevated TSH receptor
antibody, and suppressed TSH. Although hot f ashes could
be related to perimenopause, they resolved with Graves
disease treatment.
Insulin therapy is clearly indicated in case two; however,
there is not one right way to initiate insulin. Evidence-based
practice includes scientifc evidence in addition to clinical
experience and patient values and preferences.23 Therefore,
patient factors, such as meal patterns, willingness toward
injection frequency, anxiety level, social support, education
level, and insurance coverage, must all be considered in
choosing an insulin regimen. The ADA suggests initiating
insulin at 0.4 to 1.0 unit/kg/day with one-half to two-thirds
used for basal (background) coverage, and the other one-
third to one-half divided for meal coverage.24
Ms. M was started on a total daily insulin dose at 0.4 unit
per kg body weight, with half (10 units) basal at bedtime
and the other half as a prandial (mealtime) rapid-acting
analogue insulin dose of 3 units before breakfast, lunch, and
dinner. Fixed mealtime doses were chosen for Ms. M due to
her high anxiety level with the initial diagnosis in addition
to consistent, highly predictable meals.
Concomitant with the diagnosis and insulin initiation
was an important standard of care in any patient with newly
diagnosed diabetes (or in cases of diabetes where therapy
has changed): referral to a certifed diabetes educator (CDE)
for comprehensive diabetes self-management education
(DSME) and teaching of home blood glucose monitoring.23
Education about carbohydrate counting may enable a more
intensive insulin regimen based on meal carbohydrate con
tent in the future. Ms. M's most recent A1C was 6.5%, her
anxiety was markedly improved, and the patient's self-care
and self-confdence were strong.
 When to refer
Self-refection in evaluating an NP's knowledge and man
agement skills around diabetes care is helpful for personal
growth and patient safety. A mentor early in the author's
own career once warned of "not knowing what you don't
know." A tongue twister, yes, but if an NP does not know of
a disease process, it cannot be properly addressed. Engag
ing in continuing education through professional journal
reading, conference attendance, and networking, along with
active clinical practice, contributes to an NP's expanding
knowledge base.
Patient safety is always frst. In cases with a perplexing
diagnosis or diabetes management, NPs should refer to a
diabetes specialty-level NP clinician likely holding a CDE
and/or board certifed advanced diabetes management cre
dential, or an endocrinologist. Preferable referral centers
will have a nationally accredited DSME program for initial
and ongoing support. Similarly, for those patients who are
not responding to therapy, reevaluation of the diagnosis,
including lifestyle and medication adherence, is crucial.
 Moving forward
NPs must be alert for cases of atypical diabetes, such as
KPD and LADA/slowly progressing T1DM, and proactively
prepare to diagnose and treat such cases appropriately for
improved outcomes. An urgent need exists for NPs with
specialty level skills in diabetes management due to a con-
f uence of factors, including the endocrinology physician
shortage, epidemic obesity rates with resultant diabetes,
and patient desire for NP care. The ADA (www.diabetes.
org) and the American Association of Diabetes Educators
(www. diabeteseducator.org) have additional resources for
NPs ready to further enhance knowledge of diabetes care.
REFERENCES
1. Centers for Disease Control and Prevention. National diabetes statistics
report: estimates of diabetes and its burden in the United States. 2014. www.
cdc.gov/diabetes/pubs/statsreport14/national-diabetes-report-web.pdf.
2. Centers for Disease Control and Prevention. Ambulatory care visits and
physician offce use. 2014. www.cdc.gov/nchs/fastats/physician-visits.htm
and www.cdc.gov/nchs/data/ahcd/combined_tables/AMC_2009-2010_com
bined_web_table01.pdf.
3. Spetz J, Fraher E, Li Y, Bates T. How many nurse practitioners provide
primary care? It depends on how you count them. Med Care Res Rev.
2015;72(3):359-375.
44 The Nurse Practitioner -  Vol. 41, No. 5
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Copyright (c) 2016 Wolters Kluwer Health, Inc. All rights reserved.
