diabetes case study quizlet

An official website of the United States government

The .gov means it’s official. Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

The site is secure. The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

• Publications
• Account settings

Preview improvements coming to the PMC website in October 2024. Learn More or Try it out now .

• Advanced Search
• Journal List
• HHS Author Manuscripts

Case 6–2020: A 34-Year-Old Woman with Hyperglycemia

Presentation of case.

Dr. Max C. Petersen (Medicine): A 34-year-old woman was evaluated in the diabetes clinic of this hospital for hyperglycemia.

Eleven years before this presentation, the blood glucose level was 126 mg per deciliter (7.0 mmol per liter) on routine laboratory evaluation, which was performed as part of an annual well visit. The patient could not recall whether she had been fasting at the time the test had been performed. One year later, the fasting blood glucose level was 112 mg per deciliter (6.2 mmol per liter; reference range, <100 mg per deciliter [<5.6 mmol per liter]).

Nine years before this presentation, a randomly obtained blood glucose level was 217 mg per deciliter (12.0 mmol per liter), and the patient reported polyuria. At that time, the glycated hemoglobin level was 5.8% (reference range, 4.3 to 5.6); the hemoglobin level was normal. One year later, the glycated hemoglobin level was 5.9%. The height was 165.1 cm, the weight 72.6 kg, and the body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) 26.6. The patient received a diagnosis of prediabetes and was referred to a nutritionist. She made changes to her diet and lost 4.5 kg of body weight over a 6-month period; the glycated hemoglobin level was 5.5%.

Six years before this presentation, the patient became pregnant with her first child. Her prepregnancy BMI was 24.5. At 26 weeks of gestation, the result of a 1-hour oral glucose challenge test (i.e., the blood glucose level obtained 1 hour after the oral administration of a 50-g glucose load in the nonfasting state) was 186 mg per deciliter (10.3 mmol per liter; reference range, <140 mg per deciliter [<7.8 mmol per liter]). She declined a 3-hour oral glucose tolerance test; a presumptive diagnosis of gestational diabetes was made. She was asked to follow a meal plan for gestational diabetes and was treated with insulin during the pregnancy. Serial ultrasound examinations for fetal growth and monitoring were performed. At 34 weeks of gestation, the fetal abdominal circumference was in the 76th percentile for gestational age. Polyhydramnios developed at 37 weeks of gestation. The child was born at 39 weeks 3 days of gestation, weighed 3.9 kg at birth, and had hypoglycemia after birth, which subsequently resolved. Six weeks post partum, the patient’s fasting blood glucose level was 120 mg per deciliter (6.7 mmol per liter), and the result of a 2-hour oral glucose tolerance test (i.e., the blood glucose level obtained 2 hours after the oral administration of a 75-g glucose load in the fasting state) was 131 mg per deciliter (7.3 mmol per liter; reference range, <140 mg per deciliter). Three months post partum, the glycated hemoglobin level was 6.1%. Lifestyle modification for diabetes prevention was recommended.

Four and a half years before this presentation, the patient became pregnant with her second child. Her prepregnancy BMI was 25.1. At 5 weeks of gestation, she had an elevated blood glucose level. Insulin therapy was started at 6 weeks of gestation, and episodes of hypoglycemia occurred during the pregnancy. Serial ultrasound examinations for fetal growth and monitoring were performed. At 28 weeks of gestation, the fetal abdominal circumference was in the 35th percentile for gestational age, and the amniotic fluid level was normal. Labor was induced at 38 weeks of gestation; the child weighed 2.6 kg at birth. Neonatal blood glucose levels were reported as stable after birth. Six weeks post partum, the patient’s fasting blood glucose level was 133 mg per deciliter (7.4 mmol per liter), and the result of a 2-hour oral glucose tolerance test was 236 mg per deciliter (13.1 mmol per liter). The patient received a diagnosis of type 2 diabetes mellitus; lifestyle modification was recommended. Three months post partum, the glycated hemoglobin level was 5.9% and the BMI was 30.0. Over the next 2 years, she followed a low-carbohydrate diet and regular exercise plan and self-monitored the blood glucose level.

Two years before this presentation, the patient became pregnant with her third child. Blood glucose levels were again elevated, and insulin therapy was started early in gestation. She had episodes of hypoglycemia that led to adjustment of her insulin regimen. The child was born at 38 weeks 5 days of gestation, weighed 3.0 kg at birth, and had hypoglycemia that resolved 48 hours after birth. After the birth of her third child, the patient started to receive metformin, which had no effect on the glycated hemoglobin level, despite adjustment of the therapy to the maximal dose.

One year before this presentation, the patient became pregnant with her fourth child. Insulin therapy was again started early in gestation. The patient reported that episodes of hypoglycemia occurred. Polyhydramnios developed. The child was born at 38 weeks 6 days of gestation and weighed 3.5 kg. The patient sought care at the diabetes clinic of this hospital for clarification of her diagnosis.

