A 24-year-old postpartum woman comes to the office for follow-up of gestational diabetes. The patient was diagnosed with gestational diabetes mellitus during routine screening at 28 weeks gestation; she was treated with dietary modification and exercise and required insulin briefly. Since delivery 12 weeks ago, she has continued to follow dietary recommendations, and her blood glucose has been fairly well controlled without insulin. The patient has fasting blood glucose levels of 100-120 mg/dL. Medical history is otherwise unremarkable. Family history is significant for diabetes mellitus in her mother and gestational diabetes in her sister. Vital signs are within normal limits. BMI is 22 kg/m². Physical examination shows no abnormalities. Her gestational diabetes and fasting hyperglycemia are suspected to be genetically predisposed. This patient's condition is most likely caused by reduced activity of which of the following enzymes?

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11ec160b_36c7_af00_9249_1dd22c191fdc_MD0001_00 Glucose-induced insulin release from pancreatic beta cells requires the following steps: Glucokinase has a lower glucose affinity than other hexokinases, which allows it to limit the rate of glucose entry into the glycolytic pathway based on blood glucose levels. It therefore functions as a glucose sensor for beta cells in controlling insulin release. Heterozygous mutations of the glucokinase gene that decrease the activity or affinity of the enzyme cause a decrease in beta cell glucose metabolism, leading to reduced ATP formation and insulin secretion at any given glucose level. Glucokinase mutations are one cause of maturity-onset diabetes of the young (MODY), an autosomal dominant disorder characterized by mild hyperglycemia that often worsens with pregnancy-induced insulin resistance. In contrast to those with more common type 2 diabetes mellitus, patients with MODY are typically younger and nonobese, and the condition is nonprogressive, even without treatment. (Choices A, B, E, and G) Glycolytic enzyme deficiencies (eg, aldolase A, enolase, phosphofructokinase, pyruvate kinase) generally present with hemolytic anemia because red blood cells rely completely on anaerobic glycolysis for energy production. (Choice D) Lactate dehydrogenase is present in most cells and catalyzes the conversion of pyruvate to lactate during anaerobic glycolysis. Deficiency can cause decreased exercise tolerance and muscle stiffness. (Choice F) Pyruvate carboxylase, one of the gluconeogenesis pathway enzymes in the mitochondria, catalyzes the conversion of pyruvate to oxaloacetate. Deficiency of pyruvate carboxylase causes lactic acidosis and fasting hypoglycemia. Educational objective: Insulin release by pancreatic beta cells is stimulated by increased glucose metabolism and ATP production. Glucokinase functions as a glucose sensor in pancreatic beta cells by controlling the rate of glucose entry into the glycolytic pathway. Mutations in the glucokinase gene lead to a state in which higher glucose levels are required to stimulate insulin secretion and are a cause of maturity-onset diabetes of the young. __________ References: Glucokinase MODY and implications for treatment goals of common forms of diabetes. (http://www.ncbi.nlm.nih.gov/pubmed/25344793)

A 24-Year-Old Postpartum Woman Comes to the Office for Follow-Up