scholarly journals Hypoglycemia and Islet Dysfunction Following Oral Glucose Tolerance Testing in Pancreatic-Insufficient Cystic Fibrosis

2020 ◽  
Vol 105 (10) ◽  
pp. 3179-3189
Author(s):  
Marissa J Kilberg ◽  
Clea Harris ◽  
Saba Sheikh ◽  
Darko Stefanovski ◽  
Marina Cuchel ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Insulin Secretion ◽  
Glucose Tolerance ◽  
Early Phase ◽  
Oral Glucose ◽  
Oral Glucose Tolerance ◽  
Insulin Effect ◽  
Secretory Rate ◽  
C Peptide ◽  
Islet Dysfunction

Abstract Context Oral glucose tolerance test (OGTT)-related hypoglycemia is common in pancreatic-insufficient cystic fibrosis (PI-CF), but its mechanistic underpinnings are yet to be established. Objective To delineate the mechanism(s) underlying OGTT-related hypoglycemia. Design and Setting We performed 180-minute OGTTs with frequent blood sampling in adolescents and young adults with PI-CF and compared results with those from a historical healthy control group. Hypoglycemia (Hypo[+]) was defined as plasma glucose <65 mg/dL. We hypothesized that CF-Hypo[+] would demonstrate impaired early phase insulin secretion and persistent late insulin effect compared with control-Hypo[+], and explored the contextual counterregulatory response. Main Outcome Measure OGTT 1-hour and nadir glucose, insulin, C-peptide, and insulin secretory rate (ISR) incremental areas under the curve (AUC) between 0 and 30 minutes (early) and between 120 and 180 minutes (late), and Δglucagon120-180min and Δfree fatty acids (FFAs)120-180min were compared between individuals with CF and control participants with Hypo[+]. Results Hypoglycemia occurred in 15/23 (65%) patients with CF (43% female, aged 24.8 [14.6-30.6] years) and 8/15 (55%) control participants (33% female, aged 26 [21-38] years). The CF-Hypo[+] group versus the control-Hypo[+] group had higher 1-hour glucose (197 ± 49 vs 139 ± 53 mg/dL; P = 0.05) and lower nadir glucose levels (48 ± 7 vs 59 ± 4 mg/dL; P < 0.01), while insulin, C-peptide, and ISR-AUC0-30 min results were lower and insulin and C-peptide, and AUC120-180min results were higher (P < 0.05). Individuals with CF-Hypo[+] had lower Δglucagon120-180min and ΔFFA120-180min compared with the control-Hypo[+] group (P < 0.01). Conclusions OGTT-related hypoglycemia in PI-CF is associated with elevated 1-hour glucose, impaired early phase insulin secretion, higher late insulin exposure, and less increase in glucagon and FFAs. These data suggest that hypoglycemia in CF is a manifestation of islet dysfunction including an impaired counterregulatory response.

scholarly journals The relationship between fasting hyperglycemia and insulin secretion in subjects with normal or impaired glucose tolerance

2008 ◽  
Vol 295 (2) ◽  
pp. E401-E406 ◽  
Author(s):  
Muhammad A. Abdul-Ghani ◽  
Masafumi Matsuda ◽  
Rucha Jani ◽  
Christopher P. Jenkinson ◽  
Dawn K. Coletta ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Glucose Tolerance ◽  
Impaired Glucose Tolerance ◽  
Plasma Glucose ◽  
Early Phase ◽  
Mexican Americans ◽  
Late Phase ◽  
Oral Glucose ◽  
C Peptide ◽  
The Relationship

To assess the relationship between the fasting plasma glucose (FPG) concentration and insulin secretion in normal glucose tolerance (NGT) and impaired glucose tolerance (IGT) subjects, 531 nondiabetic subjects with NGT ( n = 293) and IGT ( n = 238; 310 Japanese and 232 Mexican Americans) received an oral glucose tolerance test (OGTT) with measurement of plasma glucose, insulin, and C-peptide every 30 min. The insulin secretion rate was determined by plasma C-peptide deconvolution. Insulin sensitivity (Matsuda index) was measured from plasma insulin and glucose concentrations. The insulin secretion/insulin resistance (IS/IR) or disposition index was calculated as ΔISR/ΔG ÷ IR. As FPG increased in NGT subjects, the IS/IR index declined exponentially over the range of FPG from 70 to 125 mg/dl. The relationship between the IS/IR index and FPG was best fit with the equation: 28.8 exp(−0.036 FPG). For every 28 mg/dl increase in FPG, the IS/IR index declined by 63%. A similar relationship between IS/IR index and FPG was observed in IGT. However, the decay constant was lower than in NGT. The IS/IR index for early-phase insulin secretion (0–30 min) was correlated with the increase in FPG in both NGT and IGT ( r = −0.43, P < 0.0001 and r = −0.20, P = 0.001, respectively). However, the correlation between late-phase insulin secretion (60–120 min) and FPG was not significant. In conclusion, small increments in FPG, within the “normal” range, are associated with a marked decline in glucose-stimulated insulin secretion and the decrease in insulin secretion with increasing FPG is greater in subjects with NGT than IGT and primarily is due to a decline in early-phase insulin secretion.

