PO C. Evaluate individual patient needs based on age, developmental stage, family history, ethnicity, and individual risk.
PO D. Formulate a plan that addresses health promotion, anticipatory guidance, and/or disease prevention for the individual.
DOMAIN 1, COMPETENCY 3
Formulate differential diagnoses, and diagnostic strategies and therapeutic interventions with attention to scientifi c evidence, safety, cost, invasiveness, simplicity, acceptability, adherence, and effi cacy for patients who present with new conditions and those with ambiguous or incomplete data, complex illnesses, comorbid conditions, and multiple diagnoses in all clinical settings.
PO B. Formulate a differential diagnosis for a patient who presents with ambiguous or incomplete data, complex illnesses, comorbid conditions and potential multiple diagnoses.
PO C. Discuss the rationale for the differential diagnosis.
PO D. Discuss the rationale for the diagnostic evaluation with attention to scientifi c evidence, safety, cost, invasiveness, simplicity, acceptability, adher- ence, and effi cacy.
PO E. Discuss the rationale for the therapeutic intervention with attention to scientifi c evidence, safety, cost, invasiveness, simplicity, acceptability, adher- ence, and effi cacy.
Chapter 13 Adult Male With Ketosis-Prone Diabetes Mellitus
171
Identifying Information
Site: Urban academic medical center.
Setting: Inpatient hospital medical unit.
Reason for encounter: Consult requested by medical service for patient with diffi cult-to-control diabetes in preparation for discharge.
Informant: Chart review and patient who is a poor historian.
History of Present Illness
Mr. O is a 60-year-old Hispanic male with a history of diabetes (DM) found unresponsive at home by family. Emergency medical services (EMS) was called and upon arrival obtained fi ngerstick blood glucose (FSBG) of 34 mg/dl.
Tonic-clonic seizures were also noted. EMS transferred Mr. O to the emer- gency department (ED), and he was subsequently admitted to neurological intensive care unit (NICU).
While in the NICU, Mr. O was treated with Dextrose 10% infusion; FSBG was monitored every one hour. Hypoglycemia persisted for more than 24 hours. His seizures were controlled with phenytoin (Dilantin). An intrave- nous insulin infusion was started once FSBG was greater than 200 mg/dl. Mr. O was transferred to a medical unit where glargine (Lantus) 15 units daily and lispro (Humalog) with meals were initiated. Blood glucose was acceptable on this insulin regimen, but suboptimal with FSBG ranging from 122–280 mg/dl.
Repaglinide (Prandin) with meals was added, and lispro (Humalog) insulin with meals was discontinued. As a result, blood glucose levels became very elevated, ranging between 155 to 500 mg/dl. Consultation was requested of the inpatient DM team for discharge planning.
Diabetes History
The majority of this history was obtained through medical chart review. Mr. O is a poor historian.
At present, Mr. O denies weight changes, polydipsia, polyphagia, tempera- ture intolerance, changes in hair and skin texture, urinary frequency, urgency, hesitancy, dysuria, hematuria, polyuria, nocturia, and incontinence of urine.
Time Home Management Hospitalization
1993 Diagnosed with Type 2 DM in 1993, presentation unclear.
Treated with oral hypoglycemic agents for approximately fi ve years.
1998 Insulin initiated for questionable poor blood glucose control.
(continued)
Time Home Management Hospitalization
2003 (time zero) Hyperglycemia management included insulin lispro protamine/insulin lispro 75/25 (Humalog Mix 75/25) 40 units in AM, Glargine (Lantus) 20 units HS, and Pioglitazone (Actos)
Presented to hospital with fi rst episode of diabetic ketoacidosis (DKA).
For several days prior to his admission, he had stopped his insulin because he was having hypoglycemia.
He was discharged home on insulin NPH (Novolin N) 30 units in AM and 20 units in HS, and Glipizide XL (Glucotrol XL) 5 mg daily in A.M.
2003 (six months) Unclear home management.
Regimen was most likely consistent with medication prescribed at time of discharge six months prior.
Presented to hospital in DKA, with no evidence of acute illness or severe stress provoking the DKA.
Mr. O was discharged home on insulin NPH (Novolin N) 40 units in AM and 20 units HS.
2005 (24 months) Home hyperglycemia management at that time was Glargine (Lantus) 60 units and Metformin (Glucophage) 500 mg q daily.
Patient reported low FSBG in AM and high FSBG in PM on regimen.
Admitted for hypoglycemia.
