Longitudinal MRI Shows Progressive Decline in Pancreas Size and Altered Pancreas Shape in Type 1 Diabetes

Abstract

Context: Individuals with type 1 diabetes (T1D) have a smaller pancreas, but longitudinal changes in pancreas size and shape are unclear.

Objective: We monitored changes in pancreas size and shape after diagnosis with T1D.

Design: We conducted a prospective cohort study at an academic medical center between 2014 and 2022.

Patients and healthy controls: Individuals with T1D (n = 91) or controls (n = 90) underwent magnetic resonance imaging (MRI) of the pancreas, including longitudinal MRI in 53 individuals with new-onset T1D.

Intervention: Interventions included MRI and continuous glucose monitoring (CGM).

Main outcome measures: Pancreas size and shape were measured from MRI. For participants who used CGM, measures of glycemic variability were calculated.

Results: On longitudinal imaging, pancreas volume and pancreas volume index normalized for body weight declined during the first year after diagnosis. Pancreas volume index continued to decline through the fifth year after diagnosis. A cross-sectional study of individuals with diabetes duration up to 60 years demonstrated that pancreas size in adults negatively correlated with age and disease duration, whereas pancreas volume and pancreas volume index remained stable in controls. Pancreas volume index correlated inversely with low blood glucose index, a measure of risk for hypoglycemia. Pancreas shape was altered in individuals with T1D and further diverged from controls over the first 5 years after diagnosis. Pancreas size and shape are altered in nondiabetic individuals at genetic risk for T1D. Combined pancreas size and shape analysis better distinguished the pancreas of individuals with T1D from controls than size alone.

Conclusions: Pancreas size declines most rapidly near the clinical diagnosis of T1D and continues to decline throughout adulthood. Declines in pancreas size are accompanied by changes in pancreas shape.

Trial registration: ClinicalTrials.gov NCT03585153.

Keywords: MRI; morphology; morphometry; pancreas volume; surface area; type 1 diabetes.

Figure 1.

Longitudinal measurement of pancreas volume in recently diagnosed type 1 diabetes. (A) Pancreas volume declines most rapidly during the first year after diagnosis and levels off in the following years. (B) Proximal pancreas volume declines during the first year after diagnosis and stabilizes thereafter. (C) Distal pancreas volume declines during the first year after diagnosis and levels off in the following years. (D) Pancreas volume index, which is normalized for body weight, declines most rapidly in the first year after diagnosis with continued decline in the following years. (E) The rate of decline in pancreas volume index in the year after diagnosis is most rapid in individuals who had a large pancreas volume index at diagnosis. (F) Small pancreas volume index correlated with greater risk for hypoglycemia, as assessed by Low Blood Glucose Index.

Figure 2.

Assessment of pancreas volume in short- and long-standing T1D. (A) Pancreas volume correlates with age through the first 20 years of life in individuals with T1D and controls, followed by a plateau in adult controls and inverse correlation with age in adults with T1D. (B) Pancreas volume index, which accounts for adolescent weight gain, is inversely correlated with age in individuals with T1D but is stable in control individuals. Pancreas volume (C) and pancreas volume index (D) are inversely correlated with duration of T1D in adult study participants. Abbreviations: T1D, type 1 diabetes.

Figure 3.

(A) There is no difference in the ratio of the distal to proximal pancreas volume between individuals with and without T1D. (B) Individuals with T1D have a larger pancreas surface area to volume ratio than controls without diabetes. (C) The volume of a bounding box, (D) fraction of bounding box filled with pancreas, and (E) fraction of bounding box filled with pancreas are all smaller in individuals with T1D. The (F) longest, (G) second longest, and (H) shortest principal axes of an ellipsoid aligned with the pancreas are shorter in individuals with T1D. (I) The ratio of the longest to shortest principal axis is greater in individuals with T1D, suggesting a greater decline in pancreas circumference than the long axis spanning the pancreas head to tail. Abbreviations: T1D, type 1 diabetes.

Figure 4.

Individuals with type 1 diabetes (top row) have a thinner pancreas than individuals without diabetes (bottom row). The three-dimensional shape of the pancreas can be quantified using a bounding box (left column), bounding convex hull (middle column), or the principal axes of an ellipsoid aligned with the pancreas (right column).

Figure 5.

(A) Relative pancreas surface area to volume ratio tends to increase during the first 5 years after diagnosis with T1D. The relative fraction of a (B) bounding box and (C) bounding convex hull filled with pancreas declines with increasing duration of T1D. (D) The relative ratio of the longest to shortest principal axis increases with disease duration. Abbreviations: T1D, type 1 diabetes.

Figure 6.

(A) A correlation plot of pancreas volume index and the 11 shape variables employed in this study shows correlations between size and shape variables. Significant correlations are noted with asterisks: ***, P < .001; **, P < .01; *, P < .05. (B) Receiver operating characteristic curves for classifying individuals with T1D vs controls demonstrate a higher AUC for pancreas shape and pancreas volume index (AUC = 0.92) than pancreas volume index alone (AUC = 0.88, P < .01). The pancreas shape and volume index model includes pancreas volume index, pancreas surface area to volume ratio, the fraction of bounding convex hull filled, longest to shortest principal axis ratio, longest to second longest principal axis ratio, and the interaction between pancreas volume index and fraction of bounding hull filled. Abbreviations: AUC, area under the curve; T1D, type 1 diabetes.