Effects of acarbose in beta-thalassaemia major patients with normal glucose tolerance and hyperinsulinism

The pathogenesis of diabetes in thalassaemia is complex and multifactorial. Understanding the sequence of abnormalities in the progression from normal glucose tolerance to impaired glucose tolerance may help in the formulation of ways to intervene in this process. In our study, we assessed the effects of acarbose, an alpha-glucosidase inhibitor, in five young adult thalassaemic patients with hyperinsulinism and normal oral glucose tolerance test (OGTT). A decrease of fasting insulin levels, insulin peak and area under the curve (AUC) after OGTT, were observed in thalassaemic patients receiving acarbose therapy. These values remained unchanged in an untreated group of eight thalassaemic patients. We believe that acarbose may have a potential role in the treatment of abnormalities of glucose homeostasis and insulin release.     

Type 2 diabetes mellitus in African-American adolescents: impaired beta-cell function in the face of severe insulin resistance

We have previously demonstrated abnormalities in insulin secretion in adolescents with type 2 diabetes mellitus (DM2) in response to the mixed meal test and to glucagon. In order to further assess beta-cell function in DM2, we measured insulin and C-peptide responses to oral glucose in adolescents with DM2 in comparison to non-diabetic obese and lean adolescents. We studied 20 patients with DM2, 25 obese adolescents with matching body mass index (BMI) (33.8 +/- 1.4 vs 34.3 +/- 1.0 kg/m2), and 12 non-obese control adolescents (BMI 22.6 +/- 0.6 kg/m2). Mean age, sex and sexual maturation did not differ between the three groups. All adolescents with DM2 had negative islet cell antibodies (ICA); five patients were on diet and 15 on insulin treatment. Fasting lipid profiles were determined in all participants. Plasma glucose and serum C-peptide and insulin levels were measured at 0, 30, 60, 90, and 120 min after an oral glucose load. The C-peptide increment (deltaCP) was calculated as peak minus fasting C-peptide. Area under the curve (AUC) was estimated using the trapezoid method. Insulin resistance was estimated using the HOMA model (HOMA-IR). The first phase of insulin secretion (PH1) was computed using a previously published formula. Serum triglyceride levels were significantly higher in the patients with DM2 compared to the non-obese controls (1.4 +/- 0.1 vs 0.9 +/- 0.1 mmol/l; p = 0.02). Plasma glucose AUC was greater in the patients with DM2 compared to the obese and non-obese control groups (1,660 +/- 130 vs 717 +/- 17 vs 647 +/- 14 mmol/l x min; p < 0.0001). ACP was lower in adolescents with DM2 than in obese and non-obese adolescents (761 +/- 132 vs 1,721 +/- 165 vs 1,225 +/- 165 pmol/l; p < 0.001). Insulin AUC was lower in the patients with DM2 compared to obese controls (888 +/- 206 vs 1,606 +/- 166 pmol/l x h; p = 0.009), but comparable to that of the non-obese controls (888 +/- 206 vs 852 +/- 222 pmol/l x h; p = 0.9). Insulin AUC was also higher in the obese than in the non-obese group (p = 0.05). PH1 was significantly higher in the obese group compared to the patients with DM2 as well as to the non-obese controls (2,614 +/- 2,47.9 vs 929.6 +/- 403.5 vs 1,946 +/- 300.6 pmol/l, respectively; p = 0.001). PH1 was also higher in the non-obese controls than in the patients with DM2 (p = 0.05). HOMA-IR was three-fold higher in the patients with DM2 than in the BMI-matched obese group, and five-fold higher than in the lean controls (14.3 +/- 1.2 vs 5.4 +/- 0.8 vs 2.9 +/- 0.4; p = 0.0002). Adolescents with DM2 have dyslipidemia, a significant cardiovascular risk factor. Decreased beta-cell function is characteristic of adolescents with DM2 in the presence of severe insulin resistance.     

