Insulin sensitivity and beta-cell secretion in thalassaemia major with secondary haemochromatosis: assessment by oral glucose tolerance test

Diabetes mellitus in patients with thalassaemia major is caused by secondary haemochromatosis due to transfusional iron overload. The pathogenetic mechanisms leading from siderosis to diabetes are still poorly understood. This study aimed at assessing the influence of insulin resistance and insulin deficiency on that process. Glucose, insulin and C-peptide levels during oral glucose tolerance tests (OGTT) from 36 thalassaemic patients with normal ( n=23), impaired ( n=6), or diabetic glucose tolerance ( n=7) and 32 control subjects were examined. Insulin secretion and insulin sensitivity were assessed by established calculated indices. Fasting, 2h and integrated glucose concentration were significantly increased in thalassaemic patients with normal glucose tolerance compared to controls (5.01/4.59 mmol/l, 6.33/5.17 mmol/l, and 844.2/739.3 mmol/l per min, respectively; all P<0.03). Patients with impaired glucose tolerance presented hyperinsulinaemia and delayed peak insulin during OGTT. The C-peptide/insulin ratio was decreased in patients with abnormal glucose tolerance compared to controls (5.85/7.33 x 10(3)pmol/l per min, P<0.03). It was negatively correlated with age in patients ( r=-0.45, P<0.01), but positively in controls ( r=0.43, P<0.03). Insulin sensitivity was significantly reduced in patients with impaired glucose tolerance or diabetes compared to controls. In addition, a significant decrease in patients with normal glucose tolerance was shown by two insulin sensitivity indices (all P<0.05). In thalassaemia patients, insulin sensitivity was negatively correlated with age. Insulin secretion capacity according to the homeostasis assessment model was significantly reduced in patient groups compared to controls (Kruskal-Wallis-test, P<0.004). CONCLUSION: Insulin resistance is of central importance for the development of diabetes mellitus in patients with secondary haemochromatosis. An additional early defect in beta-cell secretion cannot be excluded.     

Impaired glucose homeostasis in young adult thalassemic patients: a pilot study with acarbose

This study investigated the effects of the alpha-glucosidase inhibitor, acarbose, on glycemic control and insulin secretion in thalassemic patients with impaired glucose tolerance. The safety and tolerability of the drug were also evaluated. Nine patients (4 men and 5 women, aged 20-34 years) with beta-thalassemia major received a standardized nutritional test load prior to and following 3 months treatment with acarbose 100 mg t.i.d. Blood glucose, insulin and C-peptide levels were measured at 0, 60, 90 and 120 min post-loading. Plasma glucose levels after 3 months of acarbose treatment tended to be slightly lower than pre-treatment levels. Although fasting serum insulin and plasma C-peptide levels were unchanged after acarbose therapy, postprandial serum levels of both hormones were markedly reduced (by 24-47% and 19-32%, respectively, at 60-120 min post-loading). Body mass index, liver enzymes and serum lipids were unaltered following acarbose treatment. Gastrointestinal disturbances were mild and tended to decrease during the course of acarbose therapy. Acarbose is a well-tolerated agent for the management of thalassemic patients with glucose intolerance and normal or increased insulin secretion. It is possible that acarbose may prevent or delay progression from impaired glucose homeostasis to frank insulin-dependent diabetes mellitus.     

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.     

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.     

Glucose Metabolism and Insulin Secretion in Infants with Symptomatic Ventricular Septal Defect

ABSTRACT. Nineteen infants with symptomatic ventricular septal defect (VSD) were examined on, altogether, 26 occasions, when each was given an intravenous glucose tolerance test (IVGTT); concentrations of insulin- and C-peptide in plasma were determined. Comparisons were made with 14 healthy infants of the same age. The VSD infants were growth retarded with lower weight/age and length/age ratios. Glucose tolerance as indicated by glucose fasting levels and response to intravenous glucose tolerance test, including glucose disappearance rate, did not differ between the two groups. In response to the glucose load, insulin in plasma was significantly less in VSD infants. In response to the IVGTT, insulin secretion rate calculated from C-peptide levels in plasma was significantly elevated in the VSD group. We conclude that compared to healthy infants, those with symptomatic VSD have normal glucose tolerance, increased secretion rate of insulin, but decreased levels of circulating insulin in response to an intravenous glucose load. We suggest this is so because binding of insulin to peripheral receptors and/or insulin extraction in the liver somehow increases.     

