Fetal exposure to maternal type 1 diabetes is associated with renal dysfunction at adult age

Abstract

Objective: In animal studies, hyperglycemia during fetal development reduces nephron numbers. We tested whether this observation translates into renal dysfunction in humans by studying renal functional reserve in adult offspring exposed in utero to maternal type 1 diabetes.

Research design and methods: We compared 19 nondiabetic offspring of type 1 diabetic mothers with 18 offspring of type 1 diabetic fathers (control subjects). Glomerular filtration rate ((51)Cr-EDTA clearance), effective renal plasma flow ((123)I-hippurate clearance), mean arterial pressure, and renal vascular resistances were measured at baseline and during amino acid infusion, which mobilizes renal functional reserve.

Results: Offspring of type 1 diabetic mothers were similar to control subjects for age (median 27, range 18-41, years), sex, BMI (23.1 ± 3.7 kg/m(2)), and birth weight (3,288 ± 550 vs. 3,440 ± 489 g). During amino acid infusion, glomerular filtration rate and effective renal plasma flow increased less in offspring of type 1 diabetic mothers than in control subjects: from 103 ± 14 to 111 ± 17 ml/min (8 ± 13%) vs. from 108 ± 17 to 128 ± 23 ml/min (19 ± 7%, P = 0.009) and from 509 ± 58 to 536 ± 80 ml/min (5 ± 9%) vs. from 536 ± 114 to 620 ± 140 ml/min (16 ± 11%, P = 0.0035). Mean arterial pressure and renal vascular resistances declined less than in control subjects: 2 ± 5 vs. -2 ± 3% (P = 0.019) and 3 ± 9 vs. -14 ± 8% (P = 0.001).

Conclusions: Reduced functional reserve may reflect a reduced number of nephrons undergoing individual hyperfiltration. If so, offspring of type 1 diabetic mothers may be predisposed to glomerular and vascular diseases.

FIG. 1.

Kidney function of offspring of type 1 diabetic mothers (case subjects, left) and of offspring of type 1 diabetic fathers (control subjects, right) in basal conditions and during infusion of amino acids (stimulated). Data are given as median values with box plots and individual values. A: Changes in glomerular filtration rate (GFR), intragroup changes in case subjects: 8 ± 13%, P = 0.019, and in control subjects: 19 ± 17%, P = 0.002, intergroup comparison: P = 0.009. B: Changes in effective renal plasma flow (ERPF), intragroup changes in case subjects: 5 ± 9%, P = 0.016, and in control subjects: 16 ± 11%, P = 0.002, intergroup comparison: P = 0.0035. C: Changes in FF, intragroup changes in case subjects: 3 ± 8%, P = 0.14, and in control subjects: 3 ± 8%, P = 0.26, intergroup comparisons: P = 0.92. D: Changes in mean arterial pressure (MAP), intragroup changes in case subjects: 2 ± 5%, P = 0.061, and in control subjects: −2 ± 3%, P = 0.029, intergroup comparison: P = 0.019. E: Changes in renal vascular resistances (RVR), intragroup changes in case subjects: −3 ± 9%, P = 0.1, and in control subjects: −14 ± 8%, P = 0.002, intergroup comparison: P = 0.001.

FIG. 2.

Relationship between birth weight and GFR relative changes during tests in the offspring of type 1 diabetic mothers (left panel) and of type 1 diabetic fathers (right panel). Solid lines represent the regression lines, and dashed lines represent the 95% prediction intervals. Pearson correlation coefficient in offspring of type 1 diabetic mothers: r = 0.61 (P = 0.006); in offspring of type 1 diabetic fathers: r = −0.08 (P = 0.76).