The patient reported following a low-carbohydrate diet and exercising 5 days per week. There was no fatigue, change in appetite, change in vision, chest pain, shortness of breath, polydipsia, or polyuria. There was no history of anemia, pancreatitis, hirsutism, proximal muscle weakness, easy bruising, headache, sweating, tachycardia, gallstones, or diarrhea. Her menstrual periods were normal. She had not noticed any changes in her facial features or the size of her hands or feet.

The patient had a history of acne and low-back pain. Her only medication was metformin. She had no known medication allergies. She lived with her husband and four children in a suburban community in New England and worked as an administrator. She did not smoke tobacco or use illicit drugs, and she rarely drank alcohol. She identified as non-Hispanic white. Both of her grandmothers had type 2 diabetes mellitus. Her father had hypertension, was overweight, and had received a diagnosis of type 2 diabetes at 50 years of age. Her mother was not overweight and had received a diagnosis of type 2 diabetes at 48 years of age. The patient had two sisters, neither of whom had a history of diabetes or gestational diabetes. There was no family history of hemochromatosis.

On examination, the patient appeared well. The blood pressure was 126/76 mm Hg, and the heart rate 76 beats per minute. The BMI was 25.4. The physical examination was normal. The glycated hemoglobin level was 6.2%.

A diagnostic test was performed.

DIFFERENTIAL DIAGNOSIS

Dr. Miriam S. Udler: I am aware of the diagnosis in this case and participated in the care of this patient. This healthy 34-year-old woman, who had a BMI just above the upper limit of the normal range, presented with a history of hyperglycemia of varying degrees since 24 years of age. When she was not pregnant, she was treated with lifestyle measures as well as metformin therapy for a short period, and she maintained a well-controlled blood glucose level. In thinking about this case, it is helpful to characterize the extent of the hyperglycemia and then to consider its possible causes.

CHARACTERIZING HYPERGLYCEMIA

This patient’s hyperglycemia reached a threshold that was diagnostic of diabetes 1 on two occasions: when she was 25 years of age, she had a randomly obtained blood glucose level of 217 mg per deciliter with polyuria (with diabetes defined as a level of ≥200 mg per deciliter [≥11.1 mmol per liter] with symptoms), and when she was 30 years of age, she had on the same encounter a fasting blood glucose level of 133 mg per deciliter (with diabetes defined as a level of ≥126 mg per deciliter) and a result on a 2-hour oral glucose tolerance test of 236 mg per deciliter (with diabetes defined as a level of ≥200 mg per deciliter). On both of these occasions, her glycated hemoglobin level was in the prediabetes range (defined as 5.7 to 6.4%). In establishing the diagnosis of diabetes, the various blood glucose studies and glycated hemoglobin testing may provide discordant information because the tests have different sensitivities for this diagnosis, with glycated hemoglobin testing being the least sensitive. 2 Also, there are situations in which the glycated hemoglobin level can be inaccurate; for example, the patient may have recently received a blood transfusion or may have a condition that alters the life span of red cells, such as anemia, hemoglobinopathy, or pregnancy. 3 These conditions were not present in this patient at the time that the glycated hemoglobin measurements were obtained. In addition, since the glycated hemoglobin level reflects the average glucose level typically over a 3-month period, discordance with timed blood glucose measurements can occur if there has been a recent change in glycemic control. This patient had long-standing mild hyperglycemia but met criteria for diabetes on the basis of the blood glucose levels noted.

Type 1 and Type 2 Diabetes

Now that we have characterized the patient’s hyperglycemia as meeting criteria for diabetes, it is important to consider the possible types. More than 90% of adults with diabetes have type 2 diabetes, which is due to progressive loss of insulin secretion by beta cells that frequently occurs in the context of insulin resistance. This patient had received a diagnosis of type 2 diabetes; however, some patients with diabetes may be given a diagnosis of type 2 diabetes on the basis of not having features of type 1 diabetes, which is characterized by autoimmune destruction of the pancreatic beta cells that leads to rapid development of insulin dependence, with ketoacidosis often present at diagnosis.

Type 1 diabetes accounts for approximately 6% of all cases of diabetes in adults (≥18 years of age) in the United States, 4 and 80% of these cases are diagnosed before the patient is 20 years of age. 5 Since this patient’s diabetes was essentially nonprogressive over a period of at least 9 years, she most likely does not have type 1 diabetes. It is therefore not surprising that she had received a diagnosis of type 2 diabetes, but there are several other types of diabetes to consider, particularly since some features of her case do not fit with a typical case of type 2 diabetes, such as her age at diagnosis, the presence of hyperglycemia despite a nearly normal BMI, and the mild and nonprogressive nature of her disease over the course of many years.

Less Common Types of Diabetes

Latent autoimmune diabetes in adults (LADA) is a mild form of autoimmune diabetes that should be considered in this patient. However, there is controversy as to whether LADA truly represents an entity that is distinct from type 1 diabetes. 6 Both patients with type 1 diabetes and patients with LADA commonly have elevated levels of diabetes-associated autoantibodies; however, LADA has been defined by an older age at onset (typically >25 years) and slower progression to insulin dependence (over a period of >6 months). 7 This patient had not been tested for diabetes-associated autoantibodies. I ordered these tests to help evaluate for LADA, but this was not my leading diagnosis because of her young age at diagnosis and nonprogressive clinical course over a period of at least 9 years.

