An evaluation of early cardiometabolic risk factors in children and adolescents with Turner syndrome

O’Gorman, Clodagh S.; Syme, Catriona; Lang, Jun; Bradley, Timothy J.; Wells, Greg D.; Hamilton, Jill

doi:10.1111/cen.12079

Cited by 63 publications

(86 citation statements)

References 31 publications

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“…The serial assessments of the current protocol were essential for elucidating the patterns of change over time described in this report. Moreover, the ISSI-2 and Matsuda index are validated measures that have been widely used in previous studies (17,(23)(24)(25)(26)(27)(28)(29)(30), and the serial OGTTs on which they were determined made it possible to also assess glucose tolerance status.…”

Section: Discussionmentioning

confidence: 99%

“…b-Cell function was assessed on each OGTT with the Insulin SecretionSensitivity Index-2 (ISSI-2), a validated measure of b-cell function that is analogous to the disposition index obtained from the intravenous GTT (IVGTT) (24,25). The ISSI-2 has been directly validated against the disposition index from the IVGTT, with which it exhibits stronger correlation than do other OGTTderived measures of b-cell function, including the insulinogenic index-based measures and HOMA b-cell (HOMA-B) function, (25) and has been used in clinical trials and observational studies in patients with and without diabetes (17,(26)(27)(28)(29)(30). ISSI-2 is defined as the product of 1) insulin secretion measured by the ratio of the area-under-the-insulin curve to the area-under-the-glucose curve and 2) insulin sensitivity measured by Matsuda index (24,25).…”

Section: Laboratory Measurements and Physiologic Indicesmentioning

confidence: 99%

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Each Degree of Glucose Intolerance in Pregnancy Predicts Distinct Trajectories of β-Cell Function, Insulin Sensitivity, and Glycemia in the First 3 Years Postpartum

et al. 2014

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OBJECTIVEGlucose intolerance in pregnancy predicts an increased risk of future type 2 diabetes mellitus (T2DM) that is proportional to the severity of antepartum dysglycemia (i.e., highest in women with gestational diabetes mellitus [GDM], followed by those with milder dysglycemia). However, the pathophysiologic changes driving this risk are not known. Thus, we evaluated the longitudinal changes in b-cell function, insulin sensitivity, and glycemia in the first 3 years postpartum after gestational dysglycemia. RESEARCH DESIGN AND METHODSA total of 337 women underwent glucose challenge test (GCT) and oral glucose tolerance test (OGTT) in pregnancy, followed by repeat OGTT at 3 months, 1 year, and 3 years postpartum. The antepartum GCT/OGTT identified four gestational glucose tolerance groups: GDM (n = 105); gestational impaired glucose tolerance (GIGT; n = 60); abnormal GCT, followed by normal glucose tolerance (NGT) on the OGTT (abnormal GCT NGT; n = 96); and normal GCT with NGT (n = 76). RESULTSAt each of 3 months, 1 year, and 3 years postpartum, the prevalence of glucose intolerance increased from normal GCT NGT to abnormal GCT NGT to GIGT to GDM (all P < 0.001), whereas b-cell function, assessed by the Insulin SecretionSensitivity Index-2 (ISSI-2), and insulin sensitivity (Matsuda index), progressively decreased across the groups (all P < 0.002). Each group predicted distinct trajectories of ISSI-2, Matsuda index, and fasting and 2-h glucose (all P < 0.001). Notably, GDM, GIGT, and abnormal GCT NGT predicted varying rates of declining b-cell function and insulin sensitivity, as well as rising glycemia, compared with normal GCT NGT. CONCLUSIONSEach degree of gestational glucose intolerance predicts distinct trajectories of b-cell function, insulin sensitivity, and glycemia in the first 3 years postpartum that drive their differential risk of future T2DM.

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Section: Discussionmentioning

confidence: 99%

Section: Laboratory Measurements and Physiologic Indicesmentioning

confidence: 99%

Each Degree of Glucose Intolerance in Pregnancy Predicts Distinct Trajectories of β-Cell Function, Insulin Sensitivity, and Glycemia in the First 3 Years Postpartum

et al. 2014

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“…Lastly, b-cell function and insulin sensitivity were assessed with surrogate indices, rather than more time-consuming and cumbersome clamp studies, which would have been difficult to implement in 494 new mothers on two occasions in the first year after delivery. Moreover, ISSI-2 and Matsuda index are validated measures that have been widely used in previous studies (10,11,23,(32)(33)(34)(35).…”

Section: Discussionmentioning

confidence: 99%

“…ISSI-2 is a validated measure of b-cell function that is analogous to the disposition index obtained from the intravenous glucose tolerance test (30,31). ISSI-2 has been directly validated against the disposition index from the intravenous glucose tolerance test, with which it exhibits stronger correlation than do other OGTT-derived measures of b-cell function (31), and has been used to measure b-cell function in several previous studies, including both clinical trials and observational studies (10,23,(32)(33)(34)(35). ISSI-2 is defined as the product of 1) insulin secretion measured by the ratio of AUC ins to AUC gluc and 2) insulin sensitivity measured by Matsuda index (30,31).…”

