Disposition index identifies defective beta-cell function in cystic fibrosis subjects with normal glucose tolerance

IntroductionRisk of insulin resistance, dyslipidemia, diabetes and cardiac death is increased in Asians and Europeans with normal glucose tolerance (NGT) and 1-hour glucose ≥8.6 mmol/L. As African descent populations often have insulin resistance but a normal lipid profile, the implications for Africans with NGT and glucose ≥8.6 mmol/L (NGT-1-hour-high) are unknown.ObjectiveWe performed oral glucose tolerance tests (OGTTs) in 434 African born-blacks living in Washington, DC (male: 66%, age 38±10 years (mean±SD)) and determined in the NGT group if either glucometabolic or lipid profiles varied according to a 1-hour-glucose threshold of 8.6 mmol/L.MethodsGlucose tolerance category was defined by OGTT criteria. NGT was subdivided into NGT-1-hour-high (glucose ≥8.6 mmol/L) and NGT-1-hour-normal (glucose <8.6 mmol/L). Second OGTT were performed in 27% (119/434) of participants 10±7 days after the first. Matsuda Index and Oral Disposition Index measured insulin resistance and beta-cell function, respectively. Lipid profiles were obtained. Comparisons were by one-way analysis of variance with Bonferonni corrections for multiple comparisons. Duplicate tests were assessed by к-statistic.ResultsOne-hour-glucose ≥8.6 mmol/L occurred in 17% (47/272) with NGT, 72% (97/134) with pre-diabetes and in 96% (27/28) with diabetes. Both insulin resistance and beta-cell function were worse in NGT-1-hour-high than in NGT-1-hour-normal. Dyslipidemia occurred in both the diabetes and pre-diabetes groups but not in either NGT group. One-hour glucose concentration ≥8.6 mmol/L showed substantial agreement for the two OGTTs (к=0.628).ConclusionsAlthough dyslipidemia did not occur in either NGT group, insulin resistance and beta-cell compromise were worse in NGT-1 hour-high. Subdividing the NGT group at a 1-hour glucose threshold of 8.6 mmol/L may stratify risk for diabetes in Africans.

Download Full-text

Population impact of increased body mass index and attenuated beta-cell function on worsening of glucose metabolism in subjects with normal glucose tolerance: a pilot study

Acta Diabetologica ◽

10.1007/s00592-013-0535-1 ◽

2013 ◽

Vol 51 (3) ◽

pp. 441-445 ◽

Cited By ~ 3

Author(s):

Keishi Yamauchi ◽

Rie Oka ◽

Kunimasa Yagi ◽

Kenshi Hayashi ◽

Masa-aki Kawashiri ◽

...

Keyword(s):

Body Mass Index ◽

Pilot Study ◽

Glucose Metabolism ◽

Glucose Tolerance ◽

Beta Cell ◽

Beta Cell Function ◽

Cell Function ◽

Normal Glucose Tolerance ◽

Population Impact ◽

Normal Glucose

Download Full-text

Four-Year Follow-Up of Glucose Tolerance and Beta-Cell Function in Nondiabetic Cystic Fibrosis Patients

Hormone Research ◽

10.1159/000184591 ◽

1995 ◽

Vol 44 (2) ◽

pp. 45-50 ◽

Cited By ~ 13

Author(s):

F. De Luca ◽

T. Arrigo ◽

A. Di Benedetto ◽

A. Tedeschi ◽

C. Sferlazzas ◽

...