Discharge medications: insulin NPH (Novolin N) 30 units in AM and 15 units in HS, and Lispro (Humalog) with meals.
2006 (31 months) Admitted for hypoglycemia.
Discharge medications: insulin NPH/regular 70/30 (Novolin 70/30), Rosiglitazone (Avandia), and Glimepiride (Amaryl).
2006 (37 months) Presented to hospital in DKA, with
no evidence of acute illness or severe stress provoking the DKA.
Discharge medication: insulin NPH/
regular 70/30 (Novolin 70/30) 20 units in AM and 15 units HS.
2006 (38 months) Readmitted for hypoglycemia.
Discharge medications: Glargine (Lantus) 30 units q daily.
(continued)
Chapter 13 Adult Male With Ketosis-Prone Diabetes Mellitus
173
Medical History
Diffuse Large B Cell Lymphoma diagnosed one year ago, status post four cycles of
•
chemotherapy. Now in remission.
Cardiomyopathy most likely secondary to chemotherapy with doxorubicin (Adriamy-
•
cin). Last transthoracic echocardiogram done one month ago showed ejection fraction 40%. Followed by cardiologist.
Diabetic retinopathy status post laser treatment. Last eye exam six months ago with
•
no progression.
DM with microalbuinuria treated with lisinopril (Prinivil).
•
Hypertension treated with lisinopril (Prinivil). Blood pressure well controlled for past
•
two years with recorded values ranging from 110–128/65–88.
Dyslipidemia treated with atorvastatin (Lipitor) 40 mg orally in the evening. Last lipid
•
panel one month ago: LDL 75, Triglycerides 152, HDL 36, total 140.
Non-ST elevation myocardial infarction in 2006 with triple-vessel disease. Followed
•
by cardiologist. Currently denies chest pain, orthopnea, dyspnea on exertion, postural nocturnal dyspnea, peripheral edema, leg cramps with walking a specifi c distance, or palpitations.
Psoriasis. Currently denies
• rash, pruritus, dryness, non-healing wounds or lesions.
Home Medications (see also Medications list at the end of the chapter)
Lisinopril (Prinivil) 5 mg orally daily.
•
Digoxin (Digitek) 0.125 mg orally daily.
•
Carvedilol (Coreg) 6.25 mg orally twice daily.
•
Atorvastatin (Lipitor) 40 mg orally at bedtime.
•
Aspirin (Ecotrin) 325 mg orally daily.
•
Furosemide (Lasix) 40 mg orally daily.
•
Glargine (Lantus) 50 units subcutaneously daily.
•
Rosiglitazone (Avandia) 4 mg orally daily.
•
Time Home Management Hospitalization
2006 (49 months) Mr. O presented to the hospital in
hyperosmolar hyperglycemic non-ketosis (HHNK). He was discharged home on Glargine (Lantus) 35 units, As an outpatient, Mr. O’s Glargine (Lantus) dose was slowly increased to 50 units due to blood glucoses of 500 mg/dl, and Rosiglitazone (Avandia) 4mg q daily was added.
2007 (50 months) Presents to hospital with
hypoglycemia and seizures.
Social History
Mr. O is a Hispanic unemployed former taxi driver who lives alone. He denies currently smoking. He stopped one year ago, but has a 40-pack- per-year history. He denies alcohol or illicit drug use. He is independent in his mobility, but has a home health attendant six hours a day, seven days a week, to help him with his activities of daily living, including cooking and shopping.
Review of Systems
Skin: See “Medical History.”
Eyes: Denies changes in visual fi elds, blurred vision, fl oaters, glaucoma, or cataracts.
Respiratory: Denies chest pain, dyspnea, cough, or shortness of breath.
Cardiovascular: See “Medical History.”
Gastrointestinal: Denies dysphagia, nausea or vomiting, diarrhea, or abdominal pain.
Endocrine: See “History of Present Illness.”
Family History
DM, MI 56 y DM, MI
61 y
Unknown
Unknown Unknown Unknown Unknown
DM
Alive and well
52 y 60 y
DM Psoriasis Diffuse Large B cell
Lymphoma HTN Cardiomyopathy
NSTEMI
Dyslipidemia No consanguinity
Ethnicity: Hispanic
Chapter 13 Adult Male With Ketosis-Prone Diabetes Mellitus
175
Urology: See “History of Present Illness.”
Peripheral vascular: See “Medical History.”
Physical Examination
General: 60-year-old Hispanic male who appears stated age, minimally responsive, and is in no acute distress.