Prevalence of impaired glucose metabolism in β-thalassemic children receiving hypertransfusions with a suboptimal dosage of iron-chelating therapy

A cross-sectional study of impaired glucose metabolism was carried out in 48 beta-thalassemic patients receiving hypertransfusions. An oral glucose tolerance test (OGTT) was performed using the method and criteria of the American Diabetes Association (ADA). Diabetes mellitus was diagnosed in two patients, and impaired glucose tolerance was found in four patients, giving a prevalence of impaired glucose metabolism of 12.5% in our patient population. The significant clinical characteristics associated with the diagnosis of impaired glucose metabolism were wasting (-2.15/-0.86 SDS, p = 0.025), stunting (-2.69/-1.22 SDS, p = 0.03), higher ferritin levels (8679/4710 mug/L, p = 0.005), splenectomy (50/9.5%, p = 0.012), and lower area under curve (AUC) of insulin secretion after OGTT (40.0/77.7, p = 0.002). The significant decrease of AUC insulin in thalassemic patients with an impaired glucose tolerance test suggests that the pathogenesis may originate from pancreatic beta-cell damage rather than from insulin resistance. In conclusion, the prevalence of impaired glucose tolerance in our population of thalassemic patients receiving hypertransfusions with suboptimal iron chelating therapy was 12.5%. The clinical characteristics of thalassemic patients who developed impaired glucose tolerance were wasting, stunting, higher ferritin levels, splenectomy, and lower AUC insulin.     

Pancreatic alpha and beta cell functions in cystic fibrosis.

Insulin and glucagon secretions were studied during oral glucose tolerance testing and arginine infusion in 13 patients with cystic fibrosis. Two groups of patients were identified; Group I (N=6) whose OGTT was entirely normal and Group II (N=7) who had some abnormality in glucose during OGTT. In each group basal glucagon concentrations were normal and supressed appropriately (p less than 0.05) after glucose; insulin responses were attenuated and the peak responses delayed. During arginine stimulation, insulin secretion was impaired in each group. However, glucagon secretion was diminished only in Group II. Thus, insulinopenia was found in both groups and hyperglucagonemia was not found as a contributory factor to the hyperglycemia in Group II.     

The abnormalities of carbohydrate metabolism in Turner syndrome: analysis of risk factors associated with impaired glucose tolerance

An oral glucose tolerance test (OGTT) was performed in 103 patients with Turner syndrome (TS) who had normal fasting and postprandial glucose levels. The plasma glucose, insulin, C-peptide and proinsulin levels were measured every 30 min during the test. Using a homeostatic model assessment (HOMA) and a quantitative insulin sensitivity check index (QUICKI), the insulin resistance in TS patients was investigated. Diabetes mellitus and impaired glucose tolerance (IGT) were newly diagnosed in two and 18 patients respectively. There was a significant increase in mean plasma glucose, insulin, C-peptide and proinsulin reponse during an OGTT in the IGT group in contrast to the normal glucose tolerance (NGT) group ( P <0.05). There was a significant decrease in the quantitative insulin sensitivity check index (QUICKI) in the IGT group in contrast to the NGT group ( P <0.05). The fasting insulin and triglyceride levels strongly predicted the 2 h glucose level during the OGTT ( P <0.05). Conclusion:The oral glucose tolerance test is superior to the fasting and postprandial plasma glucose test for the early detection of abnormalities of carbohydrate metabolism in patients with Turner syndrome.     