Glucose metabolism and insulin secretion in infants with symptomatic ventricular septal defect

Nineteen infants with symptomatic ventricular septal defect (VSD) were examined on, altogether, 26 occasions, when each was given an intravenous glucose tolerance test (IVGTT); concentrations of insulin- and C-peptide in plasma were determined. Comparisons were made with 14 healthy infants of the same age. The VSD infants were growth retarded with lower weight/age and length/age ratios. Glucose tolerance as indicated by glucose fasting levels and response to intravenous glucose tolerance test, including glucose disappearance rate, did not differ between the two groups. In response to the glucose load, insulin in plasma was significantly less in VSD infants. In response to the IVGTT, insulin secretion rate calculated from C-peptide levels in plasma was significantly elevated in the VSD group. We conclude that compared to healthy infants, those with symptomatic VSD have normal glucose tolerance, increased secretion rate of insulin, but decreased levels of circulating insulin in response to an intravenous glucose load. We suggest this is so because binding of insulin to peripheral receptors and/or insulin extraction in the liver somehow increases.     

Insulin resistance is associated with decreased clinical status in cystic fibrosis

Patients with cystic fibrosis (CF) frequently have impaired glucose tolerance and progression to diabetes (DM) with clinical features of both insulin-dependent and non-insulin-dependent diabetes. One feature of non-insulin-dependent DM is decreased insulin sensitivity, also known as insulin resistance. The goal of this study was to determine whether patients with CF exhibit insulin resistance and to determine the potential effect of insulin resistance on clinical status. We also sought to determine whether insulin resistance is associated with a specific CF genotype. We studied 18 patients with CF (8 with normal glucose tolerance, 5 with impaired glucose tolerance, 5 with DM), and 20 lean control subjects matched for age, weight, and sex. All control subjects had normal glucose tolerance. The clinical status for each CF patient was determined according to a modified National Institutes of Health scoring system. Each subject underwent a three-step hyperinsulinemic euglycemic clamp (insulin doses of 10, 40, 120 mU/m ² per minute). Results from the 120 mU/m ² per minute infusion defined maximal glucose disposal rate (defined in milligrams per kilogram body weight per minute) at steady state with peripheral insulin levels 195 ± 20 mU/ml. Subjects with CF demonstrated insulin resistance (control subjects = 13.6 ± 1.1, patients with CF = 10.2 ± 1.6 mg/kg per minute; p = 0.003). When each subgroup was compared separately with control subjects, all subgroups were statistically insulin resistant (glucose disposal rate, patients with CF and normal glucose tolerance = 10.8; those with impaired glucose tolerance = 8.4; those with DM = 10.1 mg/kg per minute), and the patients with CF with impaired glucose tolerance were the most insulin resistant. When plotted versus glucose disposal rate, a striking positive correlation between worsened clinical status and insulin resistance ( r = 0.85) is demonstrated. Furthermore, there is no correlation between insulin resistance and fasting blood glucose, subject age, or percent ideal body weight (all r values not significant). In conclusion, patients with CF exhibit insulin resistance that is associated with worsened clinical status. We believe it is the combination of insulin resistance and decreased insulin secretion that is responsible for the high incidence of CF-related diabetes. (J Pediatr 1997;130:948-56)     

Verbesserung der Glukosetoleranz von Patienten mit Zystischer Fibrose unter pseudomonaswirksamer Chemotherpie