scholarly journals Spontaneous hypoglycemia in patients with cystic fibrosis

2007 ◽  
Vol 156 (3) ◽  
pp. 369-376 ◽  
Author(s):  
A Battezzati ◽  
P M Battezzati ◽  
D Costantini ◽  
M Seia ◽  
L Zazzeron ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Insulin Secretion ◽  
Glucose Tolerance ◽  
Clinical Status ◽  
Class I ◽  
Oral Glucose ◽  
Anthropometric Parameters ◽  
C Peptide ◽  
Mutation Carriers ◽  
Reactive Hypoglycemia

Objective: Diabetes frequently complicates cystic fibrosis (CF) without fasting hyperglycemia or despite spontaneous hypoglycemia (anecdotally ascribed to malnutrition), whose prevalence, clinical meaning, and relationship with glucose tolerance and clinical/nutritional status were not previously investigated. The relationship of CF genotype with insulin secretion control is also unclear. Design and methods: A total of 129 CF patients without stable diabetes received 188 oral glucose tolerance tests. Distribution of fasting plasma glucose (FPG), glucose, insulin and C-peptide responses, clinical/nutritional variables, and their relationships were analyzed. Results: FPG < 60 mg/dl (3.3 mmo/l) was detected in 14% of studies and reactive hypoglycemia (PG < 50 mg/dl (2.8 mmo/l)) in 15%. OGTT-based diabetes frequency was similar in the lowest quartile (Q1) and Q2–3 for FPG (10 and 8%), with higher glucose increment and area under the curve in Q1. Insulin and C-peptide levels were similar among FPG quartiles. Class I cystic fibrosis transmembrane conductance regulator mutation carriers had higher insulin concentrations than class II, especially in Q1 for FPG. Age, sex, nutritional, and anthropometric parameters including fat and lean body mass were unrelated to FPG. Lower FPG was associated with more frequent hospitalization rates (P = 0.002) and lower Shwachman scores (P = 0.041). Steroids weaning was accurately evaluated but then excluded as a possible cause of hypoglycemia. Conclusions/interpretation: Fasting asymptomatic hypoglycemia is frequent and possibly related to inappropriate insulin secretion control in class I mutation carriers. Low FPG does not exclude impaired glucose tolerance (IGT) and diabetes in CF and reflects worse clinical status.

scholarly journals MON-660 Hypoglycemia Following OGTT Is More Frequent and Pronounced in CF Compared with Controls

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Clea D Harris ◽  
Marissa J Kilberg ◽  
Saba Sheikh ◽  
Darko Stefanovski ◽  
Marina Cuchel ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Insulin Secretion ◽  
Glucose Tolerance ◽  
Early Phase ◽  
Tolerance Test ◽  
Normal Glucose Tolerance ◽  
Oral Glucose ◽  
Reactive Hypoglycemia ◽  
Glucose Dysregulation ◽  
Student’S T

Abstract Glucose homeostasis is often abnormal in people with pancreatic insufficient cystic fibrosis (PI-CF). This dysfunction is viewed on a continuum from “normal” glucose tolerance to cystic fibrosis-related diabetes (CFRD), and may also include postprandial and oral glucose tolerance test (OGTT)-related hypoglycemia. This study aimed to delineate the mechanism(s) underlying OGTT-related hypoglycemia. We compared extended OGTT with frequent blood sampling of glucose and insulin in adolescents and young adults with PI-CF [CF(+)] to historical data from a healthy cohort [CF(-)]. We hypothesized that the subset of CF(+) with hypoglycemia would demonstrate 1-hour glucose ≥ 155 mg/dL and impaired early phase insulin secretion (insulin secretion within first 30 min of OGTT). Hypoglycemia [hypo(+)] was defined as plasma glucose &lt;65 mg/dL and was used to assign subjects to exposure groups. We restricted analyses to 180 minutes given available control data. Glucose and insulin incremental areas under the curve (Glc-AUC; Ins-AUC) for 30-minute intervals were calculated. One-hour glucose, nadir glucose, Glc-AUC0-30, and Ins-AUC0-30 and were compared between CF(+) and CF(-) subjects using Student’s t-test or Wilcoxon Rank Sum depending upon normality. Participants were 60.5% male, age: 25.4±4.8 years, with BMI-Z: 0.06±0.96kg/m2 [no differences for CF(+) vs CF(-)]. FEV1%-predicted for CF(+) was 83±21. 69.6% of CF(+) participants self-reported prior episodes of hypoglycemia, 68.7% of whom reported confirmation via glucometer. Hypoglycemia occurred by 180 minutes [hypo(+)] in 15/23 (65%) CF(+) and 5/15 (33.3%) CF(-) subjects (p=0.028). For hypo(+), nadir glucose occurred on average at 180 minutes for both CF(+) and (-). Hypo(+) CF(+) had higher mean 1-hour glucose (197±49mg/dL vs 134±66mg/dL, p=0.035), lower mean glucose nadir (48±7mg/dL vs 61±4mg/dL, p&lt;0.01), and lower early-phase insulin secretion (Ins-AUC0-30: 263±168 versus 650±275 µU/mL, p&lt;0.01) than hypo(+) CF(-). There was no difference in Glc-AUC0-30 for hypo(+) CF(+) vs CF(-). Hypoglycemia is frequent in CF, and is associated with early glucose dysregulation (elevated 1-hour glucose) and compromised early-phase insulin secretion compared to controls with presumed non-pathologic reactive hypoglycemia. The mechanism of hypoglycemia in CF appears to be different than that seen in healthy individuals, and its association with progression to CFRD warrants further evaluation.

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