Hyperglycemia and hypoinsulinemia in patients with Fanconi-Bickel syndrome

Fanconi-Bickel syndrome (FBS) is a rare autosomal recessive disorder characterized by the combination of hepatorenal glycogen accumulation and Fanconi-type nephropathy. Mutations in GLUT2, the gene for facilitative glucose transporter protein 2 (GLUT2), cause FBS. AIM: To evaluate glucose and insulin responses to oral glucose load in patients with FBS. METHODS: Ten children (7.3 +/- 4.8 years) diagnosed with FBS in early infancy underwent a standard oral glucose tolerance test (OGTT); plasma glucose (PG) and serum insulin concentrations were measured at 30-min intervals for 2 hours. HbA1c, insulin-like growth factor-I, and fasting lipid profiles were also measured. RESULTS: Mean fasting and 2-h PG concentrations were 3.8 +/- 0.9 mmol/l and 8.6 +/- 3.0 mmol/1, respectively. 2-hour PG levels were above 11.1 mmol/l in two patients (20%) and between 7.75 and 11.1 mmol/ in four patients (40%). HbA1c was normal in all the patients with a mean of 5.4 +/- 0.3%. Mean fasting and peak serum insulin levels were 8.7 +/- 0.8 pmol/ and 98.6 +/- 43.0 pmol/l, respectively, and did not differ between the patients with normal and abnormal OGTT. Patients with abnormal OGTT were younger (4.8 +/- 3.2 vs 11.0 +/- 4.8 yr; p = 0.04). Fasting PG increased with age (r = 0.80, p < 0.01). Total and LDL cholesterol as well as triglyceride concentrations were elevated. CONCLUSIONS: Most but not all patients with FBS have impaired glucose tolerance/diabetes range hyperglycemia after OGTT while maintaining normal HbA1c. Patients with FBS are relatively hypoinsulinemic. Both fasting hypoglycemia and post-OGTT hyperglycemia seem to improve with age.     

Evaluation of growth hormone in thalassaemic boys with failed puberty: Spontaneous versus provocative test

Growth hormone (GH) secretion was determined by evaluating ultradian GH profiles for 12 h and GH responses to insulin stimulated hypoglycaemia (ITT) in 28 stunted boys with -thalassaemia major aged 15.2–17.4 years, who presented with pubertal failure (FP). Healthy non thalassaemia prepubertal boys (n=10) aged 7.5–8.8 years, were studied as controls. All patients had normal responses to ITT with peak GH levels 15 mU/l. Basal GH concentrations (mean±sem) (1.65±0.03 mU/l vs 2.58±0.27 mU/l;P<0.05) and the stimulated GH responses (peak GH=15.4±0.20 mU/l vs 21.08±0.78 mU/l;P<0.001) were significantly lower in the patients with failed puberty than in the controls, indicating that the FP patients had diminished GH reserve and secretory capacity. Moreover, all the GH peak parameters including the maximum spontaneous concentrations (MX-GH) and the area under the GH curve (AUC) were significantly lower in the thalassaemic patients than in the controls (MX-GH=5.2±0.21 mU/l vs 20.42±0.14 mU/l;P<0.001; AUCb=421.22±4.31 mU/l vs 712.20±3.42 mU/l;P<0.001). These observations suggest that the thalassaemic patients had endogenous neurosecretory GH deficiency (GHND). Priming with sex steroid did not cause any improvement in the spontaneous or stimulated GH secretory patterns in thalassaemic patients. It was noteworthy that in neither the patients nor the control subjects, was there a significant correlation between the maximum stimulated and the MX-GH concentrations. These data suggest that the provocative ITT underestimates spontaneous GH secretion and that measurement of spontaneous GH secretion was a more reliable method for identifying patients with GH insufficiency than the ITT.     

Beta-cell function assessed by plasma C-peptide evaluation in diabetic thalassaemic patients

In order to investigate the pancreatic function in patients with thalassaemia major, plasma glucose and immunoreactive C-peptide levels were determined in 9 diabetic thalassaemic patients and in 7 controls after arginine infusion. Mean basal and peak values and C-peptide areas in thalassaemic patients did not differ significantly from those of the controls. However, in the thalassaemic group there was a greater variation in values, since pancreatic beta-cell function was found either normal, reduced or increased. These findings could suggest that different factors may lead to diabetes which complicates thalassaemia, i.e. insulin-resistance, probably due to liver damage subsequent to iron deposition and infectious hepatitis, and insulinopenia, probably due to beta-cell lesion following iron storage in the pancreas.     