If the patient’s diabetes had been confined to pregnancy, we might consider gestational diabetes, but she had hyperglycemia outside of pregnancy. Several medications can cause hyperglycemia, including glucocorticoids, atypical antipsychotic agents, cancer immunotherapies, and some antiretroviral therapies and immunosuppressive agents used in transplantation. 8 However, this patient was not receiving any of these medications. Another cause of diabetes to consider is destruction of the pancreas due to, for example, cystic fibrosis, a tumor, or pancreatitis, but none of these were present. Secondary endocrine disorders — including excess cortisol production, excess growth hormone production, and pheochromocytoma — were considered to be unlikely in this patient on the basis of the history, review of symptoms, and physical examination.

Monogenic Diabetes

A final category to consider is monogenic diabetes, which is caused by alteration of a single gene. Types of monogenic diabetes include maturity-onset diabetes of the young (MODY), neonatal diabetes, and syndromic forms of diabetes. Monogenic diabetes accounts for 1 to 6% of cases of diabetes in children 9 and approximately 0.4% of cases in adults. 10 Neonatal diabetes is diagnosed typically within the first 6 months of life; syndromic forms of monogenic diabetes have other abnormal features, including particular organ dysfunction. Neither condition is applicable to this patient.

MODY is an autosomal dominant condition characterized by primary pancreatic beta-cell dysfunction that causes mild diabetes that is diagnosed during adolescence or early adulthood. As early as 1964, the nomenclature “maturity-onset diabetes of the young” was used to describe cases that resembled adult-onset type 2 diabetes in terms of the slow progression to insulin use (as compared with the rapid progression in type 1 diabetes) but occurred in relatively young patients. 11 Several genes cause distinct forms of MODY that have specific disease features that inform treatment, and thus MODY is a clinically important diagnosis. Most forms of MODY cause isolated abnormal glucose levels (in contrast to syndromic monogenic diabetes), a manifestation that has contributed to its frequent misdiagnosis as type 1 or type 2 diabetes. 12

Genetic Basis of MODY

Although at least 13 genes have been associated with MODY, 3 genes — GCK , which encodes glucokinase, and HNF1A and HNF4A , which encode hepatocyte nuclear factors 1A and 4A, respectively — account for most cases. MODY associated with GCK (known as GCK-MODY) is characterized by mild, nonprogressive hyperglycemia that is present since birth, whereas the forms of MODY associated with HNF1A and HNF4A (known as HNF1A-MODY and HNF4A-MODY, respectively) are characterized by the development of diabetes, typically in the early teen years or young adulthood, that is initially mild and then progresses such that affected patients may receive insulin before diagnosis.

In patients with GCK-MODY, genetic variants reduce the function of glucokinase, the enzyme in pancreatic beta cells that functions as a glucose sensor and controls the rate of entry of glucose into the glycolytic pathway. As a result, reduced sensitivity to glucose-induced insulin secretion causes asymptomatic mild fasting hyperglycemia, with an upward shift in the normal range of the fasting blood glucose level to 100 to 145 mg per deciliter (5.6 to 8.0 mmol per liter), and also causes an upward shift in postprandial blood glucose levels, but with tight regulation maintained ( Fig. 1 ). 13 This mild hyperglycemia is not thought to confer a predisposition to complications of diabetes, 14 is largely unaltered by treatment, 15 and does not necessitate treatment outside of pregnancy.

Key features suggesting maturity-onset diabetes of the young (MODY) in this patient were an age of less than 35 years at the diagnosis of diabetes, a strong family history of diabetes with an autosomal dominant pattern of inheritance, and hyperglycemia despite a close-to-normal body-mass index. None of these features is an absolute criterion. MODY is caused by single gene–mediated disruption of pancreatic beta-cell function. In MODY associated with the GCK gene (known as GCK-MODY), disrupted glucokinase function causes a mild upward shift in glucose levels through-out the day and does not necessitate treatment. 13 In the pedigree, circles represent female family members, squares male family members, blue family members affected by diabetes, and green unaffected family members. The arrow indicates the patient.

In contrast to GCK-MODY, the disorders HNF1A-MODY and HNF4A-MODY result in progressive hyperglycemia that eventually leads to treatment. 16 Initially, there may be a normal fasting glucose level and large spikes in postprandial glucose levels (to >80 mg per deciliter [>4.4 mmol per liter]). 17 Patients can often be treated with oral agents and discontinue insulin therapy started before the diagnosis of MODY. 18 Of note, patients with HNF1A-MODY or HNF4A-MODY are typically sensitive to treatment with sulfonylureas 19 but may also respond to glucagon-like peptide-1 receptor agonists. 20

This patient had received a diagnosis of diabetes before 35 years of age, had a family history of diabetes involving multiple generations, and was not obese. These features are suggestive of MODY but do not represent absolute criteria for the condition ( Fig. 1 ). 1 Negative testing for diabetes-associated autoantibodies would further increase the likelihood of MODY. There are methods to calculate a patient’s risk of having MODY associated with GCK , HNF1A , or HNF4A . 21 , 22 Using an online calculator ( www.diabetesgenes.org/mody-probability-calculator ), we estimate that the probability of this patient having MODY is at least 75.5%. Genetic testing would be needed to confirm this diagnosis, and in patients at an increased risk for MODY, multigene panel testing has been shown to be cost-effective. 23 , 24

DR. MIRIAM S. UDLER’S DIAGNOSIS

Maturity-onset diabetes of the young, most likely due to a GCK variant.

