Diabetes Mellitus

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Debate exists regarding the heights of children and adolescents with newly diagnosed Type 1 diabetes mellitus (IDDM) (32-34), however, it appears that growth deceleration may be seen prior to islet cell failure and overt symptoms of diabetes (35). Further, poor metabolic control of IDDM is associated with chronic elevation of serum GH concentration, growth retardation, and delayed sexual development (36,37). The metabolic effects of the elevated GH concentrations have been implicated as a causative factor in the development of diabetic retinopathy and other microvascular complications (38).

In 52 adolescents with IDDM, GH secretory dynamics and IGF binding proteins (IGFBPs) were assessed during puberty (39). Subjects were divided into two separate groups based on glycemic control. Using overnight GH sampling studies, no significant differences were found in the two groups with respect to total GH secretion, number of GH pulses, or GH peak amplitude. The data were similar to that seen in non-IDDM adolescents (39). Other investigators report diminished 125I-GH binding to the high-affinity GH binding protein (HA-GHBP), associated with higher random, unstimulated serum GH levels. The authors propose the existence of a serum GH inhibitor, which may reduce in vivo and in vitro binding of GH to its binding protein and thus impair its bioactivity (40). IGFBP3, the binding protein most closely correlated with GH secretion, was reduced in IDDM subjects during pubertal stages 3 and 5; no increase in IGFBP3 occurred with advancing age in contrast to controls. IGFBP1, a GH-independent binding protein, is inversely related to insulin concentration. IGFBP1 levels were elevated throughout puberty in diabetic subjects when compared with controls; IGFBP1 was positively correlated with hemoglobin A1C concentration in a subgroup of poorly controlled diabetics (hemoglobin A1C >8.5%), suggesting lower insulin levels. IGFBP1 has been demonstrated to inhibit growth of chicken embryo cartilage (39) and suppress IGF-1 bioactivity (41). Elevation of IGFBP1 and depression of IGFBP3 and IGF-1 in IDDM subjects with poor metabolic control may provide one explanation for poor linear growth.

Following a 4-wk period of intensive insulin and dietary intervention to improve glycemic control in six adolescents with poorly controlled IDDM, there was no change in the mean 24-h GH concentration, pulse frequency or amplitude. Serum IGF-I concentrations improved significantly, reflecting improved GH sensitivity and partial correction of a GH resistance-like state (37). Enhanced GH secretion in the face of chronic hyperglycemia and following GHRH administration appears consistent with a state of diminished somatostatin tone in subjects with diabetes (37).

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