Reduced pancreatic insulin release and reduced peripheral insulin sensitivity contribute to hyperglycaemia in cystic fibrosis

Traditional opinion holds that patients with cystic fibrosis (CF) develop impaired glucose tolerance or diabetes due to insulinopenia caused by fibrosis of the pancreas. However, studies on the dynamics of insulin secretion and peripheral insulin action have yielded confliciting results. We studied 18 patients with CF (9 , 9 , age 15–29 years) and 17 healthy control subjects (8 , 9 , 20–32 years). Oral glucose tolerance tests and combined i.v.-glucose-tolbutamide-tests were performed on separate days in fasting subjects. Bergman's Minimal Model was used to quantitate both peripheral insulin sensitivity (S_I) and insulin-independent glucose disposal (glucose effectiveness; S_G). Based on National Diabetes Data Group criteria, 4 patients were classified as diabetic 922%; CF-DM), 3 patients (17%) had impaired glucose tolerance (CF-IGT) while glucose metabolism was normal in 11 patients (61%; CF-NGT). Irrespective of the degree of glucose tolerance, the insulin response to oral glucose was not reduced but delayed, up to 60 min in the CF-IGT/DM group. First-phase insulin release (0–10 min) after i.v.-glucose was significantly lower in CF patients (29% of healthy controls;P<0.0001), with no difference between the CF-NGT and CF-IGT/DM groups. Insulin release following tolbutamide injection was only marginally reduced in CF patients (64% of controls). In contrast, S_I was significantly reduced in the subgroup of CF patients with abnormal glucose metabolism (CF-IGT/DM: 0.97±0.16·10^–4 l/min/pmol; control group: 1.95±0.25;P<0.05).Conclusion The early insulin release is reduced in response to i.v.-glucose, while in the oral glucose tolerance test, insulin secretion is quantitatively preserved, but delayed. Reduced peripheral insulin sensitivity is a major factor for impaired glucose tolerance and diabetes mellitus in CF patients.     

Spontaneous and provoked growth hormone (GH) secretion and insulin-like growth factor I (IGF-I) concentration in patients with beta thalassaemia and delayed growth

Growth retardation in children with thalassaemia major is multifactorial. We studied the growth hormone (GH) response to provocation by clonidine and glucagon, measured the circulating concentrations of insulin, insulin-like growth factor-I (IGF-I), IGF-binding protein-3 (IGFBP3), and ferritin, and evaluated the spontaneous nocturnal (12 h) GH secretion in prepubertal patients with thalassaemia and age-matched children with constitutional short stature (CSS) (height SDS < -2, but normal GH response to provocation). The anatomy of the hypothalamic pituitary area was studied in patients with abnormal GH secretion using MRI scanning. Children with thalassaemia had significantly lower peak GH response to provocation by clonidine and glucagon (8.8 +/- 2.3 micrograms/l and 8.2 +/- 3.1 micrograms/l respectively) than did controls (17.6 +/- 2.7 micrograms/l and 15.7 +/- 3.7 micrograms/l respectively). They had significantly decreased circulating concentrations of IGF-I and IGFBP3 (68.5 +/- 19 ng/ml and 1.22 +/- 0.27 mg/l respectively) compared to controls (153 +/- 42 ng/ml and 2.16 +/- 0.37 mg/l respectively). Seven of the thalassaemic children had a GH peak response of < 7 micrograms/l after provocation. Those with a normal GH response after provocation also had significantly lower IGF-I and IGFBP3 concentrations than controls. Analysis of their spontaneous nocturnal GH secretion revealed lower mean (2.9 +/- 1.77 micrograms/l) and integrated (2.53 +/- 1.6 micrograms/l) concentrations compared to controls (4.9 +/- 0.29 micrograms/l and 5.6 +/- 0.52 micrograms/l respectively). Five of them had mean nocturnal GH concentration < 2 micrograms/l and four had maximum nocturnal peak below 10 micrograms/l. These data denoted defective spontaneous GH secretion in some of these patients. MRI studies revealed complete empty sella (n = 2), marked diminution of the pituitary size (n = 4), thinning of the pituitary stalk (n = 3) with its posterior displacement (n = 2), and evidence of iron deposition in the pituitary gland and midbrain (n = 7) in those patients with defective GH secretion (n = 9). Serum ferritin concentration was correlated significantly with the circulating IGF-I (r = -0.47, p < 0.01) and IGFBP3 (r = -0.43, p < 0.01) concentrations. These data prove a high prevalence of defective GH secretion in thalassaemic children associated with structural abnormality of their pituitary gland.     

