scholarly journals Natural history of glucose tolerance, beta-cell function and peripheral insulin sensitivity in cystic fibrosis patients with fasting euglycemia

2003 ◽  
Vol 149 (1) ◽  
pp. 53-59 ◽  
Author(s):  
F Lombardo ◽  
F De Luca ◽  
M Rosano ◽  
C Sferlazzas ◽  
C Lucanto ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Insulin Sensitivity ◽  
Natural History ◽  
Glucose Tolerance ◽  
Pancreatic Beta Cells ◽  
Cell Function ◽  
Glucose Levels ◽  
Peripheral Insulin Resistance ◽  
History Of ◽  
Over Time

OBJECTIVE: The loss of pancreatic beta-cells is thought to be one of the principal causes of diabetes mellitus (DM) in cystic fibrosis (CF), but the role of peripheral insulin resistance (IR) in the pathogenesis of DM in CF remains unclear. The aim of this study was to evaluate whether eventual changes of glucose tolerance (GT) over time were associated with modifications of insulin secretion or sensitivity. METHODS: Plasma glucose and insulin responses to an oral GT test (OGTT) were investigated and reinvestigated 13 Years later in 14 CF patients with initial and persistent fasting euglycemia and no history of insulin treatment. Insulin sensitivity (IS) at both tests was assessed on the basis of insulin and glucose levels both in the fasting state and during OGTTs. RESULTS: From the 1st to the 2nd OGTT: (a) the prevalence of DM responses significantly increased; (b) the areas beneath the respective glucose and insulin curves significantly increased and decreased respectively; (c) IR and IS indices decreased and increased respectively, even in the patients who developed DM; (d) pulmonary function significantly worsened in the entire series, especially in the patients who developed DM. CONCLUSIONS: (i) the natural history of glyco-metabolic status in CF is characterized by deteriorating GT over time; (ii) insulinopenia plays a prominent role in the pathogenesis of GT worsening; (iii) IR does not play any significant part in the pathogenesis of DM development; (iv) deterioration of lung function tests is more severe in the subjects who develop DM over time.

Effects of pioglitazone and metformin on β-cell function in nondiabetic subjects at high risk for type 2 diabetes

2007 ◽  
Vol 292 (1) ◽  
pp. E359-E365 ◽  
Author(s):  
Neda Rasouli ◽  
Philip A Kern ◽  
E. Albert Reece ◽  
Steven C. Elbein
Keyword(s):  
At Risk ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Cell Function ◽  
Glucose Disposal ◽  
Β Cell ◽  
Intravenous Glucose ◽  
Glucose Levels ◽  
Β Cell Function

Thiazolidinediones (TZDs) and metformin decreased the incidence of diabetes in subjects at risk for developing diabetes and improved peripheral or hepatic insulin sensitivity, respectively. Whether they also directly improved β-cell function is not clear. In vitro studies showed improved β-cell function in response to TZDs and metformin; however, the effects of TZDs or metformin on β-cell function in humans are still uncertain. We hypothesized that both TZDs and metformin directly affect β-cell function. We evaluated β-cell function and insulin sensitivity (SI) in subjects with impaired glucose tolerance or a history of gestational diabetes using oral and intravenous glucose tolerance tests in addition to the glucose-potentiated arginine stimulation test. In contrast to metformin, pioglitazone improved SI, glucose tolerance, and insulin-independent glucose disposal [glucose effectiveness (SG)]. Neither pioglitazone nor metformin significantly improved β-cell compensation for insulin resistance [disposition index (DI)], but the change in DI significantly correlated with baseline SI. Insulin secretion in response to arginine at maximally potentiating glucose levels (AIRmax) tended to increase after metformin and to decrease after pioglitazone; however, when adjusted for SI, the changes were not significant. Our results demonstrate that, in nondiabetic subjects at risk for diabetes, pioglitazone, but not metformin, significantly improved glucose tolerance by improving SI and SG. We did not find any evidence that either pioglitazone or metformin improved β-cell function. Improved β-cell compensation was observed primarily in the subgroup of subjects that had the lowest SI at baseline.

Identifying glucose thresholds for incident diabetes by physiological analysis: a mathematical solution

2015 ◽  
Vol 308 (7) ◽  
pp. R590-R596 ◽  
Author(s):  
Ele Ferrannini ◽  
Maria Laura Manca
Keyword(s):  
Insulin Sensitivity ◽  
Confidence Interval ◽  
Glucose Tolerance ◽  
Odds Ratio ◽  
Cell Function ◽  
Oral Glucose ◽  
Oral Glucose Tolerance ◽  
Β Cell ◽  
Glucose Levels ◽  
Β Cell Function

Plasma glucose thresholds for diagnosis of type 2 diabetes are currently based on outcome data (risk of retinopathy), an inherently ill-conditioned approach. A radically different approach is to consider the mechanisms that control plasma glucose, rather than its relation to an outcome. We developed a constraint optimization algorithm to find the minimal glucose levels associated with the maximized combination of insulin sensitivity and β-cell function, the two main mechanisms of glucose homeostasis. We used a training cohort of 1,474 subjects (22% prediabetic, 7.7% diabetic) in whom insulin sensitivity was measured by the clamp technique and β-cell function was determined by mathematical modeling of an oral glucose tolerance test. Optimized fasting glucose levels were ≤87 and ≤89 mg/dl in ≤45-yr-old women and men, respectively, and ≤92 and ≤95 mg/dl in >45-yr-old women and men, respectively; the corresponding optimized 2-h glucose levels were ≤96, ≤98, ≤103, and ≤105 mg/dl. These thresholds were validated in three prospective cohorts of nondiabetic subjects (Relationship Between Insulin Sensitivity and Cardiovascular Disease Study, Botnia Study, and Mexico City Diabetes Study) with baseline and follow-up oral glucose tolerance tests. Of 5,593 participants, 452 progressed to diabetes. Similarly, in the three cohorts, subjects with glucose levels above the estimated thresholds had an odds ratio of 3.74 (95% confidence interval = 2.64–5.48) of progressing, substantially higher than the risk carried by baseline conventionally defined prediabetes [odds ratio = 2.32 (95% confidence interval = 1.91–2.81)]. The concept that optimization of glucose concentrations by direct measures of insulin sensitivity and β-cell function identifies gender- and age-specific thresholds that bear on disease progression is proven in a physiologically sound, quantifiable manner.

