Impaired Insulin Secretion in the Turner Metabolic Syndrome

Abstract

An increased prevalence of impaired glucose homeostasis (IGH) and diabetes mellitus is reported in monosomy X, or Turner syndrome (TS). To determine whether IGH is an intrinsic feature of this syndrome, independent of obesity or hypogonadism, we compared results of a standard oral glucose challenge in age- and body mass index-matched women with TS and with karyotypically normal premature ovarian failure (POF). Fasting glucose levels were normal in both groups, but glucose values after oral glucose challenge were higher in TS [2-h glucose, 135 +/- 36 mg/dl (7.5 +/- 2.0 mmol/liter) in TS and 97 +/- 18 mg/dl (5.4 +/- 1.0 mmol/liter) in POF; P < 0.0001]. Glucose-stimulated insulin secretion was lower in TS; e.g. the initial insulin response (DeltaI/DeltaG(30)) was decreased by 60% compared with POF (P < 0.0001). We also compared responses to a standard iv glucose tolerance test in women with TS and in age- and body mass index-matched normal women and found that the insulin area under the curve was 50% lower in women with TS (P = 0.003). Insulin sensitivity measured by the quantitative insulin sensitivity check index was higher in women with TS compared with both control groups. Thus, IGH is not secondary to obesity or hypogonadism in TS, but it is a distinct entity characterized by decreased insulin secretion, suggesting that haploinsufficiency for X-chromosome gene(s) impairs beta-cell function and predisposes to diabetes mellitus in TS.

Metabolic aspects of pig-to-monkey (Macaca fascicularis) islet transplantation: implications for translation into clinical practice

“…injection of glucose at 0.3 or 0.5 g/kg showed C-peptide and insulin levels intermediate between those of pigs and monkeys. The fold increases between time 0 and 5 min and between time 0 and 15 min were (range) 2.5-3.5 and 2.1-3.0 respectively for C-peptide and 6.3-11.4 and 4.0-5.0 for insulin [24][25][26][27][28][29][30].…”

45,X/46,XX mosaicism below 30% of aneuploidy: clinical implications in adult women from a reproductive medicine unit

“…However, the hypothesis of gene haploinsufficiency for overweight was not upheld by Ohman et al because of a candidate locus for obesity located on X short arm Xp24 (21). Nevertheless, Bakalov et al demonstrated an insulin secretion defect in TS patients compared with both 46,XX patients with diminished ovarian reserve and controls matched according to age (22); they illustrated that haploinsufficiency of genes located on X chromosome accounted for pancreatic b-cell impairment. This finding could partly explain the positive correlation demonstrated in our study, with proportional pancreatic cell impairment depending on the percentage of aneuploidy.…”

Body composition is distinctly altered in Turner syndrome: relations to glucose metabolism, circulating adipokines, and endothelial adhesion molecules

“…Glucose metabolism is altered in TS and type 2 diabetes is seen frequently (9); insulin resistance has been reported in some studies on children (10,11), while studies on adults have pointed towards b-cell failure rather than insulin resistance as the primary defect in glucose homeostasis (5,12,13). The pathogenesis behind progressive b-cell failure is not clear, and further characterization is necessary.…”