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CASE STUDIES

Case Study: and Early-Onset Type 1

Christian D. Herter, MD, CDE

Presentation C.B. received no nutrition informa- Commentary C.B., a 24-year-old woman, came to tion, but her mother taught her carbohy- Patients with type 2 diabetes are almost our clinic for a diabetes consultation drate counting. They were told that always obese (>20% over IBW). As after being referred by her mother, who metformin was the treatment choice but discussed in a previous issue of is one of our regular patients and has would not be started until our office Clinical Diabetes by Hansen et al.,1 type 1 diabetes herself. The older suggested it. obesity and family history of obesity woman’s diagnosis was made else- Besides being 3 weeks late with her are present in virtually all patients with where 7 years before she sought care menstrual period and having some type 2 diabetes. This is perhaps the with our office and had been based on tenderness, C.B. had no other most important risk indicator when her lean frame (5% below ideal body symptoms of pregnancy. Her mother considering the diagnosis. Patients with weight [IBW] based on height) at pres- was the only family member with dia- type 2 diabetes not only have a strong entation and relatively normal insulin betes of any type. C.B. and her husband family history of the disease,2 but also sensitivity (insulin requirements have had been trying to conceive for the past frequently have family members with a always been <0.5 U/kg/day). No anti- 3 months. preponderance of macrovascular condi- body studies or C-peptide levels were On exam, C.B. was a pleasant tions. done at the time of diagnosis. young woman with a weight of 67 kg People with type 1 diabetes are not Her daughter, C.B., was diagnosed and a height of 147 cm (IBW = 65 kg, usually obese and typically do not pres- with type 2 diabetes at a community therefore only 3% over IBW). Except ent with a clear family history of the clinic in a rural area near Seattle 3 for mild bilateral thyromegally, her disease. Often, there is weight loss at weeks before her visit with us. The physical exam was normal. Her home diagnosis, which is seldom a feature of diagnosis was based on her lack of glucose monitoring data were type 2 diabetes. Insulin sensitivity is ketones at presentation, “low” present- well ordered but revealed chaotic fluc- spared, so small doses of insulin pro- ing blood glucose of 254 mg/dl, and tuations, with several readings above duce potent hypoglycemic results. age at diagnosis. 400 mg/dl in the mornings and below Though not measured in this case, the Oral agents were suggested for 100 mg/dl at midday. Her HbA1c was presence of certain specific antibodies, C.B., but her mother insisted on insulin 9.2% (normal 4.0Ð6.0 %). A serum such as islet cell antibody (ICA) or therapy. Her primary care provider was was positive. antiÐglutamic acid decarboxylase anti- concerned about this, noting that body (anti-GAD64) are common at insulin is rarely the best first-line treat- Questions diagnosis and even diagnostic when ment in patients with type 2 diabetes, 1. How certain is the diagnosis of type 2 hyperglycemia is evident. but prescribed a temporary regimen for diabetes in this patient? C.B. was lean and was aware of no her to use until her appointment with 2. What course of action is indicated in overweight relatives. She and her moth- me. At bedtime, she was told to take patients presenting with hyper- er were the only family members with 2Ð4 U of NPH, depending on her bed- glycemia when pregnancy is diag- diabetes. Although she did not present time blood glucose level, as obtained nosed? with ketones, this is a notoriously bad with home blood glucose monitoring. 3. How should C.B. be counseled as to diagnostic marker. Patients with type 2 She was also given a sliding scale for her risk of congenital anomalies if diabetes can present with ketones if lispro to be taken before eating, she decides to continue the preg- they have fasted or are seriously ill. depending on her blood glucose read- nancy? Age at diagnosis also is not a reliable ings. If her blood glucose value was 4. What methods should be used to marker for either disease, since both <150 mg/dl, she was instructed to take screen for pregnancy in women with types of diabetes can occur in young or no supplemental lispro. diabetes? older people. Although she had not

22 Volume 19, Number 1, 2001 • CLINICAL DIABETES CASE STUDIES

University of Washington Medical Center 1989-94 (N = 192) nant. This should be a part of the 40% interview every time she visits your 35% office. 30% % Spontaneous 3. All women with diabetes who are of 25% % Birth Defects reproductive age should be counseled 20% before they are pregnant about the 15% need to optimize metabolic control and plan pregnancy and the risks of 10% spontaneous abortion and birth 5% defects associated with poor metabol- 0% ic control. 4. In diabetes, the risks of spontaneous <6% >10% abortion and fetal anomalies are 6.0 to 6.9%7.0 to 7.9%8.0 to 8.9%9.0 to 9.9% directly related to metabolic control Standardized HbA1c at First Prenatal Visit at the time of conception as well as