Adult diabetes mellitus: Thinking beyond type 2
16. Grant P, Velusamy A, Thomas E, Chakera AJ. When to suspect 'funny' diabe-
tes. Clin Med (Lond). 2014;14(6):663-666.
17. Hernandez M, Mollo A, Marsal JR, et al. Insulin secretion in patients with
latent autoimmune diabetes (LADA): half way between type 1 and type 2
diabetes: action LADA 9. BMC Endocr Disord. 2015;15:1.
18. Naik RG, Brooks-Worrell BM, Palmer JP. Latent autoimmune diabetes in
adults. J Clin Endocrinol Metab. 2009;94(12):4635-4644.
19. American Medical Association. 2015 ICD-10 CM: The Complete Off cial
Codebook. Chicago, IL: AMA; 2014.
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Eur J Endocrinol. 2011;164(2):239-245.
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Karla Giese is the clinical provider and co-manager along with a dietitian at
Lovelace Medical Group/Southwest Medical Associates Diabetes and Metabo-
lism Clinic, Albuquerque, N.M. and an  in the DNP and MSN
programs at Liberty University, Lynchburg, Va.
The author has disclosed that she has a fnancial relationship with the following
companies: Eli Lilly and Astra Zeneca. This article has been reviewed, and all
potential or actual conficts have been resolved.
DOI-10.1097/01.NPR.0000482377.37112.be
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4. DesRoches CM, Gaudet J, Perloff J, Donelan K, Iezzoni LI, Buerhaus P. Us
ing Medicare data to assess nurse practitioner-provided care. Nurs Outlook.
2013;61(6):400-407.
5. Mundinger MO, Kane RL, Lenz ER, et al. Primary care outcomes in patients
treated by nurse practitioners or physicians: a randomized trial. JAMA.
2000;283(1):59-68.
6. Martinez-Gonzales NA, Tandjung R, Djalali S, Huber-Geismann F, Markun
S, Rosemann T. Effects of physician-nurse substitution on clinical param
eters: a systematic review and meta-analysis. PLoS One. 2014;9(2):e89181.
7. Watts SA, Gee J, O'Day ME, et al. Nurse practitioner-led multidisciplinary
teams to improve chronic illness care: the unique strengths of nurse prac
titioners applied to shared medical appointments/group visits. J Am Acad
Nurse Pract. 2009;21(3):167-172.
8. Kaufman HW, Chen Z, Fonseca VA, McPhaul MJ. Surge in newly identif ed
diabetes among Medicaid patients in 2014 within Medicaid expansion states
under the Affordable Care Act. Diabetes Care. 2015;38(5):833-837.
9. Vigersky RA, Fish L, Hogan P, et al. The clinical endocrinology workforce:
current status and future projections of supply and demand. J Clin Endocri
nol Metab. 2014;99(9):3112-3121.
10. Turner R, Stratton I, Horton V, et al. UKPDS 25: Autoantibodies to islet-cell
cytoplasm and glutamic acid decarboxylase for prediction of insulin re
quirement in type 2 diabetes. UK Prospective Diabetes Study Group. Lancet.
1997;350(9087):1288-1293.
11. Thunander M, Petersson C, Jonzon K, et al. Incidence of type 1 and type
2 diabetes in adults and children in Kronoberg, Sweden. Diabetes Res Clin
Pract. 2008;82(2):247-255.
12. American Diabetes Association. Standards of Medical Care in Diabetes-2016.
Diabetes Care. 2016;39:S1-S113.
13. Wang X, Tan H. Male predominance in ketosis-prone diabetes mellitus.
Biomed Rep. 2015;3(4):439-442.
14. Umpierrez GE, Smiley D, Gosmanov A, Thomason D. Ketosis-prone type 2
diabetes: effect of hyperglycemia on beta-cell function and skeletal muscle
insulin signaling. Endocr Pract. 2007;13(3):283-290.
15. Choukem SP, Sobngwi E, Boudou P, et al. - and -cell dysfunctions in
Africans with ketosis-prone atypical diabetes during near-normoglycemic
remission. Diabetes Care. 2013;36(1):118-123.
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