DIAGNOSTIC TESTING

Dr. Christina A. Austin-Tse: A diagnostic sequencing test of five genes associated with MODY was performed. One clinically significant variant was identified in the GCK gene ( {"type":"entrez-nucleotide","attrs":{"text":"NM_000162.3","term_id":"167621407","term_text":"NM_000162.3"}} NM_000162.3 ): a c.787T→C transition resulting in the p.Ser263Pro missense change. Review of the literature and variant databases revealed that this variant had been previously identified in at least three patients with early-onset diabetes and had segregated with disease in at least three affected members of two families (GeneDx: personal communication). 25 , 26 Furthermore, the variant was rare in large population databases (occurring in 1 out of 128,844 European chromosomes in gnomAD 27 ), a feature consistent with a disease-causing role. Although the serine residue at position 263 was not highly conserved, multiple in vitro functional studies have shown that the p.Ser263Pro variant negatively affects the stability of the glucokinase enzyme. 26 , 28 – 30 As a result, this variant met criteria to be classified as “likely pathogenic.” 31 As mentioned previously, a diagnosis of GCK-MODY is consistent with this patient’s clinical features. On subsequent testing of additional family members, the same “likely pathogenic” variant was identified in the patient’s father and second child, both of whom had documented hyperglycemia.

DISCUSSION OF MANAGEMENT

Dr. Udler: In this patient, the diagnosis of GCK-MODY means that it is normal for her blood glucose level to be mildly elevated. She can stop taking metformin because discontinuation is not expected to substantially alter her glycated hemoglobin level 15 , 32 and because she is not at risk for complications of diabetes. 14 However, she should continue to maintain a healthy lifestyle. Although patients with GCK-MODY are not typically treated for hyperglycemia outside of pregnancy, they may need to be treated during pregnancy.

It is possible for a patient to have type 1 or type 2 diabetes in addition to MODY, so this patient should be screened for diabetes according to recommendations for the general population (e.g., in the event that she has a risk factor for diabetes, such as obesity). 1 Since the mild hyperglycemia associated with GCK-MODY is asymptomatic (and probably unrelated to the polyuria that this patient had described in the past), the development of symptoms of hyperglycemia, such as polyuria, polydipsia, or blurry vision, should prompt additional evaluation. In patients with GCK-MODY, the glycated hemoglobin level is typically below 7.5%, 33 so a value rising above that threshold or a sudden large increase in the glycated hemoglobin level could indicate concomitant diabetes from another cause, which would need to be evaluated and treated.

This patient’s family members are at risk for having the same GCK variant, with a 50% chance of offspring inheriting a variant from an affected parent. Since the hyperglycemia associated with GCK-MODY is present from birth, it is necessary to perform genetic testing only in family members with demonstrated hyperglycemia. I offered site-specific genetic testing to the patient’s parents and second child.

Dr. Meridale V. Baggett (Medicine): Dr. Powe, would you tell us how you would treat this patient during pregnancy?

Dr. Camille E. Powe: During the patient’s first pregnancy, routine screening led to a presumptive diagnosis of gestational diabetes, the most common cause of hyperglycemia in pregnancy. Hyperglycemia in pregnancy is associated with adverse pregnancy outcomes, 34 and treatment lowers the risk of such outcomes. 35 , 36 Two of the most common complications — fetal overgrowth (which can lead to birth injuries, shoulder dystocia, and an increased risk of cesarean delivery) and neonatal hypoglycemia — are thought to be the result of fetal hyperinsulinemia. 37 Maternal glucose is freely transported across the placenta, and excess glucose augments insulin secretion from the fetal pancreas. In fetal life, insulin is a potent growth factor, and neonates who have hyperinsulinemia in utero often continue to secrete excess insulin in the first few days of life. In the treatment of pregnant women with diabetes, we strive for strict blood sugar control (fasting blood glucose level, <95 mg per deciliter [<5.3 mmol per liter]; 2-hour postprandial blood glucose level, <120 mg per deciliter) to decrease the risk of these and other hyperglycemia-associated adverse pregnancy outcomes. 38 – 40

In the third trimester of the patient’s first pregnancy, obstetrical ultrasound examination revealed a fetal abdominal circumference in the 76th percentile for gestational age and polyhydramnios, signs of fetal exposure to maternal hyperglycemia. 40 – 42 Case series involving families with GCK-MODY have shown that the effect of maternal hyperglycemia on the fetus depends on whether the fetus inherits the pathogenic GCK variant. 43 – 48 Fetuses that do not inherit the maternal variant have overgrowth, presumably due to fetal hyperinsulinemia ( Fig. 2A ). In contrast, fetuses that inherit the variant do not have overgrowth and are born at a weight that is near the average for gestational age, despite maternal hyperglycemia, presumably because the variant results in decreased insulin secretion ( Fig. 2B ). Fetuses that inherit GCK-MODY from their fathers and have euglycemic mothers appear to be undergrown, most likely because their insulin secretion is lower than normal when they and their mothers are euglycemic ( Fig. 2D ). Because fetal overgrowth and polyhydramnios occurred during this patient’s first pregnancy and neonatal hypoglycemia developed after the birth, the patient’s first child is probably not affected by GCK-MODY.