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

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.

scholarly journals Prior lactation reduces future diabetic risk through sustained postweaning effects on insulin sensitivity

2017 ◽  
Vol 312 (3) ◽  
pp. E215-E223 ◽  
Author(s):  
Harpreet Bajaj ◽  
Chang Ye ◽  
Anthony J. Hanley ◽  
Philip W. Connelly ◽  
Mathew Sermer ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Cell Function ◽  
Infant Nutrition ◽  
Oral Glucose ◽  
Β Cell ◽  
Full Spectrum ◽  
Beneficial Effects ◽  
Β Cell Function ◽  
History Of

Breastfeeding for ≥12 mo is recommended for optimal infant nutrition but may hold maternal benefits as well. Indeed, lactation has been associated with lower long-term risk of diabetes in the mother, but the mechanism by which it imparts sustained postweaning effects on glucose tolerance remains unclear. In this context, we postulated that lactation could potentially induce postweaning beneficial effects on glucose tolerance by modifying the natural history of insulin sensitivity and/or pancreatic β-cell function over time. Thus, in this study, we evaluated the relationships between duration of lactation [≤3 mo ( n = 70), 3–12 mo ( n = 140), and ≥12 mo ( n = 120)] and trajectories of insulin sensitivity/resistance, β-cell function, and glycemia over the first 3 yr postpartum in a cohort of 330 women comprising the full spectrum of glucose tolerance in pregnancy, who underwent serial metabolic characterization, including oral glucose tolerance tests, at 3 mo, 1 yr, and 3 yr postpartum. The prevalence of dysglycemia (pre-diabetes/diabetes) at 3 yr postpartum was lower in women who breastfed for ≥12 mo (12.5%) than in those who breastfed for ≤3 mo (21.4%) or for 3–12 mo (25.7%)(overall P = 0.028). On logistic regression analysis, lactation for ≥12 mo independently predicted a lower likelihood of prediabetes/diabetes at 3 yr postpartum (OR = 0.37, 95% CI 0.18–0.78, P = 0.009). Notably, lactation for ≥12 mo predicted lesser worsening of insulin sensitivity/resistance ( P < 0.0001), fasting glucose ( P < 0.0001), and 2-h glucose ( P = 0.011) over 3 yr compared with lactation ≤3 mo but no differences in β-cell function ( P ≥ 0.37). It has thus emerged that adherence to current breastfeeding recommendations reduces future diabetic risk through sustained postweaning effects on insulin sensitivity/resistance but not β-cell function.

No changes of insulin sensitivity in cystic fibrosis patients with different degrees of glucose tolerance: an epidemiological and longitudinal study

1994 ◽  
Vol 130 (3) ◽  
pp. 253-258 ◽  
Author(s):  
Domenico Cucinotta ◽  
Filippo De Luca ◽  
Alfonso Gigante ◽  
Teresa Arrigo ◽  
Antonino Di Benedetto ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Insulin Secretion ◽  
Longitudinal Study ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Clinical Status ◽  
Fasting Blood Glucose ◽  
Oral Glucose ◽  
Insulin Responses ◽  
Over Time

Cucinotta D, De Luca F, Gigante A, Arrigo T, Di Benedetto A, Tedeschi A, Lombardo F, Romano G, Sferlazzas C. No changes of insulin sensitivity in cystic fibrosis patients with different degrees of glucose tolerance: an epidemiological and longitudinal study. Eur J Endocrinol 1994;130:253–8. ISSN 0804–4643 Plasma glucose and insulin responses to oral glucose and insulin sensitivity by the euglycemic hyperinsulinemic clamp technique were investigated in 30 cystic fibrosis patients with normal fasting blood glucose levels and normal (N = 12), impaired (N = 12) or diabetic (N = 6) glucose tolerance, and in 12 control subjects. In a subgroup of 10 cystic fibrosis patients with non-diabetic glucose tolerance both oral glucose tolerance test and clamp were performed again 48–52 months later. Following oral glucose, glycemic responses were higher in cystic fibrosis patients than in controls, whereas insulin responses were reduced significantly only in the patients with diabetic glucose tolerance. Insulin sensitivity did not differ significantly in the patient subgroups with different degrees of glucose tolerance and in controls. In the 10 patients who underwent a 4-year follow-up, insulin responses to oral glucose decreased significantly, whilst insulin sensitivity did not change substantially. Insulin sensitivity persisted unmodified even in the patients with deteriorating glucose tolerance. No correlations were observed between metabolic data and clinical status of patients. In conclusion, in cystic fibrosis subjects with fasting euglycemia and different degrees of glucose tolerance: (i) insulin sensitivity is not impaired; (ii) eventual changes of glucose tolerance over time are not associated with modifications of insulin sensitivity; (iii) insulin secretion deteriorates over time even in the patients with stable glucose tolerance; (iv) eventual deterioration of both glucose tolerance and insulin secretion is not linked to a worsening of either nutritional or clinical parameters. F De Luca, Istituto di Clinica Pediatrica, Policlinico Universitario, 98100 Messina, Italy

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