Intravenous glucose tolerance and plasma insulin response in children with homozygous β-thalassaemia

ABSTRACT. Glucose tolerance and insulin secretion were studied after intravenous glucose load in 10 normal and 27 children with homozygous β-thalassaemia of whom 11 received 5–20 units of blood (1.25–5g total iron) and 16 received 50–60 blood units (12.5–40g total iron). Fasting blood glucose and insulin levels were similar in normal and thalassaemic children. Differences were found at 10 and 20 minutes of intravenous glucose administration both in glucose blood levels. (which were considerably higher) and insulin levels (which were significantly lower), in thalassaemic patients compared to normal children. Evidence of depression of pancreatic function was found in three out of 11 patients, with low and in three out of 16 patients with severe iron load. These findings suggest that in thalassaemia pancreatic impairment is not always directly related to the degree of iron overload.     

Repetitiveness of the oral glucose tolerance test in children and adolescents

BACKGROUNDData regarding the most suitable diagnostic method for the diagnosis of glucose impairment in asymptomatic children and adolescents are inconclusive. Furthermore, limited data are available on the reproducibility of the oral glucose tolerance test (OGTT) in children and adolescents who are obese (OB).AIMTo investigate the usefulness of the OGTT as a screening method for glucose dysregulation in children and adolescents.METHODSEighty-one children and adolescents, 41 females, either overweight (OW), OB or normal weight (NW) but with a strong positive family history of type 2 diabetes mellitus (T2DM), were enrolled in the present observational study from the Outpatient Clinic of Paediatric Endocrinology of the University Hospital of Patras in Greece. One or two 3-h OGTTs were performed and glucose, insulin and C-peptide concentrations were measured at several time points (t = 0 min, t = 15 min, t = 30 min, t = 60 min, t = 90 min, t = 120 min, t = 180 min).RESULTSGood repetitiveness was observed in the OGTT response with regard to T2DM, while low repetitiveness was noted in the OGTT response with regard to impaired glucose tolerance (IGT) and no repetitiveness with regard to impaired fasting glucose (IFG). In addition, no concordance was observed between IFG and IGT. During the 1^st and 2^nd OGTTs, no significant difference was found in the glucose concentrations between NW, OW and OB patients, whereas insulin and C-peptide concentrations were higher in OW and OB compared to NW patients at several time points during the OGTTs. Also, OW and OB patients showed a worsening insulin and C-peptide response during the 2^nd OGTT as compared to the 1^st OGTT.CONCLUSIONIn mild or moderate disorders of glucose metabolism, such as IFG and IGT, a diagnosis may not be reached using only one OGTT, and a second test or additional investigations may be needed. When glucose metabolism is profoundly impaired, as in T2DM, one OGTT is probably more reliable and adequate for establishing the diagnosis. Excessive weight and/or a positive family history of T2DM possibly affect the insulin and C-peptide response in the OGTT from a young age.     

Insulin resistance and beta cell function in chronically transfused patients of thalassemia major

OBJECTIVE: To assess the glycometabolic function in chronically transfused patients of beta- thalassemia major in terms of glucose tolerance, insulin secretion, insulin resistance index, and beta cell function index and to determine their relationship with clinical and biochemical profile. METHODS: 30 homozygous thalassemia major children (aged 8-15 years) receiving regular blood transfusion and 10 age and sex matched normal children attending a tertiary level hospital were subjected to glucose tolerance test, estimation of fasting plasma insulin level, insulin resistance index and beta cell function index. Liver enzymes, liver size and indicators of iron overload (serum ferritin, total units of blood transfused, splenic size) were recorded. RESULTS: There was no diabetes mellitus or impaired glucose tolerance test in either the cases or the controls. Fasting plasma insulin levels were significantly higher in cases than controls (P = 0.004), and correlated well with indicators of iron overload like total units of blood transfused (r = 0.41, P = 0.03), serum ferritin (r = 0.38, P = 0.038) and splenic size (r = 0.43, P = 0.03). Insulin resistance was higher in cases compared to controls (P = 0.01). It correlated well with age (r = 0.56, P = 0.006), fasting blood glucose (r = 0.8, P = 0.003), fasting plasma insulin (r = 0.95, P = 0.00001), total units of blood transfused (r = 0.52, P = 0.005), serum ferritin (r = 0.4, P = 0.02) and splenomegaly (r = 0.51, P = 0.004). Insulin resistance was higher in patients not on chelation therapy compared with those on chelation therapy (P = 0.003). The beta cell function index was higher in cases compared to the controls, but not of statistic significance (P = 0.077). It did not correlate well with total amount of blood transfused (r = -0.32, P = 0.08), serum ferritin (r = -0.138, P = 0.46), spleen size (r = 0.16, P = 0.36), or chelation therapy (P = 0.98). CONCLUSION: Diabetes mellitus or impaired glucose was not seen in chronically transfused patients of thalassemia major (between 8 and 15 years of age), in our study. Insulin resistance, compensated by hyperinsulinemia, sets in early even before the onset of frank diabetes mellitus and correlated well with age, chelation therapy and indicators of iron overload like total units of blood transfused, splenomegaly and serum ferritin.     

