Glucoregulation in Normoglycemic Subjects with or without Parental Diabetes: Data from Euglycemic Clamp Studies

Presentation Number: MON 577
Date of Presentation: April 3rd, 2017

Ebenezer A Nyenwe*1, Jim Wan2 and Samuel Dagogo-Jack3
1Division of Endocrinology, Diabetes & Metabolism, Memphis, TN, 2The University of Tennessee Health Science Center, Memphis, TN, 3University of Tennessee, Memphis, TN

Abstract

Type 2 diabetes (T2DM) is preceded by prediabetes, a reversible metabolic state associated with increased cardiovascular risk. The mechanisms for progression from prediabetes to diabetes has been studied, but the factors which trigger the escape from normoglycemia to prediabetes remain unclear. Offspring of diabetic parents and ethnic minority groups have a higher predilection to T2DM but the progression from prediabetes to diabetes showed no ethnic disparity. We hypothesized that genetic predisposition would allow detection of early glucoregulatory impairments in normoglycemic offspring of diabetic parents. To investigate the influence of parental diabetes on glucoregulation in euglycemic subjects, we studied 50 offspring of diabetic parents who were matched for age, sex, ethnicity and BMI with 50 subjects without parental diabetes. Subjects underwent 75 g OGTT, with blood sampling at 0, 30 and 120 minutes after ingestion of glucose. We estimated acute insulin secretion by IVGTT using 25 g glucose and we measured whole body insulin sensitivity (ISI) by euglycemic clamp. Hepatic insulin resistance was assessed by HOMA-IR while basal Insulin secretion was estimated by HOMA-B. β-cell function was evaluated by disposition index. Data were analyzed using Students’ t-test.

Offspring of diabetic parents had higher insulin resistance: HOMA-IR (1.85 ± 1.72 vs 0.99 ± 0.86, P<0.001); ISI (0.132 ± 0.068 vs 0.162 ± 0.081, P<0.05) and increased basal insulin secretion: fasting insulin (8.12 ± 7.34 vs 4.39 ± 3.65, P<0.01); HOMA-B (103.8 ± 83.7 vs 59.9 ±45.2, P<0.001); but acute insulin response was comparable in both groups (79.96 ± 62.77 vs 88.18 ± 70.94, P>0.5). β-cell function (disposition index) was higher in subjects without parental diabetes (11.83 ± 7.48 vs 8.74 ± 5.72 P<0.05). Glucose tolerance was discordant between the two groups with higher glycemic excursion during OGTT occurring in offspring of diabetic parents: 2-hours post glucose load (126.8 ± 31.7 vs 113.1 ± 19.2 P<0.01); area under the curve for glucose (14,973.81 ± 1,819.94 vs 16,005.57 ± 2,324.68 P<0.01), HbA1c (5.61 ± 0.47 vs 5.36 ± 0.40 P<0.01). Subjects with parental diabetes also showed a tendency towards a higher respiratory quotient (1.07 ± 0.30 vs 0.98 ± 0.10 P=0.07). We have demonstrated that defects in insulin action and secretion are evident in the normoglycemic phase in subjects with parental diabetes. These defects may represent the earliest impairment in the evolution of dysglycemia and could offer opportunity for prevention of prediabtes.

 

Nothing to Disclose: EAN, JW, SD