Pathogenic variants that lead to GCK-MODY, when carried by a fetus, change the usual relationship of maternal hyperglycemia to fetal hyperinsulinemia and fetal overgrowth. GCK-MODY–affected fetuses have lower insulin secretion than unaffected fetuses in response to the same maternal blood glucose level. In a hyperglycemic mother carrying a fetus who is unaffected by GCK-MODY, excessive fetal growth is usually apparent (Panel A). Studies involving GCK-MODY–affected hyperglycemic mothers have shown that fetal growth is normal despite maternal hyperglycemia when a fetus has the maternal GCK variant (Panel B). The goal of treatment of maternal hyperglycemia when a fetus is unaffected by GCK-MODY is to establish euglycemia to normalize fetal insulin levels and growth (Panel C); whether this can be accomplished in the case of maternal GCK-MODY is controversial, given the genetically determined elevated maternal glycemic set point. In the context of maternal euglycemia, GCK-MODY–affected fetuses may be at risk for fetal growth restriction (Panel D).

In accordance with standard care for pregnant women with diabetes who do not meet glycemic targets after dietary modification, 38 , 39 the patient was treated with insulin during her pregnancies. In her second pregnancy, treatment was begun early, after hyperglycemia was detected in the first trimester. Because she had not yet received the diagnosis of GCK-MODY during any of her pregnancies, no consideration of this condition was given during her obstetrical treatment. Whether treatment affects the risk of hyperglycemia-associated adverse pregnancy outcomes in pregnant women with known GCK-MODY is controversial, with several case series showing that the birth weight percentile in unaffected neonates remains consistent regardless of whether the mother is treated with insulin. 44 , 45 Evidence suggests that it may be difficult to overcome a genetically determined glycemic set point in patients with GCK-MODY with the use of pharmacotherapy, 15 , 32 and affected patients may have symptoms of hypoglycemia when the blood glucose level is normal because of an enhanced counterregulatory response. 49 , 50 Still, to the extent that it is possible, it would be desirable to safely lower the blood glucose level in a woman with GCK-MODY who is pregnant with an unaffected fetus in order to decrease the risk of fetal overgrowth and other consequences of mildly elevated glucose levels ( Fig. 2C ). 46 , 47 , 51 In contrast, there is evidence that lowering the blood glucose level in a pregnant woman with GCK-MODY could lead to fetal growth restriction if the fetus is affected ( Fig. 2D ). 45 , 52 During this patient’s second pregnancy, she was treated with insulin beginning in the first trimester, and her daughter’s birth weight was near the 16th percentile for gestational age; this outcome is consistent with the daughter’s ultimate diagnosis of GCK-MODY.

Expert opinion suggests that, in pregnant women with GCK-MODY, insulin therapy should be deferred until fetal growth is assessed by means of ultrasound examination beginning in the late second trimester. If there is evidence of fetal overgrowth, the fetus is presumed to be unaffected by GCK-MODY and insulin therapy is initiated. 53 After I have counseled women with GCK-MODY on the potential risks and benefits of insulin treatment during pregnancy, I have sometimes used a strategy of treating hyperglycemia from early in pregnancy using modified glycemic targets that are less stringent than the targets typically used during pregnancy. This strategy attempts to balance the risk of growth restriction in an affected fetus (as well as maternal hypoglycemia) with the potential benefit of glucose-lowering therapy for an unaffected fetus.

Dr. Udler: The patient stopped taking metformin, and subsequent glycated hemoglobin levels remained unchanged, at 6.2%. Her father and 5-year-old daughter (second child) both tested positive for the same GCK variant. Her father had a BMI of 36 and a glycated hemoglobin level of 7.8%, so I counseled him that he most likely had type 2 diabetes in addition to GCK-MODY. He is currently being treated with metformin and lifestyle measures. The patient’s daughter now has a clear diagnosis to explain her hyperglycemia, which will help in preventing misdiagnosis of type 1 diabetes, given her young age, and will be important for the management of any future pregnancies. She will not need any medical follow-up for GCK-MODY until she is considering pregnancy.

FINAL DIAGNOSIS

Maturity-onset diabetes of the young due to a GCK variant.

Acknowledgments

We thank Dr. Andrew Hattersley and Dr. Sarah Bernstein for helpful comments on an earlier draft of the manuscript.

This case was presented at the Medical Case Conference.

No potential conflict of interest relevant to this article was reported.

Disclosure forms provided by the authors are available with the full text of this article at NEJM.org .

Learn how UpToDate can help you.