Figure 1. Preliminary data showing a relationship between presenting HbA1c and rate of throughout the pregnancy. Hyper- spontaneous abortion and birth defects in pregnant women with diabetes. Printed with glycemia is most destructive to fetal permission of the investigators. development during the first trimester of gestation. experienced weight loss, her extreme and is an important, and sensitivity to insulin did not suggest sometimes grave, necessity. Women REFERENCES type 2 diabetes. Finally, presenting who have had poor preconception con- serum glucose is not always a meaning- trol of their diabetes are at greater risk 1Hansen JR, Fulop MJ, Hunter MK: ful diagnostic test to assist clinicians in of spontaneous miscarriage, and those Type 2 diabetes mellitus in youth: a grow- with sustained hyperglycemia during ing challenge. Clinical Diabetes, 18:52Ð56, distinguishing between type 1 and type 2000 2 diabetes. the first trimester have a higher rate of 2American Diabetes Association: C.B.’s primary care physician did major malformations.3,4 Brown et al.5 at Report of the Expert Committee on the not know about her plans to conceive a the University of Washington Medical Diagnosis and Classification of Diabetes child. The notion that insulin is not usu- Center have observed specific risk rela- Mellitus (Committee Report). Diabetes Care 23 (Suppl 1):S4ÐS19, 2000 tionships between presenting HbA 3 ally the best first therapeutic choice in 1c Mimouni F, Tsang RC: Pregnancy out- type 2 diabetes is correct in most cases. level and the risk of poor outcomes. come in insulin-dependent diabetes: tempo- However, none of the available oral Their preliminary unpublished data, ral relationships with metabolic control dur- agents is currently approved for use in presented in Fig. 1 with permission of ing specific pregnancy periods. Am J Perinatol 5:334Ð38, 1988 pregnancy, so insulin was the only the investigators, graphically illustrate 4 the profound effect of hyperglycemia at Kitzmiller JL, Buchanan TA, Kjos S, option here. Combs CA, Ratner RE: Preconception care When pregnancy is diagnosed dur- the time of conception. for diabetes, congenital malformations, and ing a period of overt hyperglycemia, spontaneous (Technical Review). hospitalization for rapid metabolic cor- Clinical Pearls Diabetes Care 17:1502Ð1513, 1996 5 rection is suggested to reduce the rate 1. Obesity and family history of type 2 Brown Z, Gabe S, Holing E: Elevated diabetes are present in virtually all glycated hemoglobin at first prenatal visit of spontaneous abortion and fetal predicts increased birth defects and SABs: anomalies. Hospitalization is, therefore, patients with the disease. They are preliminary data from an ongoing study. strongly recommended for all women strong markers. Age, the presence of Department of and Gynecology, who present with hyperglycemia at ketones at diagnosis, and presenting University of Washington Medical Center, diagnosis of pregnancy. Our patient serum glucose are poor indicators. April 2000 was advised to proceed immediately to 2. Every woman with diabetes who is of Christian D. Herter, MD, CDE, is in the regional prenatal center, where she reproductive age must be counseled private practice in Seattle, Wash. He was promptly admitted. about contraception and family plan- also functions as a satellite preceptor Counseling expectant mothers ning and asked if there is even the for the Mayo Medical School in about the risks of fetal malformations slightest chance she could be preg- Rochester, Minn.