Background. For many patients with cystic fibrosis impaired glucose tolerance or even diabetes mellitus is becoming relevant with growing age. The influence of an anti-Pseudomonas chemotherapy on glucose homeostasis of cystic fibrosis patients was investigated. Patients and methods. In fourteen cystic fibrosis patients aged between 7 and 35 years glucose tolerance was tested by standard oral glucose tolerance test in the beginning and at the end of a routine anti-Pseudomonas chemotherapy of fourteen days. Beside the blood glucose serum insulin was determinated. Results. According to the criteria of the American Diabetes Association three of the fourteen patients had an impaired glucose tolerance and another three had diabetes mellitus when tested at the beginning of anti-Pseudomonas chemotherapy. In four of these six patients glucose tolerance was normal at the end of the chemotherapy. Of the remaining two patients one fulfilled the criteria for impaired glucose tolerance and one for diabetes mellitus. In these patients insulin secretion was lower in the second test. Peak insulin was reached earlier while there was no significant improvement of early insulin response. Conclusion. The treatment of chronic airway infection in cystic fibrosis patients with impaired glucose tolerance or diabetes mellitus results in an improvement of glucose homeostasis by a better insulin sensitivity and less by improvement of early insulin response. In developing diagnostic protocols for screening of cystic fibrosis-related diabetes mellitus the impact of the concomitant therapy on glucose homeostasis should be considered.     

Prevalence of type 2 diabetes mellitus and impaired glucose tolerance in obese Argentinean children and adolescents

The aim of this study was to evaluate the prevalence of type 2 diabetes mellitus (DM2) and impaired glucose tolerance (IGT) in obese children and adolescents and to examine insulin resistance and insulin secretion. We studied 427 asymptomatic obese patients. DM2 and IGT were diagnosed by an oral glucose tolerance test. Insulin resistance and P-cell function were assessed by using homeostasis model assessment (HOMA), insulin/glucose index (I/GI), fasting insulin and insulin sensitivity index (ISI-composite). Thirty patients showed IGT (7%) and seven had DM2 (1.6%). The mean age was 10.7 +/- 3.5 years, the diabetic group being significantly older than the normal group (p < 0.01). The mean body mass index was 30 +/- 5.3 kg/m2 without significant differences between groups. beta-Cell function declined significantly in the patients with IGT and DM2, and insulin resistance increased significantly. Given the rather high prevalence of glucose metabolism impairment, children with obesity should undergo glucose tolerance testing for appropriate therapeutic intervention.     

Oral glucose tolerance test in children and adolescents: positives and pitfalls

Objectives:   To describe the glycaemic status (assessed by an oral glucose tolerance test (OGTT)) and associated comorbidities in a cohort of Australian children and adolescents at risk of insulin resistance and impaired glucose homeostasis (IGH).
Methods:   Twenty-one children and adolescents (three male, 18 female) (18 Caucasian, one Indigenous, two Asian) (20 obese, one lipodystrophy) referred to the Paediatric Endocrinology and Diabetes Clinic underwent a 2-h OGTT with plasma glucose and insulin measured at baseline, + 60 and + 120 min. If abnormal, the OGTT was repeated.
Results:   The mean (SD) age was 14.2 (1.6) years, BMI 38.8 (7.0) kg/m² and BMI-SDS 3.6 (0.6). Fourteen patients had fasting insulin levels >21 mU/L. Type 2 diabetes mellitus was diagnosed in one patient, impaired glucose tolerance (IGT) in four patients and impaired fasting glycaemia (IFG) in one patient. Despite no weight loss, only one patient had a persistently abnormal OGTT on repeat testing. Three patients with IGH were medicated with risperidone at the time of the initial OGTT. One patient who had persistent IGT had continued risperidone. The other two patients had initial OGTT results of IGT and diabetes mellitus type 2. They both ceased risperidone between tests and repeat OGTT showed normal glycaemic status.
Conclusions:   Use of fasting glucose alone may miss cases of IGH. Diagnosis of IGT should not be made on one test alone. Interpretation of glucose and insulin responses in young people is limited by lack of normative data. Larger studies are needed to generate Australian screening recommendations. Further assessment of the potential adverse effects of atypical antipsychotic medication on glucose homeostasis in this at-risk group is important.     