Select the option that best describes you

• Medical Professional
• Resident, Fellow, or Student
• Hospital or Institution
• Group Practice
• Patient or Caregiver
• Find in topic

RELATED TOPICS

The patient has been treated for hypertension for 10 years, currently with amlodipine 10 mg by mouth daily. She was once told that her cholesterol value was "borderline high" but does not know the value.

She denies symptoms of diabetes, chest pain, shortness of breath, heart disease, stroke, or circulatory problems of the lower extremities.

She estimates her current weight at 165 lbs (75 kg). She thinks she weighed 120 lbs (54 kg) at age 21 years but gained weight with each of her three pregnancies and did not return to her nonpregnant weight after each delivery. She weighed 155 lbs one year ago but gained weight following retirement from her job as an elementary school teacher. No family medical history is available because she was adopted. She does not eat breakfast, has a modest lunch, and consumes most of her calories at supper and in the evening.

On examination, blood pressure is 140/85 mmHg supine and 140/90 mmHg upright with a regular heart rate of 76 beats/minute. She weighs 169 lbs, with a body mass index (BMI) of 30.9 kg/m 2 . Fundoscopic examination reveals no evidence of retinopathy. Vibratory sensation is absent at the great toes, reduced at the medial malleoli, and normal at the tibial tubercles. Light touch sensation is reduced in the feet but intact more proximally. Knee jerks are 2+ bilaterally, but the ankle jerks are absent. The examination is otherwise within normal limits.

Ohio State nav bar

The Ohio State University

• BuckeyeLink
• Find People
• Search Ohio State

Review Questions Correct Answers

#1. Which of the following mechanisms does not lead to hyperglycemia in diabetic patients?

a. Exogenous administration of insulin b. Increased hepatic glucose production c. Decreased insulin secretion d. Decreased peripheral glucose uptake

Rationale : The correct answer is exogenous administration of insulin. Administration of insulin would increase the body’s available insulin and lead to normal or lower blood glucose levels. Increased hepatic glucose production leads to hyperglycemia because there is more glucose for insulin to uptake into the cell for excretion. Decreased insulin secretion leads to hyperglycemia because there is not enough insulin to meet the body’s needs for glucose uptake into the cell for excretion. Decreased peripheral glucose uptake leads to hyperglycemia because the glucose isn’t being pulled into the cell for excretion (McCance & Huether, 2019).

#2. Which of the following would not indicate the diagnosis of diabetes mellitus?

a. Fasting plasma glucose of 120 mg/dL b. Random plasma glucose of 250 mg/dL with symptoms of hyperglycemia c. Fasting plasma glucose of 145 mg/dL d. 2 hour plasma glucose of 220 mg/dL

Rationale : The correct answer is fasting plasma glucose of 120 mg/dL. Criteria for diagnosis of DM includes fasting plasma glucose of ≥126 mg/dL. A fasting plasma glucose of 145 mg/dL would indicate DM because it is greater than the criteria of ≥126 mg/dL. Criteria for DM for a random plasma glucose with symptoms of hyperglycemia is ≥ 200 mg/dL. Criteria for DM in a 2 hour plasma glucose is ≥ 200 mg/dL (McCance & Huether, 2019).

#3. Which of the following hemoglobin A1c laboratory values is in a normal, healthy range?

a. 7.0% b. 8.5% c. 6.8% d. 5.1%

Rationale : The correct answer is 5.1%. A person diagnosed with diabetes mellitus will have a hemoglobin A1c of ≥ 6.5%, so a hemoglobin A1c level of 5.1% is within healthy, normal limits, where as 7.0%, 8.5% and 6.8% would all indicate DM (McCance & Huether, 2019).

#4. Which of the following cell types is responsible for secreting insulin in the body in response to elevated glucose in the bloodstream?

a. Alpha pancreatic cells b. Beta pancreatic cells c. Kupffer cells d. Adipose cells

Rationale : The correct answer is beta pancreatic cells. Beta pancreatic cells are located in the islets of Langerhans in the pancreas. They are responsible for producing insulin and the insulin then takes up glucose into the cells for excretion. Kupffer cells are macrophages that are important for lipid metabolism, bilirubin production, and healing liver damage. Alpha pancreatic cells are responsible for secreting glucagon. Glucagon is the antagonist to insulin and increased blood glucose levels. Adipose cells are fat cells that produce adipokines. Increased adipokines in the blood contributes to decreased insulin production (McCance & Huether, 2019).

#5. Which activity would lead to the progression of the disease for type two diabetes?

a. Participating in regular physical activity b. Eating a balanced and healthy diet c. Closely monitoring blood sugar levels d. Adopting a sedentary lifestyle

Rationale : The correct answer is adopting a sedentary lifestyle. Having a sedentary lifestyle is a risk factor for DM. After diagnosis, if a patient maintained a sedentary lifestyle, the disease would progress. Participating in regular physical activity and eating a balanced diet are associated with weight loss. Since obesity is a major contributor to DM, decreasing body weight would slow the progression of DM. Closely monitoring blood glucose levels is associated with controlling DM and slowing the progression of the disease (McCance & Huether, 2019; Bellou, Belbasis, Tzoulaki, & Evangelos, 2018).

• Previous Article

Presentation

Clinical pearls, article information, case study: diabetic ketoacidosis in type 2 diabetes: “look under the sheets”.