Keyword(s):

Cystic Fibrosis ◽

Glucose Tolerance ◽

Beta Cell ◽

Beta Cell Function ◽

Cell Function

Download Full-text

A Systematic Review of Beta Cell Function in Adults of Black African Ethnicity

Journal of Diabetes Research ◽

10.1155/2019/7891359 ◽

2019 ◽

Vol 2019 ◽

pp. 1-17 ◽

Cited By ~ 1

Author(s):

M. Ladwa ◽

O. Hakim ◽

S. A. Amiel ◽

L. M. Goff

Keyword(s):

Insulin Secretion ◽

Glucose Tolerance ◽

Beta Cell ◽

Beta Cell Function ◽

Cell Function ◽

Normal Glucose Tolerance ◽

Qualitative Synthesis ◽

Intravenous Glucose ◽

Black African

Background. Understanding ethnic differences in beta cell function has important implications for preventative and therapeutic strategies in populations at high risk of type 2 diabetes (T2D). The existing literature, largely drawn from work in children and adolescents, suggests that beta cell function in black African (BA) populations is upregulated when compared to white Europeans (WE). Methods. A systematic literature search was undertaken in June 2018 to identify comparative studies of beta cell function between adults (>age 18 years) of indigenous/diasporic BA and WE ethnicity. All categories of glucose tolerance and all methodologies of assessing beta cell function in vivo were included. Results. 41 studies were identified for inclusion into a qualitative synthesis. The majority were studies in African American populations (n=30) with normal glucose tolerance (NGT)/nondiabetes (n=25), using intravenous glucose stimulation techniques (n=27). There were fewer studies in populations defined as only impaired fasting glucose/impaired glucose tolerance (IFG/IGT) (n=3) or only T2D (n=3). Although BA broadly exhibited greater peripheral insulin responses than WE, the relatively small number of studies which measured C-peptide to differentiate between beta cell insulin secretion and hepatic insulin extraction (n=14) had highly variable findings. In exclusively IGT or T2D cohorts, beta cell insulin secretion was found to be lower in BA compared to WE. Conclusions. There is inconsistent evidence for upregulated beta cell function in BA adults, and they may in fact exhibit greater deficits in insulin secretory function as glucose intolerance develops.

Download Full-text

Glucose tolerance stages in Cystic Fibrosis are idenfied by a unique pattern of defects of Beta-cell function

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgaa932 ◽

2020 ◽

Author(s):

Claudia Piona ◽

Sonia Volpi ◽

Chiara Zusi ◽

Enza Mozzillo ◽

Antonella Tosco ◽

...

Keyword(s):

Cystic Fibrosis ◽

Insulin Sensitivity ◽

Glucose Tolerance ◽

Beta Cell ◽

Beta Cell Function ◽

Cell Function ◽

Insulin Clearance ◽

Glucose Regulation ◽

Unique Pattern ◽

Glucose Tolerance Status

Abstract Aim To assess the order of severity of the defects of three direct determinants of glucose regulation, i.e., beta-cell function, insulin clearance and insulin sensitivity, in patients with CF categorized according their glucose tolerance status, including early elevation of mid-OGTT glucose values (>140 and < 200 mg/dL), named AGT140. Methods Two hundred and thirty-two CF patients aged 10-25 underwent OGTT. Beta-cell function and insulin clearance were estimated by OGTT mathematical modelling and OGTT-derived biomarkers of insulin secretion and sensitivity were calculated. The association between five glucose tolerance stages [NGT, AGT140, Indeterminate glucose Tolerance (INDET), impaired glucose tolerance (IGT), Cystic fibrosis related diabetes (CFRD)] and glucometabolic variables was assessed with general linear model. Results Beta-cell function and insulin sensitivity progressively worsened across glucose tolerance stages (p<0.001) with AGT140 patients significantly differing from NGT (all p<0.01). AGT140 and INDET showed a degree of beta-cell dysfunction similar to IGT and CFRD, respectively (all p<0.01). Insulin clearance was not significantly associated with glucose tolerance stages (p=0.162). Each class of glucose tolerance was uniquely identified by a specific combination of defects of the direct determinants of glucose regulation. Conclusions In CF patients each of the five glucose tolerance stages shows a unique pattern of defects of the direct determinants of glucose regulation, with AGT140 patients significantly differing from NGT and being similar to IGT. These findings suggest to recognize AGT 140 as a distinct glucose tolerance class and to reconsider the grade of glucometabolic deterioration across glucose tolerance stages in CF.

Download Full-text