Vital signs: Pulse 90, respirations 18, blood pressure 125/67, height 167.6 cm, weight 64.5, BMI 23.
Neck: No enlarged lymph nodes or thyromegally appreciated.
Chest: Breath sounds are clear bilaterally, anteriorly, and posteriorly, without rales, rhonchi, wheezes, or rubs.
Heart: Regular rate and rhythm, S1, S2, no murmurs, rubs, or gallops.
Peripheral vascular: No cynanosis, clubbing, or edema. Decreased monofi la- ment sensation bilateral plantar aspect of feet.
Labs Patient Result Normal Values
Cr 1.31.3 0.5–0.9 mg/dl
K 5.15.1 3.6–5.0 mM/l
AST 23 12–38 U/l
ALT 17 7–41 U/l
Urine microalbuminuria (UMA) 847847 <30 ug/mg creatinine
C-peptide <0.5<0.5 0.8 to 3.5
Glutamic acid decarboxylase 0.08 0.00 to 1.45
Islet cell autoantibodies <1:4 <1:4
A1c Now: 9.1
2007: 9.1
2003–2006: 7.9–11.97.9–11.9 4–6%
It is important to consider renal function when considering how to treat a patient with diabetes. Renal insuffi ciency contributes to abnormalities affecting glucose and insulin metabolism. While there is augmented hepatic gluconeogenesis, there is diminished renal gluconeogenesis. There is also decreased level of degradation of insulin in peripheral tissues. Exogenous insulin is primarily excreted by the kidney. As renal failure progresses, insulin clearance decreases, the half-life of insulin increases, and the overall require- ments of insulin decline (Biesenbach et al., 2003).
Oxford Centre for Evidence-Based Medicine (CEBM), level 2b.
Since hepatic impairment can lead to reduced insulin metabolism and reduced hepatic gluconeogenesis, it is important to consider liver function in treating a patient with diabetes.
The normal rate of albumin excretion is less than 20 mg/day (15 µg/min);
persistent albumin excretion between 30 and 300 mg/day (20 to 200 µg/
min) is called microalbuminuria and, in patients with diabetes (particularly type 1 diabetes), is usually indicative of diabetic nephropathy unless there is some coexistent renal disease. Values above 300 mg/day (200 µg/min) are considered to represent overt proteinuria. Although these cut-offs defi ning normoalbuminuria, microalbuminuria, and overt proteinuria facilitate deter- mining the risk for progression of nephropathy, the risk of developing overt diabetic nephropathy is probably linearly related to albumin excretion rates at all levels (Mogensen, 1990).
CEBM, level 5.
GAD and ICA are not generally recommended for diagnosis for diabe- tes. However, in order to distinguish between autoimmune diabetes and non-autoimmune diabetes, obtaining GAD and ICA, as well as a C-peptide appears to be the best for determining the type of diabetes a patient has (Balasubramanyam, 2006).
CEBM, level 5.
Impression
Mr. O is a 60-year-old Hispanic male with unclear type of diabetes with multiple episodes of DKA and hypoglycemia. Upon inquiry I fi nd that Mr. O has a long history of diabetes and is familiar with the skills necessary for adequate measurement, and therefore has insight about his diagnosis of type 2 DM and its management. There is no reason to suspect that he gave himself too much insulin or is noncompliant with his DM management.
Moreover, based on his laboratory results demonstrating negative GAD and negative C-peptide, a diabetes history of multiple admissions with DKA and hypoglycemia resulting from overdosing of basal insulin needs, family history, and ethnicity, he likely has what the American Diabetes Association (ADA) would classify as idiopathic DM, also known as type 1B DM from beta-cell dysfunction, and will need to be managed on subcutaneous insulin injections for blood glucose control. Mr. O’s failing to take his oral hypergly- cemic medications helps confi rm this diagnosis(D1, C1, PO C; D1, C3, PO B, C, D, E).
Patients with idiopathic DM do not have the autoantibodies seen in type 1 DM, but are prone to ketoacidosis for unclear reasons. New evidence would classify Mr. O as having ketosis-prone DM type 1B (Maldonado et al., 2003) (D1, C1, PO B; D1, C3, PO C). His hypoglycemia likely resulted because his glargine dose was increased beyond his basal needs, rather than adding a bolus regimen to the patient’s insulin regimen (D1, C3, PO D, E).
