What does persistent ketonuria in a pregnant diabetic patient with well-controlled blood glucose levels indicate?

From the Guidelines

Persistent ketones in the urine of a pregnant diabetic woman despite normal blood sugar levels may indicate starvation ketosis rather than diabetic ketoacidosis, and to address this, pregnant diabetic women should eat small, frequent meals throughout the day, including a bedtime snack containing both protein and complex carbohydrates, as recommended by the most recent guidelines 1. This phenomenon is more pronounced in diabetic pregnancies due to the body's natural state of accelerated starvation between meals, leading to faster depletion of glycogen stores and earlier transition to fat metabolism, producing ketones. Some key points to consider include:

• Pregnancy is a ketogenic state, and people with type 1 diabetes, and to a lesser extent those with type 2 diabetes, are at risk for diabetic ketoacidosis (DKA) at lower blood glucose levels than in the nonpregnant state 1.
• Education for people with diabetes and family members about the prevention, recognition, and treatment of hypoglycemia is important before, during, and after pregnancy to help prevent and manage hypoglycemia risk 1.
• While some level of ketones may be normal during pregnancy, persistent high levels should be reported to healthcare providers as they could potentially affect fetal development.
• Blood ketone monitoring might be recommended in addition to urine testing for more accurate assessment, and if ketones persist despite dietary changes, the healthcare provider might need to adjust insulin regimens or evaluate for other underlying issues. Adequate hydration is also important, and pregnant diabetic women should be advised to obtain ketone test strips and receive education on DKA prevention and detection 1. The current recommended amount of carbohydrate is 175 g, or 35% of a 2,000-calorie diet, and liberalizing higher quality, nutrient-dense carbohydrates results in controlled fasting/postprandial glucose, lower free fatty acids, improved insulin action, and vascular benefits and may reduce excess infant adiposity 1. Fasting urine ketone testing may be useful to identify women who are severely restricting carbohydrates to control blood glucose, and simple carbohydrates will result in higher post-meal excursions 1. Reflecting the physiology of pregnancy, fasting and postprandial blood glucose monitoring is recommended to achieve metabolic control in pregnant people with diabetes, and preprandial testing is also recommended when using insulin pumps or basal-bolus therapy so that premeal rapid-acting insulin dosage can be adjusted 1. An expert panel on nutrition in pregnancy recommends a balance of macronutrients, and a diet that severely restricts any macronutrient class should be avoided, specifically the ketogenic diet that lacks carbohydrates, the Paleo diet because of dairy restriction, and any diet characterized by excess saturated fats 1. Nutrient-dense, whole foods are recommended, including fruits, vegetables, legumes, whole grains, and healthy fats with n-3 fatty acids that include nuts and seeds and fish, which are less likely to promote excessive weight gain, and processed foods, fatty red meat, and sweetened foods and beverages should be limited 1.

From the Research

Ketones in Pregnant Diabetic Urine

• The presence of ketones in the urine of a pregnant diabetic woman, despite good blood sugar control, can be an indication of several factors, including insulin resistance, accelerated starvation, and respiratory alkalosis, which can create a ketosis-prone state 2.
• Euglycemic diabetic ketoacidosis (DKA) is a condition where ketones are present in the urine, even when blood glucose levels are normal, and can occur in pregnant women with diabetes 3, 4.
• The presence of ketonuria (ketones in the urine) is more common than ketonemia (ketones in the blood) in women with gestational diabetes mellitus (GDM) who are on a diet 5.
• Ketone bodies are an energy substrate produced by the liver and used during states of low carbohydrate availability, and high ketone concentrations can be present with insulin insufficiency and are a key finding in DKA 6.

Possible Causes and Triggers

• Insulin resistance and accelerated starvation can contribute to the development of ketosis in pregnant women with diabetes 2.
• Infections, poor adherence to treatment, and other factors can trigger DKA in pregnant women with diabetes 4.
• Weight loss per week was found to be an independent predictor of increased 3-hydroxybutyrate (3HB) levels in women with GDM 5.

Measurement and Diagnosis

• The use of capillary blood 3-β-hydroxybutyrate (3HB) is a more precise method than urine ketones measurement for the diagnosis of DKA 5.
• Point-of-care tests are available for self-testing of blood ketones and urine ketones, and can be helpful in assessing compliance with low carbohydrate diets and identifying DKA due to insulin deficiency 6.