糖耐量减低肥胖儿童胰岛素原和真胰岛素水平测定意义

目的　探讨血清胰岛素原 (PI)及真胰岛素 (TI)测定对肥胖并糖耐量异常患儿的临床意义。方法　选择肥胖并糖耐量减低 (IGT)患儿 2 1例 ,肥胖糖耐量正常 (NGT) 5 2例 ,正常对照组 4 0例。测定各组空腹血清PI、TI、血糖 (G)、胰岛素 (I)和C 肽 (C P) ,并计算PI/I、PI/C P、PI/TI及胰岛素抵抗指数。结果　 1.肥胖并IGT和并NGT两组患儿比较 ,G、PI、C P及胰岛素抵抗指数均明显增加 (P均 <0 .0 1)。 2 .IGT组糖尿病阳性家族史明显高于NGT组 (P =0 .0 2 4 )。结论　高PI、高C P和胰岛素抵抗是肥胖并IGT患儿的突出表现 ,可能是儿童2型糖尿病的预示指标。有糖尿病阳性家族史肥胖儿童更应警惕IGT发生     

Glucose tolerance status in 510 children and adolescents attending an obesity clinic in Central Italy

Brufani C, Ciampalini P, Grossi A, Fiori R, Fintini D, Tozzi A, Cappa M, Barbetti F. Glucose tolerance status in 510 children and adolescents attending an obesity clinic in Central Italy. Childhood obesity is epidemic in developed countries and is accompanied by an increase in the prevalence of type 2 diabetes (T2DM). Aims: Establish prevalence of glucose metabolism alterations in a large sample of overweight/obese children and adolescents from Central Italy. Methods: The study group included 510 overweight/obese subjects (3–18 yr). Oral glucose tolerance test (OGTT) was performed with glucose and insulin determination. Homeostatic model assessment of insulin resistance (HOMA‐IR) and insulin sensitivity index (ISI) were derived from fasting and OGTT measurements. Beta‐cell function was estimated by insulinogenic index. Fat mass was measured by dual‐energy x‐ray absorptiometry. Results: Glucose metabolism alterations were detected in 12.4% of patients. Impaired glucose tolerance (IGT) was the most frequent alteration (11.2%), with a higher prevalence in adolescents than in children (14.8 vs. 4.1%, p < 0.001); silent T2DM was identified in two adolescents (0.4%). HOMA‐IR and glucose‐stimulated insulin levels were higher in patients with IGT than individuals with normal glucose tolerance (HOMA‐IR = 4.4 ± 2.5 vs. 3.4 ± 2.3, p = 0.001). Fat mass percentage and insulinogenic index were not different between the two groups. In multivariate analysis, age, fasting glucose, and insulin resistance influenced independently plasma glucose at 120 min of OGTT. Individuals with combined impaired fasting glucose/IGT (IFG/IGT) and T2DM were older and had reduced plasma insulin values at OGTT when compared to patients with simple IGT. Conclusions: Glucose metabolism alterations are frequently found among children and adolescents with overweight/obesity from Central Italy. Age, fasting glucose, and insulin resistance are main predictors of IGT. We suggest the use of OGTT as a screening tool in obese European adolescents.     

Abnormal glucose tolerance in Egyptian beta-thalassemic patients: possible association with genotyping

BACKGROUND: Type 1 diabetes mellitus (DM) is a frequent complication in patients with beta-thalassemia. It is believed to be due to the damage inflicted by iron overload of the pancreatic beta cells. Liver disorders and genetic influences seem to be additional predisposing factors. OBJECTIVE: To study the prevalence of diabetes and impaired glucose tolerance (IGT) in transfusion-dependent Egyptian beta-thalassemic patients and to evaluate the possible role of genotyping in the pathogenesis of diabetes associated with beta-thalassemia. RESEARCH DESIGN and METHODS: A total of 56 transfusion-dependent beta-thalassemic patients aged 10-31 (mean age=15.9 +/- 5.7 yr), 32 males and 24 females, including 48 thalassemia major and eight thalassemia intermedia; compared to 15 age- and sex-matched controls. All were subjected to history and examination, laboratory investigations: complete blood count (CBC), serum ferritin, liver function tests, hepatitis B and C markers, fasting blood glucose, oral glucose tolerance test (OGTT) and fasting C-peptide. Genotyping for 16 mutations was assessed in thalassemic patients with abnormal glucose tolerance. RESULTS: The prevalence of diabetes was 10.4% (5 of 48) and IGT was 14.6% (7 of 48) among thalassemia major, whereas, none of thalassemia intermedia had abnormal glucose tolerance. Fasting C-peptide was lower in beta-thalassemic patients compared to controls (p <0.001); the level was significantly higher in patients complicated by diabetes or IGT compared with other thalassemic patients (p <0.001). Chronic hepatitis C was detected in all patients (100%) with abnormal glucose tolerance. Genotyping showed that IVS II nt 745 was detected in 77.7% of cases with abnormal glucose tolerance. CONCLUSIONS: Abnormal glucose tolerance is common in multiply transfused beta-thalassemia major patients, which could be attributed to progressive and early loss of beta-cell mass, along with persistent insulin resistance. Chronic hepatitis C may play a role in the development of abnormal glucose tolerance. An association between diabetes and genotyping IVS II nt 745 was found. Patients with this particular genotype are advised to check their blood glucose every 6 months to detect early occurrence of diabetes.     