Slowly deteriorating insulin secretion and C-peptide production characterizes diabetes mellitus in infantile cystinosis

Infantile cystinosis, a rare lysosomal storage disease of cystine, leads to Fanconi syndrome and end-stage renal failure. After renal transplantation, no recurrence of the disease occurs in the graft, but other organ involvement becomes evident later in life. Diabetes mellitus has been associated with cystinosis, but the mechanisms of impaired glucose tolerance have not yet been characterized. Here, we studied glucose tolerance, glucose constant decay (k-values), insulin and C-peptide by intravenous glucose tolerance test (IVGTT) in eight patients with infantile cystinosis (three with impaired GFR (CRF) and five after kidney transplantation (KTX)). For comparison, 15 age-matched children with CRF and 15 age-matched KTX patients were analysed. Both early and second insulin secretion phases were diminished in patients with infantile cystinosis, whereas in CRF, k-values were no different from control patients. After renal transplantation, k-values were significantly lower in cystinotic patients with a markedly reduced early insulin secretion phase. There was a significant negative correlation between k-values and age in patients with cystinosis. Repetitive IVGTTs in these patients demonstrated progressive but rather slow loss of first phase insulin secretion and C-peptide production, suggesting a slowly reducing secretion potential of the beta cell due to cystine storage. Conclusion Unlike type I diabetes mellitus, glucose intolerance in patients with infantile cystinosis is characterized by a slow, progressive loss of insulin secretion and C-peptide production. For these patients, the data indicate a 50% risk of developing glucose intolerance by the age of 18 years. We recommend to perform intravenous glucose tolerance tests at 5-year intervals. Received: 1 September 1997 / Accepted: 30 November 1997     

One‐hour plasma glucose concentration during the OGTT: what does it tell about β‐cell function relative to insulin sensitivity in overweight/obese children?

Tfayli H, Jung Lee S, Bacha F, Arslanian S. One‐hour plasma glucose concentration during the OGTT: what does it tell about β‐cell function relative to insulin sensitivity in overweight/obese children? Background: In adults 1‐h plasma glucose concentration cut‐point of 155 mg/dL (8.6 mmol/L) during the oral glucose tolerance test (OGTT) is a strong predictor of future diabetes risk. Objective: We tested the hypothesis that a 1‐h glucose concentration ≥155 mg/dL is associated with lower β‐cell function in overweight/obese youth. Research design and methods: One hundred and thirteen diabetes free overweight/obese youth aged 10–20 yr, underwent evaluation of β‐cell function during a 2 h hyperglycemic clamp ～225 mg/dL (12.5 mmol/L), and insulin sensitivity during a 3 h hyperinsulinemic–euglycemic clamp, and a standard 2 h OGTT. Body composition and abdominal adiposity were determined by DEXA and CT scan. The disposition index (DI) was calculated as the product of first‐phase insulin secretion and insulin sensitivity. Subjects were divided into two categories of 1‐h plasma glucose concentration: <155 mg/dL (n = 69) and ≥155 mg/dL (n = 44). Results: Youth with 1‐h glucose ≥155 mg/dL had lower DI than those with 1‐h glucose <155 mg/dL (295.1 ± 27.4 vs. 498.6 ± 37.7 mg/kg/min, p < 0.001), independent of the glucose tolerance status. In multiple regression models, DI was the strongest contributor to 1‐h glucose concentration explaining ～21% of its variance. Conclusions: Overweight/obese youth with 1‐h glucose ≥155 mg/dL during the oral glucose tolerance test have a significantly lower β‐cell function relative to insulin sensitivity even within the normal glucose tolerance range. Such youth may be at higher risk of future diabetes.     