• Split-Screen
• Article contents
• Figures & tables
• Supplementary Data
• Peer Review
• Open the PDF for in another window
• Cite Icon Cite
• Get Permissions

Brian J. Welch , Ivana Zib; Case Study: Diabetic Ketoacidosis in Type 2 Diabetes: “Look Under the Sheets”. Clin Diabetes 1 October 2004; 22 (4): 198–200. https://doi.org/10.2337/diaclin.22.4.198

Download citation file:

• Ris (Zotero)
• Reference Manager

Diabetic ketoacidosis (DKA) is a cardinal feature of type 1 diabetes. However, there is a strong, almost dogmatic, errant perception by physicians that DKA is a complication that only occurs in patients with type 1 diabetes. This is not true. DKA does occur in type 2 diabetes; however, it rarely occurs in the absence of a precipitating event.

R.T., a 25-year-old African-American man with type 2 diabetes presented with a 5-day history of nausea and vomiting. He also reported a 2-week history of polyuria and polydipsia and a 10-lb weight loss. A review of symptoms was pertinent for a 5-day history of persistent lower back pain.

The patient was diagnosed with type 2 diabetes 5 years ago when he presented to a different hospital with symptoms of polyuria, polydipsia, and weight loss. He was given a prescription for a sulfonylurea, which he says he took until his initial prescription ran out 1 month later. He had not taken any other medication since that time.

Physical examination revealed an afebrile, obese man (BMI 40 kg/m 2 ) with prominent acanthosis nigricans, no retinopathy by direct funduscopic exam, and a normal neurological exam, including motor function and sensation. The patient had no tenderness to palpation over the lumbrosacral spine or paraspinous muscles despite his complaint of lower back pain.

The laboratory data showed an anion gap, metabolic acidosis, and hyperglycemia (pH of 7.14, anion gap of 24, bicarbonate 6 mmol/l, urinary ketones 150 mg/dl, glucose 314 mg/dl) consistent with the diagnosis of DKA. His white blood count was 20,400/μl. Urinalysis demonstrated no evidence of infection. The patient's hemoglobin A 1c (A1C) was 13.5%.

The patient was admitted and treated aggressively with intravenous fluid and an insulin-glucose infusion. A non-contrast magnetic resonance imaging(MRI) of the lumbosacral spine (L-spine) was obtained because of the patient's persistent complaint of lower back pain. The L-spine MRI results were negative for pathology. However, R.T. reported increasing discomfort and now noted weakness and numbness in his bilateral lower extremities.

Neurology was consulted, and during their assessment, the patient became incontinent and was found to have 0/5 strength in the lower extremities,severely compromised sensation, and decreased rectal tone. A contrast MRI of both the thoracic and lumbar spine was ordered, and the patient was found to have a T10-T12 epidural abscess ( Figure 1 ).

Epidural abscess precipitating DKA in a type 2 diabetic patient.

The patient's antibiotic coverage was broadly expanded, high-dose intravenous steroids were initiated, and neurosurgery was urgently consulted. Emergent evacuation of the epidural abscess with laminectomies of T10-T12 was performed without complication.

R.T.'s neurogenic bladder resolved without further intervention. After intensive inpatient rehabilitation, he had 3/5 strength in bilateral lower extremities and was still unable to ambulate.

S.D., a 39-year-old white man with type 2 diabetes and mild mental retardation, presented with a 3-week history of polyuria and polydipsia, as well as dysuria, left hip pain, and a feeling of incomplete bladder emptying. Because of the severity of his left hip discomfort, the patient required a cane to ambulate.

The patient was diagnosed with type 2 diabetes 4 years ago on the basis of an elevated fasting blood glucose level during a routine medical examination. He was started on oral hypoglycemic agents, but he discontinued them after 1 month because he was unable to pay for them.

On physical exam, S.D. was afebrile but tachycardic (heart rate 131 bpm)and hypertensive (blood pressure 192/118 mmHg). General examination revealed a wasted, severely volume-depleted man. Thrush was observed on oropharyngeal exam. Cardiopulmonary and abdominal examinations were unremarkable. The patient had point tenderness on the anterior aspect of his left hip. Rectal examination revealed a non-tender prostate.

The laboratory data showed an anion gap, metabolic acidosis, and hyperglycemia (pH 7.24, bicarbonate 9 mmol/l, anion gap 24, urinary ketones 150 mg/dl, and glucose 322 mg/dl) consistent with the diagnosis of DKA. Urinalysis was remarkable for large blood, 4+ bacteria, and > 400 white blood cells. S.D.'s serum white blood count was 22,200, and his erythrocyte sedimentation rate was 109 mm/hour. His A1C result was 12.6%.

The patient was admitted and treated with intravenous fluids and an insulin-glucose infusion. Cultures were obtained. S.D. was started empirically on ticarcillin/clavulanic acid because of concern for left hip osteomyelitis and complicated urinary tract infection. An MRI of the left hip was ordered to evaluate for suspected osteomyelitis. Unexpectedly, it revealed left hip myonecrosis and a large loculated prostatic abscess( Figure 2 ).