CLINICAL DIABETES • Volume 19, Number 1, 2001 23 CASE STUDIES

Case Study: A 36-Year-Old Woman With Type 2

Diane M. Karl, MD

Presentation continued insulin on her own and is already poorly controlled on maximal C.M. is a 36-year-old Spanish-speaking resumed taking glyburide 10 mg twice sulfonylurea treatment suggests a longer Mexican-American woman with a 3- daily. duration of diabetes. This supports the year history of type 2 diabetes. She possibility that her poor obstetrical his- was seen in her primary physician’s Questions tory may have been related to undiag- office because of a missed menstrual 1. Is there a relationship between nosed (and, therefore, uncontrolled) dia- period; a pregnancy test was positive. C.M.’s diabetes and her adverse betes. Certainly during her most recent Her past obstetrical history included obstetrical history? pregnancy, C.M. was poorly controlled five vaginal deliveries and six miscar- 2. What should have been done before during the critical period of organ devel- riages. All of her previous her recent pregnancy to increase the opment, possibly leading to an anomaly occurred before the diagnosis of dia- odds of a favorable outcome? incompatible with fetal viability. betes. Her previous medical care was in 3. What considerations affect the choice Comprehensive preconception Mexico. She was never told of any glu- of therapy for her diabetes now? counseling is now indicated for C.M. cose problem during her pregnancies, Oral diabetic medications have not been and she does not know the birth Commentary adequately studied for safety during weights of her children. At the time of In the past, most diabetic women who pregnancy. Therefore, a woman who is referral, she was 8 weeks pregnant and conceived had type 1 diabetes. Today, taking oral medication and who wishes taking glyburide 10 mg twice daily. She however, we see an increasing number to conceive should be switched to was checking her blood glucose once of women who have preconception type insulin, and control should be estab- daily in the morning with typical read- 2 diabetes. One reason is the tendency lished before she becomes pregnant. If ings between 180 and 220 mg/dl on a for many women to delay pregnancy C.M. plans another pregnancy or if she plasma-referenced meter. Family histo- until a later age. Another important fac- is not actively using , she ry was positive for diabetes in her tor, however, is the increasing number needs to resume insulin treatment. mother. of children and young adults, especially Even patients whose diabetes is well Her height was 62 inches, and her in minority groups, who are developing controlled with diet and exercise are weight was 198 lb. Other than mild type 2 diabetes.1 almost certain to require insulin during acanthosis nigricans and obesity, her The presence of diabetes in a the later stages of gestation, when physical examination was normal. She woman of childbearing years is a spe- insulin resistance increases markedly. had no retinopathy and no evidence of cial challenge. Blood glucose control Preparing patients for this likelihood neuropathy. Her glycosylated hemoglo- during the first 2 months of pregnancy and teaching insulin administration as bin (HbA1c) level was 10.5% (normal is critical to normal organ development. part of preconception counseling is <6.0%), and an office capillary blood Commonly, however, women do not advisable. Before pregnancy occurs is glucose 4 h after lunch was 201 mg/dl. seek medical attention until after this the ideal time to address any patient She was started on insulin immedi- period of early fetal development. Many fears and misconceptions about insulin ately and her glyburide was discontin- women do not yet realize they are preg- treatment. ued. She began monitoring her glucose nant during this important period, espe- For a woman of childbearing age before and after each meal, making dai- cially if the pregnancy is not planned, who does not wish to become pregnant, ly adjustments in insulin. She received which is the situation in well over half choice of therapy can be important. nutrition education with an appropriate of all pregnancies. For this reason, pre- Insulin resistance, almost universally calorie intake plus an emphasis on fre- conception counseling must be an present in type 2 diabetes, may be asso- quent smaller meals and limited carbo- important aspect of management in all ciated with decreased . This is hydrate intake. Within 1 week, her plas- diabetic women of childbearing years, most clearly evident in polycystic ma glucose values were in the target regardless of whether there is an syndrome.4 Oral diabetic medications range for pregnancy, but in the follow- expressed desire to conceive.2,3 that reduce insulin resistance, such as ing week she had a spontaneous mis- Even though C.M.’s diabetes was metformin and thiazolidinediones,5 may carriage. After her miscarriage, she dis- diagnosed 3 years ago, the fact that she also restore fertility. Thus, a previously