Characterization of alterations in carbohydrate metabolism in children with Prader-Willi syndrome

OBJECTIVE: To study carbohydrate metabolism and insulin sensitivity and secretion in children and adolescents with Prader-Willi syndrome (PWS) compared with multifactorial obesity (MO) controls. PATIENTS AND METHODS: Seventy-five patients with PWS and 395 controls with MO were studied by oral glucose tolerance test. Insulin resistance (IR) and beta-cell function were assessed by homeostasis model assessment (HOMA), insulin glucose index, fasting insulin and insulin sensitivity index. RESULTS: The incidence of diabetes mellitus was 0% in PWS and 1.5% in MO, while carbohydrate intolerance was 9.3% in the former group and 7.6% in the latter (NS); basal insulin level (12 +/- 8.2 vs 22.3 +/- 25 mU/ml) and HOMA-IR (2.47 +/- 1.6 vs 4.18 +/- 5.05) were lower in PWS (p = 0.004 and 0.04, respectively), whereas HOMA beta-cell index was lower in PWS than in MO (59 +/- 42 vs 102 +/- 119, p = 0.03). ISI Composite was higher in PWS compared to MO (6 +/- 5.7 vs 4.18 +/- 5.05, p = 0.04). CONCLUSION: Patients with PWS presented lower insulin resistance and a dissociation between beta-cell secretion and the degree of obesity.     

Research of factors for glucose intolerance in mucoviscidosis]

Glucose tolerance has been assessed in cystic fibrosis (CF) children using HbA1C and plasma glucose and insulin determinations during an oral glucose tolerance test (OGTT), along with the determination of HLA-DR and islet-cell (ICA) and anti-insulin (IAA) antibodies. Of 49 patients (25 males, 24 females), aged 2 to 21 years (mean = 10.9 years), 29 had normal glucose tolerance (WHO criteria) during OGTT, 14 had impaired glucose tolerance (IGT) and 6 had an isolated hyperglycemia at 120 min. Fasting plasma glucose and HbA1C were significantly higher in IGT than in normoglycemic patients. However, these two parameters showed poor individual predictive value of disturbance in glucose tolerance. Of 14 patients with abnormal OGTT, 7 were aged below 10 years, with 2 as young as 5 years; 8 patients were females. HLA antigens characteristic of type I diabetes tended to be found less frequently in CF patients than in the general population: 9% were DR3, 7% were DR4 and none was DR3/DR4. There were no HLA differences according to glucose tolerance. ICA and IAA were respectively detected in only one patient. Stimulated plasma insulin was low but did not correlate with glucose tolerance. In conclusion, impaired glucose tolerance is common in cystic fibrosis and can be found early in life. Although insulin secretion is decreased in this population, it does not seem to be the only factor responsible for impaired glucose intolerance. The absence of the genetical and immunological characteristics of type I diabetes confirms that glucose intolerance in cystic fibrosis is due to other pathogenetic mechanisms.     

Carbohydrate metabolism changes in cystic fibrosis

AIMS: To assess the prevalence of impaired glucose tolerance (ITG) and diabetes mellitus (DMRCF) in a group of patients with cystic fibrosis (CF). To study clinical status-related variables and to compare age with the evolution of their carbohydrate metabolism (CHM). PATIENTS AND METHODS: Thirty patients with CF (1.5-26 years). Oral glucose tolerance test (OGTT) in 28 patients. RESULTS: Three patients (10%) showed ITG and four DMRCF (13.3%). CF patients with impaired CHM (ICHM) were older (p = 0.006), and had longer times since diagnosis and first sputum colonization (p = 0.001, p < 0.001). Homozygous deltaF508 mutation was significant (p = 0.001). Insulin peak, area under the curve for insulin, insulin resistance, insulin sensitivity, and pancreatic beta-cell function were all significant. CONCLUSIONS: ICHM was present in 23.3%. Age, time since diagnosis of CF, first sputum colonization and homozygous deltaF508 mutation were significantly associated. CHM in patients with CF is similar to that in the population without CF in the early years.     

