A 25-year-old graduate student presented to the endocrine clinic with insidious onset of recurrent hypoglycemia. She was diagnosed with type 1 diabetes 7 months prior, following an episode of mild diabetic ketoacidosis (DKA) successfully treated in the emergency department (ED).
She initiated basal bolus insulin therapy with dramatic improvement in her HbA1c from 13.4% at diagnosis to 6.1% within a few months after starting insulin therapy. Her initial labs confirmed type 1a diabetes with a markedly elevated glutamic acid decarboxylase-65 antibody titer and a low, but not entirely undetectable, C-peptide level of 0.32 ng/mL. She is otherwise healthy without other medications or comorbidities, except for a daily oral contraceptive pill. Her BMI is 22 and her total daily insulin dose was 0.4 units/kg at the time of follow-up 3 months after her initial diagnosis.
Within a few months after diagnosis, a personal continuous glucose monitoring device (CGM) was prescribed, which measures glucose changes in the interstitial fluid in the subcutaneous tissue. CGM is often a useful adjunct for close glucose monitoring in an active young individual with type 1 diabetes.
The graphics below portray her CGM data over a period of 7 days, reporting each day’s glucose trend in increments of 5 minutes (Figures 1 and 2). The graphics are designed to highlight glycemic patterns that may suggest areas for improvement or targeting possible therapeutic changes with average, median and quartile data reported for the period. CGM data is particularly useful to supplement fingerstick glucose values, especially in the overnight and postprandial period. The green shaded box represents interstitial glucose values between 70 mg/dL and 180 mg/dL.
The most remarkable feature of the graphics below is the relative lack of hyperglycemic excursions, especially in the postprandial periods a few hours after breakfast and lunch. Overnight, there is a substantial downward trend in glucose levels from around midnight until 6 a.m. Taken as a collective, in addition to the clinical scenario, these CGM tracings are indicative of endogenous insulin reserve and residual beta cell function. In this specific patient, it heralded the onset of a “honeymoon” period.
Contrast these graphics with those below (Figures 3 and 4), which belong to a similar patient with type 1 diabetes of over 20 years duration and a similar HbA1c of 6.3%, using the same personal CGM system on an ongoing basis.
The major distinguishing feature to note here is the marked hyperglycemia and variability in glucose excursions after meals, which is typical of insulin-deficient patients with long standing type 1 diabetes. Post-breakfast hyperglycemia can be particularly problematic for many individuals with type 1 diabetes. This pattern is often associated with reduced insulin sensitivity in the early morning hours and the typical highly refined carbohydrate diets consumed in the United States at breakfast.
‘Honeymoon’ in Type 1 Diabetes
The so-called “honeymoon” period in type 1 diabetes is characterized by reduced exogenous insulin requirements while glycemic control is well maintained (i.e., partial remission.) It may develop relatively soon after the diagnosis of autoimmune diabetes and is regarded as a transient phase of remission occurring due to the development of adaptive immune tolerance and possibly related to improvement in beta cell function after resolution of acute glucose toxicity. It is associated with significant residual endogenous insulin production mirrored by a decreased need for exogenous insulin.
This process has been clinically defined in various ways. A practical clinical approach may be to consider this diagnosis when the total daily insulin dose is less than 0.5 units/kg body weight per day while still resulting in an HbA1c of less than 7%.1 Alternatively, a daily insulin dose of less than 0.3 units/kg body weight per day resulting in an HbA1c of less than 6% may be considered a more stringent definition.2
The honeymoon phase can occur in up to 80% of newly diagnosed individuals with autoimmune diabetes. However, the degree and durability of endogenous insulin reserve is highly variable. Young children, those with longer duration of symptoms prior to diabetes diagnosis and those presenting with more severe disease at onset are less likely to enter remission. Male sex, older age at onset of disease and absence of frank ketoacidosis are factors predictive of remission. There are individuals who are able to discontinue all exogenous insulin entirely for a period of months.2
This report serves to highlight the relatively novel value of CGM technology in helping to recognize the onset of partial remission of diabetes. The relative lack of glycemic variability and postprandial hyperglycemic excursions in addition to low total daily insulin dose, in comparison to a similarly well controlled patient many years after diagnosis, highlights the distinction and the onset of honeymoon in type 1 diabetes.
- Lombardo F, Valenzise M, Wasniewska M, Messina MF, Ruggeri C, Arrigo T et al. Two-year prospective evaluation of the factors affecting honeymoon frequency and duration in children with insulin dependent diabetes mellitus: The key-role of age at diagnosis. Diabetes Nutr Metab. 2002;15(4):246–251
- Bonfanti R, Bazzigaluppi E, Calori G, Riva MC, Viscardi M, Bognetti E et al. Parameters associated with residual insulin secretion during the first year of disease in children and adolescents with Type 1 diabetes mellitus. Diabet Med. 1998;15:844–50.