24 Volume 19, Number 1, 2001 • CLINICAL DIABETES CASE STUDIES

infertile patient with type 2 diabetes oral medications may be in their 3Kitzmiller JL, Buchanan TA, Kjos S, may become unexpectedly pregnant childbearing years. There are not Combs CA, Ratner R: Preconception care after starting an insulin-sensitizing med- adequate safety data to recommend of diabetes, congenital malformations, and ication unless she is counseled regard- the use of oral diabetic medications spontaneous abortions (Technical Review). ing the need for birth control. during pregnancy. Diabetes Care 19:514Ð541, 1996 4Utiger RD: Insulin and the polycystic 3. Oral diabetic medications that ovary syndrome. N Engl J Med Clinical Pearls reduce insulin resistance may 1. Preconception counseling is impor- 335:657Ð658, 1996 increase fertility in women previous- 5 tant for all women with diabetes, Dunaif A, Scott D, Finegood D, ly unable to conceive. Quintana B, Whitcomb R: The insulin sen- type 1 or type 2, who are in their sitizing agent troglitazone improves meta- childbearing years, since many REFERENCES bolic and reproductive abnormalities in the pregnancies are not planned and polycystic ovary syndrome. J Clin poor glucose control early in preg- 1Rosenbloom AL, Joe JR, Young RS, Endocrinol Metab 81:3299Ð3306, 1996 nancy is associated with a higher Winter RS: Emerging epidemic of type 2 incidence of major congenital diabetes in youth. Diabetes Care Diane M. Karl, MD, is medical director defects. 22:345Ð354, 1999 of diabetes services at Adventist Health 2American Diabetes Association: 2. Especially in minority populations, Preconception care of women with diabetes and an assistant professor of clinical increasing numbers of women with ( Statement). Diabetes Care 23 medicine at Oregon Health Sciences type 2 diabetes who are treated with (Suppl 1):S65Ð68, 2000 University in Portland, Ore.

Case Study: Complicated Results in Emergency Delivery

Ginny Lewis, ARNP, FNP, CDE

Presentation She presented to her primary care was significant for Crohn’s disease A.R. is a 33-year-old caucasian woman provider 3 days after the HbA1c was diagnosed in 1998 with no reoccur- initially diagnosed with diabetes during drawn for ongoing evaluation of hyper- rence until this hospitalization. Her pre- a recent pregnancy. The routine glu- glycemia. At that time, she was symp- pregnancy weight was 114Ð120 lb. She cose challenge test performed between tomatic for diabetic ketoacidosis. She had gained 25 lb during her pregnancy 28 and 29 weeks gestation was elevat- was hospitalized and started on an and lost 23 lb just before diagnosis. ed at 662 mg/dl. A random glucose insulin drip. A.R.’s blood glucose levels completed 1Ð2 days later was also ele- A.R.’s hospitalization was further improved postpartum, and the insulin vated at 500 mg/dl. A follow-up HbA1c complicated with gram-negative , drip was gradually discontinued. She was elevated at 11.6%. Additional adult respiratory distress syndrome, and was discharged on no medications. symptoms included a 23-lb weight loss Crohn’s disease with a new rectovagi- At her 2-week postpartum visit, over the past 3Ð4 weeks with ongoing nal fistula. She was intubated as her home blood glucose monitoring indi- “flu-like” symptoms, including fatigue, respiratory status continued to decline cated that values were ranging from 72 nausea, polyuria, and polydypsia. and was transferred to a tertiary med- to 328 mg/dl, with the majority of val- A.R. had contacted her obstetri- ical center for ongoing management. ues in the 200Ð300 mg/dl range. A cian’s office when her symptoms first She required an emergency Caesarian repeat HbA1c was 8.7%. She was appeared and was told to contact her section at 30 1/7 weeks gestation due to restarted on insulin. primary care provider for the “flu” increased . symptoms. She had called a nurse A.R. had no family history of dia- Questions triage line several times over the previ- betes with the exception of one sister 1. What is the differential diagnosis of ous 2Ð3 weeks with ongoing symptoms who had been diagnosed with gesta- gestational diabetes versus type 1 and was told to rest and take fluids. tional diabetes. Her medical history diabetes?