Early detection of impaired glucose tolerance in patients with cystic fibrosis and predisposition factors

INTRODUCTION: The number of patients with glucose tolerance alterations associated with cystic fibrosis (CF) has increased, probably due to the greater survival rate among sufferers of this disease. We studied impaired glucose tolerance (IGT) in patients with CF and investigated whether its appearance has any relationship with age, sex, genetic mutation and/or the degree of clinical involvement. We assessed the parameters that might allow early detection. PATIENTS AND METHODS: In 28 patients with CF (14 M, 14 F; aged 22 months to 18 years), sex, genetic mutation, nutritional status and the degree of pancreatic and pulmonary involvement were recorded. The metabolic study included glycosylated hemoglobin (HbA1c) determination, oral glucose tolerance test (OGTT) and intravenous glucose tolerance tests (IVGTT). RESULTS: In the patients with CF, 35.71% showed impaired glucose tolerance (IGT) and 3.57% had diabetes mellitus. The patients with IGT and CF were 3.2 years older than those with normal glucose tolerance (NGT; p<0.05), but no significant differences were found regarding sex, anthropometric measurements, percentage of pulmonary gammagraphic involvement, Shwachman-Kulczycki test or HbA1c. In the OGTT, the patients homozygous for the deltaF508 mutation had higher blood glucose values than the heterozygous group (p=0.03), but these values were not higher than those in patients with other mutations. During the OGTT, blood insulin values at 30' were reduced in patients with IGT compared to patients with NGT (p<0.02) and the insulin peak occurred at 100.9+/-24.3 min compared to 65.3+/-21.8, respectively (p<0.05). In the IVGTT, 82.14% of the patients had reduced insulin levels at 1 and 3 min (I1'+3'). No differences in the blood glucose levels during the OGTT were found between patients with normal I1'+3' values and patients with reduced values. CONCLUSIONS: A high percentage of patients with CF also present with IGT. This increases with age and is more common among patients homozygous for the deltaF508 mutation and is not related to clinical status. Alterations in the kinetics of insulin secretion play an important role in the appearance of IGT and CF. We suggest that the OGTT is a more sensitive method than IVGTT for identifying early alterations in CF-related diabetes mellitus.     

Continuous glucose monitoring system in the screening of early glucose derangements in children and adolescents with cystic fibrosis

BACKGROUND: In cystic fibrosis (CF), diabetes mellitus (DM) is associated with progression of pulmonary disease and nutritional impairment. AIM: To compare oral glucose tolerance test (OGTT) and continuous glucose monitoring system (CGMS) in patients with CF with early glucose derangements. PATIENTS AND METHODS: Thirty-two patients with CF (5-20 years) with intermediate glucose values > 7.7 mmol/l during OGTT received a CGMS registration. Patients were classified into those with normal glucose tolerance (NGT), impaired glucose tolerance (IGT) and DM, according to glucose values at 120 min of OGTT and during CGMS. Furthermore BMI z-scores, forced expiratory volume in 1 second (FEV1%), number of respiratory infections/year, enzyme supplementation, and HbA1c were evaluated. RESULTS: OGTT and CGMS derangements were in agreement in 43.7% of the patients. BMI z-scores, FEV1%, number of respiratory infections/ year, enzyme supplementation, and HbA1c did not differ among the three groups. HbA1c, correlated positively with 120 min OGTT (r = 0.34; p = 0.059), CGMS area (r = 0.35; p = 0.048) and the number of respiratory infections, and negatively with FEV1%. CONCLUSIONS: Intermediate glucose values during OGTT should be considered as a screening test in patients with CF. CGMS can be useful in studying the early occurrence of glucose derangements in selected patients.