Prostatic abscess precipitating DKA in a type 2 diabetic patient.

Urology was consulted, and the patient underwent transurethral drainage of the prostatic abscess. Methicillin-sensitive Staphylococcus aureus grew from both blood and urine cultures. S.D. was treated with intravenous antibiotics per culture sensitivities. The myonecrosis was treated conservatively.

The patient recovered well. He was started on subcutaneous insulin and discharged home to complete a 2-week course of intravenous antibiotics.

What is the mechanism of DKA?

Why does DKA occur in type 2 diabetes?

DKA is a cardinal feature of type 1 diabetes, which has led to the widespread errant perception that it is a complication unique to type 1 diabetes. However, it has been repeatedly reported that DKA does occur in patients with type 2 diabetes. 1 - 5   Moreover, as the cases presented here illustrate, it can occur even in patients who were previously insulinindependent.

A recent study evaluating 138 consecutive admissions for DKA at a large academic center observed that 21.7% had type 2 diabetes. 6   Nearly 70% of the admissions involved discontinuation of medications, and almost half had an identifiable infection when an intensive search was undertaken.

A review of the mechanism of DKA is important. Ketoacidosis occurs as a function not only of severe insulin deficiency, but also of elevated glucagon levels. Insulin is an anabolic hormone. Severe insulin deficiency results in decreased glucose utilization by muscle and an unregulated increase in lipolysis. This leads to an enhanced delivery of gluconeogenetic precursors(glycerol and alanine) to the liver. Furthermore, removal of the normal suppressive effect of insulin causes glucagon elevation. 7 , 8   Glucagon is a catabolic hormone. Glucagon promotes gluconeogenesis, decreases oxidation of free fatty acids to triglycerides, and promotes hepatic ketogenesis. 9  

Importantly, the concentration of insulin required to suppress lipolysis is only one-tenth of that required to promote glucose utilization. 10   Typically, moderate insulin deficiency (as observed in patients with type 2 diabetes) is associated with sufficient insulin to block lipolysis (and therefore ketoacid formation), but not enough to promote glucose utilization. This leads to hyperglycemia without formation of the ketoacids.

When DKA occurs in patients with type 2 diabetes, the presumed mechanism of ketoacidosis is the combination of relative insulin deficiency and increased secretion of glucagon (as well as other counteregulatory hormones such as cortisol, catecholamines, and growth hormone) in response to stress from 1 ) overwhelming infection, 2 ) infarction of tissue, or 3 ) other severe illness. The elevated catecholamines further suppress insulin secretion to perpetuate a downward spiral. The increased glucagons-to-insulin ratio causes a mismatch that promotes unregulated lipolysis and proteolysis with subsequent uninterrupted formation of ketoacids.

To summarize, DKA is not a unique feature of type 1 diabetes. Though much more common in type 1 diabetes, it does occur in patients with type 2 diabetes, as illustrated by these case reports. However, it is rare for DKA to occur in type 2 diabetes in the absence of some precipitating event. When DKA occurs in an individual with type 2 diabetes, the clinician should “look under the sheets” and initiate an intensive search for the precipitating factor. Once identified, the trigger should be treated promptly and appropriately.

DKA does occur in type 2 diabetes.

DKA in type 2 diabetes rarely occurs without a trigger.

When it does, an intensive search for the precipitating factor should be undertaken.

Brian J. Welch, MD, and Ivana Zib, MD, are fellows in the Division of Endocrinology and Metabolism at the University of Texas Southwestern Medical Center in Dallas.

The authors thank Philip Raskin, MD, for his support and guidance.

Email alerts

• Online ISSN 1945-4953
• Print ISSN 0891-8929
• Diabetes Care
• Clinical Diabetes
• Diabetes Spectrum
• Standards of Medical Care in Diabetes
• Scientific Sessions Abstracts
• BMJ Open Diabetes Research & Care
• ShopDiabetes.org
• ADA Professional Books

Clinical Compendia

• Clinical Compendia Home
• Latest News
• DiabetesPro SmartBrief
• Special Collections
• DiabetesPro®
• Diabetes Food Hub™
• Insulin Affordability
• Know Diabetes By Heart™
• About the ADA
• Journal Policies
• For Reviewers
• Advertising in ADA Journals
• Reprints and Permission for Reuse
• Copyright Notice/Public Access Policy
• ADA Professional Membership
• ADA Member Directory
• Diabetes.org
• X (Twitter)
• Cookie Policy
• Accessibility
• Terms & Conditions
• Get Adobe Acrobat Reader
• © Copyright American Diabetes Association

This Feature Is Available To Subscribers Only

Sign In or Create an Account

Avail our cheap essay writer service in just 4 simple steps

To describe something in great detail to the readers, the writers will do my essay to appeal to the senses of the readers and try their best to give them a live experience of the given subject.

Customer Reviews

Customer Reviews

Finished Papers

2269 Chestnut Street, #477 San Francisco CA 94123

We are inclined to write as per the instructions given to you along with our understanding and background research related to the given topic. The topic is well-researched first and then the draft is being written.

Courtney Lees

Dr.Jeffrey (PhD)