CLINICAL DIABETES • Volume 19, Number 1, 2001 25 CASE STUDIES

2. At what point during pregnancy adequate as monotherapy. Treatment her glucose challenge with follow-up should insulin therapy be instituted for gestational diabetes includes the use through the primary care office. It for blood glucose control? of insulin if fasting blood glucose lev- seems that if all of these providers had 3. How can communication systems be els are >95 mg/dl (5.3 mmol/l) or 2-h the full information about this case, the changed to provide for integration of postprandial values are >120 mg/dl (6.7 diagnosis could have been made more information between multiple mmol/l).1 easily, and insulin could have been ini- providers? Several days passed from the time tiated more quickly. of A.R.’s initial elevated blood glucose Commentary value and the initiation of insulin therapy. Clinical Pearls Gestational diabetes is defined as “any While HbA1c values cannot be used for 1. Hyperglycemia diagnosed during degree of carbohydrate intolerance diagnostic purposes, in this case they pregnancy is considered to be gesta- with onset first recognized during preg- further confirmed the significant degree tional diabetes until it is reclassified nancy. This definition applies whether of hyperglycemia. in the postpartum period. Immune- insulin … is used for treatment and Plasma blood glucose values initial- mediated diabetes can cause mild whether or not the condition persists ly improved in the immediate postpar- hyperglycemia that is intensified with after pregnancy.”1 Risk assessment is tum period. A.R. was sent home with- the increased counterregulatory hor- done early in the pregnancy, with aver- out medications but instructed to mone response during pregnancy. age-risk women being tested at 24Ð28 continue home glucose monitoring. 2. Insulin therapy needs to be instituted weeks’ gestation and low-risk women At her 2-week postpartum visit, quickly for cases in which MNT requiring no additional testing.1,2 A.R. whole blood glucose values were again alone is inadequate. met the criteria for average risk based indicating progressive hyperglycemia, 3. The GCT is an appropriate screening on age and a first-degree family mem- and insulin was restarted. A.R.’s post- test for an average-risk woman with ber with a history of gestational dia- partum weight was 104 lb—well below no symptoms of diabetes. In the face betes. her usual pre-pregnancy weight of of classic symptoms of diabetes, a Screening criteria for diagnosing 114Ð120 lb. Based on her ethnic back- casual plasma glucose test can elimi- diabetes include 1) symptoms of dia- ground, weight loss, abrupt presenta- nate the need for the glucose chal- betes plus casual plasma glucose >200 tion with classic diabetes symptoms, lenge. mg/dl (11.1 mmol/l), or 2) fasting plas- and limited family history, she was 4. As part of the health care industry, ma glucose >126 mg/dl (7.0 mmol/l), reclassified as having type 1 diabetes. we need to continue to work on infor- or 3) 2-h plasma glucose >200 mg/dl In immune-mediated, or type 1, dia- mation systems to track patient data (11.1 mmol/l) during an oral glucose betes, -cell destruction can be vari- and share data among multiple tolerance test (OGTT).3 For women able, with a slower destruction some- providers. Patients can become lost in who do not meet the first two criteria, a times seen in adults.3 Presentation of an ever-expanding system that relies glucose challenge test (GCT) measur- type 1 diabetes can also vary with mod- on “protocols” and does not always ing a 1-h plasma glucose following a est fasting hyperglycemia that can allow for individual differences or for 50-g oral glucose load is acceptable. quickly change to severe hyper- cases with unusual presentation. For those women who fail the initial glycemia and/or ketoacidosis in the screen, practitioners can then proceed presence of infection or other stress.3 REFERENCES with the OGTT.1 A.R. may have had mild hyperglycemia 1Coustan DR, Carpenter MW: The In A.R.’s case, she most likely pre-pregnancy that increased in severity diagnosis of gestational diabetes. Diabetes would have met the first criterion if a as the pregnancy progressed. Care 21 (Suppl. 2):B5ÐB8, 1998 2American Diabetes Association: casual blood glucose had been meas- The final issue is communication Gestational diabetes mellitus (Position ured. She had classic symptoms with among multiple health care providers. Statement). Diabetes Care 23 (Suppl. 1): weight loss, fatigue, polyuria, and poly- A.R. was part of a system that uses pri- S77ÐS79, 2000 3 dypsia. Her 1-h plasma glucose follow- mary care providers, specialists, and Expert Committee on the Diagnosis ing the glucose challenge was >600 triage nurses. She accessed all of these and Classification of Diabetes Mellitus: Report of the expert committee on the diag- mg/dl, which suggests that her casual providers as instructed. However, the nosis and classification of diabetes mellitus. glucose would also have been quite information did not seem to be clearly Diabetes Care 23 (Suppl. 1):S4ÐS19, 2000 high. communicated among these different Medical nutrition therapy (MNT) is types of providers. A.R. called triage Ginny Lewis, ARNP, FNP, CDE, is a certainly a major part of diabetes man- nurses several times with her concerns nurse practitioner at the Diabetes Care agement. However, with this degree of of increased fatigue, nausea, and Center of the University of Washington hyperglycemia, MNT would not be weight loss. The specialist performed School of Medicine in Seattle.

26 Volume 19, Number 1, 2001 • CLINICAL DIABETES