Section: Laboratory Measurements and Physiologic Indicesmentioning

confidence: 99%

Prospective Associations of Vitamin D Status With β-Cell Function, Insulin Sensitivity, and Glycemia: The Impact of Parathyroid Hormone Status

et al. 2014

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Previous studies have yielded conflicting findings on the relationship between low vitamin D (25-OH-D) and impaired glucose homeostasis. In this context, we hypothesized that combined assessment of 25-OH-D with its regulator parathyroid hormone (PTH) may be required for optimal evaluation of the impact of vitamin D status on glucose metabolism. Thus, we evaluated the prospective associations of 25-OH-D and PTH at 3 months postpartum with b-cell function (Insulin SecretionSensitivity Index-2 [ISSI-2]), insulin sensitivity (Matsuda index), and glycemia at 12 months postpartum in 494 women undergoing serial metabolic characterization. Notably, 32% of those with prediabetes/diabetes mellitus at 12 months postpartum had both vitamin D deficiency and PTH in the highest tertile at 3 months postpartum. On multiple-adjusted linear regression analyses, vitamin D deficiency/insufficiency with PTH in the highest tertile at 3 months independently predicted poorer b-cell function (P = 0.03) and insulin sensitivity (P = 0.01) and increased fasting (P = 0.03) and 2-h glucose (P = 0.002) at 12 months postpartum. In contrast, vitamin D deficiency/insufficiency with lower PTH did not predict these outcomes. In conclusion, only vitamin D deficiency/insufficiency with increased PTH is an independent predictor of b-cell dysfunction, insulin resistance, and glycemia, highlighting the need for consideration of the PTH/25-OH-D axis when studying the impact of vitamin D status on glucose homeostasis.

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“…As previously described (22), b-cell function was assessed on each OGTT with the Insulin Secretion-Sensitivity Index-2 (ISSI-2), a validated OGTTderived measure of b-cell function that is analogous to the disposition index obtained from the intravenous glucose tolerance test (25,26). ISSI-2 has been directly validated against the disposition index from the intravenous glucose tolerance test, with which it exhibits a stronger correlation than other OGTTderived measures of b-cell function (including insulinogenic index-based measures and the homeostasis model assessment [HOMA] of b-cell function ) (26), and has been used to measure b-cell function in several previous studies, including both clinical trials and observational studies in patients with and without diabetes (22,(26)(27)(28)(29)(30)(31). ISSI-2 is defined as the product of 1) insulin secretion measured by the ratio of AUC ins to AUC gluc and 2) insulin sensitivity measured by the Matsuda index (25,26), such that ISSI-2 = (AUC ins / AUC gluc ) 3 Matsuda index.…”

Section: Assessment Of Glucose Variabilitymentioning

confidence: 99%

Glycemic Variability in Patients With Early Type 2 Diabetes: The Impact of Improvement in β-Cell Function

et al. 2014

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OBJECTIVEIncreased glycemic variability has been reported to be associated with the risk of hypoglycemia and possibly diabetes complications and is believed to be due to b-cell dysfunction. However, it is not known whether improvement in b-cell function can reduce glycemic variability. Because short-term intensive insulin therapy (IIT) can improve b-cell function in early type 2 diabetes (T2DM), our objective was to determine whether the b-cell functional recovery induced by this therapy is associated with decreased glycemic variability. RESEARCH DESIGN AND METHODSSixty-one patients with T2DM of 3.0 years mean duration underwent 4 weeks of IIT, which consisted of basal insulin detemir and premeal insulin aspart. Glucose variability was assessed in both the first and the last week by the coefficient of variation of capillary glucose on daily 6-point self-monitoring profiles. b-Cell function before and after IIT was assessed with the Insulin Secretion-Sensitivity Index-2 (ISSI-2). RESULTSBetween the first and the last week on IIT, 55.7% of patients had a reduction in glucose variability. Change in glucose variability was negatively correlated with the change in b-cell function (ISSI-2) (r = 20.34, P = 0.008). On multiple linear regression analyses, percentage change in ISSI-2 emerged as the only factor independently associated with the change in glucose variability (standardized b = 20.42, P = 0.03). Moreover, patients with an increase in ISSI-2 ‡25% experienced a reduction in glucose variability compared with their peers who had almost no change (20.041 6 0.06 vs. 20.0002 6 0.04, respectively; P = 0.006). CONCLUSIONSIn early T2DM, glycemic variability is a modifiable parameter that can be reduced by improving b-cell function with short-term IIT.

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An evaluation of early cardiometabolic risk factors in children and adolescents with Turner syndrome

Abstract: TS girls exhibit more cardiometabolic risk factors and reduced beta cell function compared with age- and BMI-SDS-matched girls. Increased awareness of early risk of type 2 diabetes mellitus and hypertension in TS girls is needed.

Cited by 63 publications

References 31 publications

Each Degree of Glucose Intolerance in Pregnancy Predicts Distinct Trajectories of β-Cell Function, Insulin Sensitivity, and Glycemia in the First 3 Years Postpartum

Each Degree of Glucose Intolerance in Pregnancy Predicts Distinct Trajectories of β-Cell Function, Insulin Sensitivity, and Glycemia in the First 3 Years Postpartum

Prospective Associations of Vitamin D Status With β-Cell Function, Insulin Sensitivity, and Glycemia: The Impact of Parathyroid Hormone Status

Glycemic Variability in Patients With Early Type 2 Diabetes: The Impact of Improvement in β-Cell Function

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