Chapter 13 Adult Male With Ketosis-Prone Diabetes Mellitus
177
Critical Appraisal
In terms of interventions for Mr. O’s DM management, it is important to attempt to classify more defi nitively what type of DM he has to help optimize his glycemic control. Since DKA is the most serious hyperglycemic emergency in patients with diabetes, it is important to isolate the reason why patients present in DKA. Gen- erally there are precipitating factors that cause DKA. However, in recent years there have been an increasing number of cases of DKA without precipitating factors, and much attention has been given to attempt to describe these cases (Umiperrez, 2006). Clinical heterogeneity of certain presentations of diabetes in multiethnic populations has signifi cant implications for diagnosis, classifi cation, and management (Balasubramanyam, et al., 2006) (D1, C1, PO A).(D1, C1, PO A).
CEBM, level 5.
The two broad categories of DM defi ned by the ADA are designated type 1 and type 2. However, for patients with type 1 DM, the most common reason for patients to present in DKA is subdivided into type1A and type1B (idiopathic) (ADA, 2009). Type 1A DM results from autoimmune b-cell destruction, as a result of a defect of an HLA allele, which leads to insulin defi ciency. Individu- als with type 1B DM lack an HLA genetic marker and immunologic markers indicative of an autoimmune destructive process of the b-cells. However, they develop insulin defi ciency by unknown mechanisms and are ketosis prone.
Recently, emerging data has shown that the ADA’s defi nition of “idiopathic”
diabetes is far too simplistic especially among non-Caucasian populations (Balasubramanyam, 2006). There is a high proportion of DKA in nonwhite adults that occurs in persons with type 2 DM (Balasubramanyam, Zern, Hyman, & Pavlik, 1999).
CEBM, level 5.
It is thought that there is a genetic susceptibility to ketosis prone DM, but it is not certain whether there are multiple genetic markers or just one major gene that leads to a defect in b-cell secretion (Mauvais-Jarvis et al., 2004).
Ketosis-prone patients demonstrate that the presence or absence of islet cell autoantibodies or HLA susceptibility alleles are not necessarily the key determinants in b -cell function (Balasubramanyam et al., 2006). Ketosis- prone diabetes (KPD) is heterogeneous. Its causes could include novel b-cell functional defects. In order to improve outcomes of KPD patients, several studies have attempted to predict long-term b-cell function and insulin independence in patients with DKA. Of several methods to defi ne KPD heterogeneity, the A b scheme is the most accurate in predicting long-term b-cell function and clinical outcomes (Balasubramanyam et al., 2006). A study done by an endocrinology group out of Baylor College of Medicine took 103 patients who presented with DKA and analyzed their b-cell func- tion, b-cell autoimmunity, and HLA genotype. Maldonado et al., classifi ed
these patients into four Ab groups, based on the presence of glutamic acid decarboxylase (GAD)65, GAD67, or islet cell autoantibodies (A+ or A-) and b-cell functional reserve (b+ orb-). It is believed that KPD comprises at least four etiologically distinct syndromes separable by autoantibody status, HLA genotype, and b-cell functional reserve. Novel, nonautoimmune, polygenetic causes of b-cell dysfunction are likely to underlie the A-b+ and A-b- syn- dromes (Maldonado et al., 2003).
CEBM, level 2b.
β– (β-cell function –) β+ (β-cell function +)
A+ (autoimmunity +) KPD type 1A.
These are A+β– patients.
They have permanent and completeβ-cell failure with serologic markers of islet cell autoimmunity and HLA genetic marker. They require lifelong exogenous insulin therapy. Usually lean build, no strong family history.
KPD type 2A.
These are A+β+ patients. They have preserved β-cell function at the time of diagnosis but also have serologic markers of islet cell autoimmunity and HLA genetic marker. Some have a reversible form of β-cell dysfunction, characterized by prolonged preservation of β-cell function and ability to discontinue exogenous insulin therapy, while others have progressive β-cell failure and require lifelong exogenous insulin therapy. Usually obese, strong family history of T2DM, variant of LADA.
A– (autoimmunity –) KPD type 1B.
These are A–β– patients.
They have permanent and completeβ-cell failure but lack serologic markers of islet cell autoimmunity and lack HLA. They require lifelong exogenous insulin therapy. Usually non-obese, strong family history, non- white, may have variable insulin requirements.
KPD type 2B.
These are A–β+ patients. They have preserved β-cell function and lack serologic markers of islet cell autoimmunity. The majority (especially if new onset) can discontinue exogenous insulin therapy. Usually a strong family history of Type 2 DM, obese, DKA at presentation but no recurrence, Flatbush; atypical DM; type 3 KPD.