Glucose metabolism and insulin secretion in children with cyanotic congenital heart disease

The aim of the study was to reveal differences in carbohydrate metabolism in children with cyanotic congenital heart diseases (CHD). Thirteen children with diseases of these kinds were investigated with regard to glucose tolerance and insulin secretion and comparisons were made with healthy controls of the same age. Investigations included an intravenous glucose tolerance test, insulin response to the glucose load in plasma and insulin secretion rate. The results reveal lower fasting glucose levels and signs of a higher insulin secretion rate in the relatively few patients in the CHD group where C-peptide measurements were performed, but no differences in glucose tolerance. The reasons for the differences are unclear, but the chronic increases in circulating catecholamines in combination with the impaired nutritional status of these children with CHD are probably the most important factors. We conclude that these divergences in carbohydrate metabolism should be emphasized in the care of children with CHD.     

Postprandial hyperlipidemia after a fat loading test in minority adolescents with type 2 diabetes mellitus and obesity

The continuing increase in the incidence of type 2 diabetes mellitus (DM2) and obesity in children and adolescents is attributable to excessive caloric intake. Abnormal lipid metabolism in the postprandial state leads to long exposure of the vasculature to hyperlipidemia. Most children and adolescents with DM2 are obese, and many have fasting hypertriglyceridemia. Clustering of hyperlipidemia, DM2 and obesity increases the risk for cardiovascular disease. We therefore studied lipids, insulin, C-peptide, and glucose in response to an oral fat load simulating the fat content of a high-fat, fast-food meal in 12 type 2 diabetic obese, 15 non-diabetic obese, and 12 non-diabetic non-obese (control) adolescents (aged 10-19 yr; 87% African-Americans). All three groups were age-, sex-, and sexual maturation-matched. Mean body mass indices were similar in the diabetes and obese groups (32.7 +/- 1.1 vs 35.8 +/- 1.6 kg/m2). All patients with DM2 had fasting C-peptide > 0.2 nmol/l (0.7 ng/ml) and negative diabetes-associated autoantibodies. Serum total cholesterol, triglyceride, high- and low-density lipoprotein cholesterol, insulin, C-peptide, and plasma glucose levels were measured at 0, 2, 4, and 6 h after the fat load. The area under the curve (AUC) was calculated by trapezoidal estimation. Triglyceride AUC was significantly greater in the diabetes group than in the other two groups (15.7 +/- 2.9 vs 9.2 +/- 0.7 and 7.5 +/- 0.7 mmol x h/l [1389 +/- 258 vs 819 +/- 60 and 663 +/- 62 mg x h/dl]; p < 0.02 and <0.004, respectively), as were insulin, C-peptide, and glucose AUCs. Incremental triglyceride response (delta triglyceride = peak - fasting) in the diabetes group was significantly higher than that in the control group (2.1 +/- 0.7 vs 0.8 +/- 0.1 mmol/l 189.7 +/- 58.4 vs 71.2 +/- 11.1 mg/dl]; p < 0.04). Insulin resistance was estimated using the homeostasis model assessment (HOMA), which was greater in the diabetes group than in the obese and control groups (14.4 +/- 2.8 vs 5.2 +/- 0.8 and 3.2 +/- 0.4; p < 0.001 and < 0.0001, respectively). The diabetes group was divided into subgroups of high and normal fasting triglycerides on the basis of triglyceride levels above and below the 95th percentile. The delta triglyceride in the subgroup with high fasting triglycerides was substantially greater than in the subgroup with normal fasting triglycerides (3.4 +/- 1.1 vs 0.8 +/- 0.2 mmol/l [305.2 +/- 96.8 vs 74.2 +/- 18.0 mg/dl]; p < 0.001). Total cholesterol and triglyceride AUCs were much greater in the high vs normal fasting triglycerides subgroup (33.0 +/- 2.9 vs 24.2 +/- 1.9 and 23.6 +/- 3.5 vs 7.8 +/- 0.6 mmol x h/l [1274 +/- 113 vs 934 +/- 72 and 2085 +/- 309 vs 692 +/- 49 mg x h/dl]; p < 0.02 and <0.0001, respectively), as were insulin and C-peptide AUCs. HOMA was greater in the high vs normal fasting triglycerides subgroup (20.8 +/- 4.0 vs 8.0 +/- 1.6; p < 0.0001). In addition to elevated plasma glucose levels, there were no significant differences in either insulin or lipid parameters among the diabetes subgroup with normal fasting triglycerides, the obese group, and controls. Our data suggest that postprandial hyperlipidemia in response to a fat loading test is present in adolescents with DM2 who already have fasting hypertriglyceridemia. The degree of insulin resistance as an underlying abnormality--not DM per se--determines the degree of postprandial lipemia.     