A Beta Symbol Scheme
Chapter 13 Adult Male With Ketosis-Prone Diabetes Mellitus
179
Plan (D1 C1, PO D)
HgA1c in three months that will be used, in addition to FSBG log book, to
•
assess glycemic control.
Critical Appraisal
Now that likely ketosis-prone type 1B DM has been the identifi ed cause of Mr. O’s multiple admissions, the goal is to reduce the number of admissions for DKA and hypoglycemia to zero. Once that goal has been achieved, the next goal will be that his HgA1c is less than 7%.
Ophthalmology referral
• (D2, C2, PO A).
ADA recommends an ophthalmology examination once a year to monitor for diabetic retinopathy (ADA, 2009).
CEBM, level 5.
Discharge patient on glargine (Lantus) 15 units subcutaneous daily and
•
lispro (Humalog) six units with meals.
Discontinue oral hypoglycemic agents. Since Mr. O has no beta-cell func-
•
tion, as evidenced by his near-negative C-peptide, there is little evidence to suggest that oral antihyperglycemic medications will be effective for DM management(D1, C3, PO E).
DM self-management education reinforcement:
•
“Survival Skills”: Diabetes education given to Mr. O regarding –
self-monitoring BG before each meal and before bed, target BG of 120–180 mg/dl, emergency BG values greater than 240 mg/dl each time a BG is checked for two consecutive days or one time BG greater than 400 mg/dl, basal versus bolus insulin-time-action profi le of the two different insulins, reviewed hypoglycemic and hyperglycemic symptoms, preven- tion, and treatment, and consistent carbohydrate diet.
Education by hospital nutritionist and reinforced by me included exer- –
cise as tolerated, and the importance of following up with the inpatient diabetes nurse practitioner until seen by an endocrinologist at the dia- betes center.
Written information given to Mr. O
– (D2, C2, PO E).
Teaching diabetes self management to hospitalized patients is a diffi cult and challenging task. Patients are hospitalized because they are ill, under increased stress, and in an environment that is not conducive to learning (ADA, 2009). They often have competing concerns related to their hospi- talization, are being seen by many providers, and fundamentally, are not focused on learning all that there is to gain knowledge of appropriate diabe- tes self-management skills. Trying to teach everything there is to know about diabetes can be overwhelming to inpatients especially if diabetes is not the
primary reason for admission. Since there are usually competing priorities, limited time, and an ill-conducive learning environment, the primary focus for diabetes self-management should be on those skills that are essential and suffi cient for the patient to go home safely (Clement, 2004). Many clinicians refer to this as diabetes “survival skills” education. For patients who have a new diagnosis or have had little previous education, it generally means the following:
1. Understanding the disease and its treatment
2. Understanding how to manage diabetes medications, including injecting insulin, with special emphasis on any changes made to a prior regimen 3. Understanding how to monitor blood glucose and target blood glucose
values
4. Understanding how to recognize and treat high and low blood glucose 5. Understanding the importance of follow up care, when to contact their
healthcare provider or go to the emergency department (Nettles, 2005).
CEBM, level 5.
Order visiting nursing service to reinforce DM self-management education
•
(D2, C2, PO E).
Follow-up appointment in one to two weeks at diabetes center. I called
•
outpatient endocrinologist regarding inpatient management and outpatient instructions(D2, C2, PO C, D).
ICD-9 code:
• 250.93 Diabetes with unspecifi ed complication type 1 uncontrolled.
COMPETENCY DEFENSE
Domain 1, Competency 1. Evaluate patient needs based on age, developmen- tal stage, family history, ethnicity, individual risk, including genetic profi le to formulate plans for health promotion, anticipatory guidance, counseling, and disease prevention services for healthy or sick patients and their families in any clinical setting.
Domain 1, Competency 3. Formulate differential diagnoses, and diag- nostic strategies and therapeutic interventions with attention to scientifi c evidence, safety, cost, invasiveness, simplicity, acceptability, adherence, and effi cacy for patients who present with new conditions and those with ambigu- ous or incomplete data, complex illnesses, comorbid conditions, and multiple diagnoses in all clinical settings.
Defense. Competency 1 and Competency 3 were met because Mr. O has a strong family history with an ambiguous presentation of DM that indicated there was a risk for a potential genetic condition and a differential diagno- sis needed to be formulated. Through comprehensive literature review and diagnostic tests, a diagnosis was made, and an appropriate management plan was formulated. The plan includes health promotion through a more appropriate understanding of his disease, and will likely improve his glyce- mic control.