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.     

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.     

Glucose Tolerance and Insulin Receptor Binding to Monocytes and Erythrocytes in Patients with Cystic Fibrosis

ABSTRACT. Cystic fibrosis (CF) is the most frequent life threatening hereditary disease in the Western World with an incidence of approximately 1:2000. Due to increasing survival rates the high frequency of abnormal glucose tolerance has become an important problem. We compared insulin concentrations during oral glucose tolerance test and insulin receptor binding to both monocytes and erythrocytes from 9 patients with CF, with results from 10 healthy controls of similar body weight. The insulin: glucose ratio was increased in the fasting state ( p < 0.05) in patients with CF compared to controls, indicating an increased insulin resistance in CF-patients. The total insulin secretion during oral glucose tolerance test as judged by the area beneath the insulin curve was similar in the two groups, but insulin secretion was significantly delayed in patients with CF. Insulin receptor binding to monocytes and the number of receptors were significantly increased ( p < 0.01 and 0.02, respectively) in patients with CF whereas the dissociation constant was similar in patients with CF and controls. No difference was observed in insulin receptor binding to erythrocytes between the two groups. No correlations were found between insulin receptor binding to monocytes or erythrocytes and glucose tolerance or insulin concentrations.     

Glucose tolerance and insulin receptor binding to monocytes and erythrocytes in patients with cystic fibrosis

Cystic fibrosis (CF) is the most frequent life threatening hereditary disease in the Western World with an incidence of approximately 1:2000. Due to increasing survival rates the high frequency of abnormal glucose tolerance has become an important problem. We compared insulin concentrations during oral glucose tolerance test and insulin receptor binding to both monocytes and erythrocytes from 9 patients with CF, with results from 10 healthy controls of similar body weight. The insulin: glucose ratio was increased in the fasting state (p less than 0.05) in patients with CF compared to controls, indicating an increased insulin resistance in CF-patients. The total insulin secretion during oral glucose tolerance test as judged by the area beneath the insulin curve was similar in the two groups, but insulin secretion was significantly delayed in patients with CF. Insulin receptor binding to monocytes and the number of receptors were significantly increased (p less than 0.01 and 0.02, respectively) in patients with CF whereas the dissociation constant was similar in patients with CF and controls. No difference was observed in insulin receptor binding to erythrocytes between the two groups. No correlations were found between insulin receptor binding to monocytes or erythrocytes and glucose tolerance or insulin concentrations.     

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.