Postprandial hyperinsulinaemic hypoglycaemia and type 1 diabetes mellitus.

A patient with severe postprandial hyperinsulinaemic hypoglycaemia (PPHH) for 4 years developed type 1 diabetes mellitus. She had no insulin or insulin receptor antibodies but was positive for islet cell and glutamic acid decarboxylase (GAD) antibodies. PPHH prior to the onset of type 1 diabetes mellitus has not been previously described and may be a prodrome of type 1 diabetes mellitus.     

Postprandial chylomicron clearance rate in late teenagers with diabetes mellitus type 1

A delayed chylomicron (CM) clearance rate, a known risk factor for atherosclerosis, has been described in adults with diabetes type 1 (DM1). We determined the CM clearance rate in late teenagers with DM1, and the relationship between CM clearance rate and elevated plasma lipid concentrations in DM1 teenagers in poor metabolic control (as characterized by HbA(1c) percentage). Plasma lipids and CM clearance were determined in nine patients with DM1 (mean age +/- SD: 17.5 +/- 0.6 y) and four healthy controls (mean age +/- SD: 20.1 +/- 0.8 y), by measuring breath (13)CO(2), plasma triglyceride, retinyl palmitate, and (13)C-labeled oleic acid concentrations, after oral administration of a fat-rich meal together with vitamin A and (13)C-oleic acid. In patients with DM1, fasting triglyceride and cholesterol concentrations were positively correlated with HbA(1c) percentage (p < 0.05). Neither in DM1 patients, nor in controls, was an elevated triglyceride concentration (above 1.7 mmol/L) found. Yet, in 22% of DM1 patients, cholesterol concentration was above 5.2 mmol/L, but not in any of the controls. CM clearance rate in DM1 patients was similar to that in controls and did not significantly correlate with HbA(1c) percentage. Fasting lipid concentrations in DM1 patients were not significantly correlated with CM clearance rate. Present data indicate that elevated lipid concentrations in late teenagers with DM1 are not attributable to a delay in CM clearance rate. A delayed CM clearance rate at late teenager age is not a risk factor contributing to the increased risk for atherosclerosis in DM1.     

Mosaic Turner syndrome and hyperinsulinaemic hypoglycaemia

BACKGROUND: A common and well recognised feature of Turner's syndrome (partial or total monosomy X) is impaired glucose tolerance or type 2 diabetes mellitus. A small percentage of patients with Turner's syndrome have a complex mosaic karyotype with atypical clinical features and mental retardation. METHODS/PATIENT: We report the first case of a child with a complex mosaic Turner genotype and hyperinsulinaemic hypoglycaemia responsive to diazoxide therapy. RESULTS: Cytogenetic analysis showed four cell lines: one with 45,X; the others with an additional small ring chromosome, a small marker chromosome, and both the ring and marker chromosomes, respectively. FISH studies showed the abnormal chromosomes to originate from an X. The X inactivation locus (XIST) was present in the ring, but not in the marker chromosome. CONCLUSIONS: The recognition of hypoglycaemia in children with atypical Turner's syndrome is important as persistent hypoglycaemia may lead to brain damage in addition to the risk of mental retardation. Further studies are required to understand whether the mosaic over--or underexpression of unidentified X chromosome gene(s) in the pancreatic beta-cells leads to hyperinsulinaemic hypoglycaemia.     

Persistent hyperinsulinaemic hypoglycaemia in infancy

Persistent hyperinsulinaemic hypoglycaemia in infancy (PHHI) is a heterogeneous condition characterised by unregulated insulin secretion in response to a low blood glucose level. It is the most common cause of severe and persistent hypoglycaemia in neonates. It is extremely important to recognise this condition early and institute appropriate management to prevent significant brain injury leading to complications like epilepsy, cerebral palsy and neurological impairment. Histologically, PHHI is divided mainly into three types—diffuse, focal and atypical disease. Fluorine-18-l-3,4-dihydroxyphenylalanine positron emission tomography (18F-DOPA-PET/CT) scan allows differentiation between diffuse and focal diseases. The diffuse form is inherited in an autosomal recessive (or dominant) manner whereas the focal form is sporadic in inheritance and is localised to a small region of the pancreas. The molecular basis of PHHI involves defects in key genes (ABCC8, KCNJ11, GCK, SLC16A1, HADH, UCP2, HNF4A and GLUD1) that regulate insulin secretion. Focal lesions are cured by lesionectomy whereas diffuse disease (unresponsive to medical therapy) will require a near-total pancreatectomy with a risk of developing diabetes mellitus and pancreatic exocrine insufficiency. Open surgery is the traditional approach to pancreatic resection. However, recent advances in laparoscopic surgery have led to laparoscopic near-total pancreatectomy for diffuse lesions and laparoscopic distal pancreatectomy for focal lesions distal to the head of the pancreas.     

Fear and other disturbances of severe hypoglycaemia in children and adolescents with type 1 diabetes mellitus

OBJECTIVE: To study perceived occurrence and magnitude of fear and other disturbances of severe hypoglycaemia in children and adolescents with type 1 diabetes mellitus (DM) receiving intensive treatment with active education and psychosocial support. PATIENTS AND METHODS: Out of a geographic population of 112 patients <19 years of age and their families, with a DM duration >1 year, HbA1c mean+/-SD 6.7+/-0.9 (method 1.15% below DCCT level), 74 responded to a questionnaire. Visual analogue scales, 5-graded Likert scales and open questions were used. RESULTS: Global quality of life was high, but lower among patients with severe hypoglycaemia within the last year (p = 0.0114). Worse perceived health was correlated to higher HbA1c year mean (r = 0.32, p = 0.0227). Patients and parents regard severe hypoglycaemia more as a problem (p <0.0001) and the risk of it more disturbing than mild hypoglycaemia (p <0.0001), insulin injections (p <0.0001) or blood glucose determinations (p <0.0001). The disturbance is higher during exercise, disco/party and in travel situations. Severe hypoglycaemia with unconsciousness causes more fear than severe hypoglycaemia needing assistance but without unconsciousness (p = 0.0001) or the potential late complications of DM (p = 0.0014). Severe hypoglycaemia needing assistance but without unconsciousness causes more fear than mild hypoglycaemia (p = 0.0001) and diabetic ketoacidosis (p <0.0001) but less than the potential late complications of DM (p = 0.0034). CONCLUSIONS: Severe hypoglycaemia frequently causes fear and various disturbances in spite of active education and psychosocial support. There is a potential for increased quality of life from interventions targeted at the prevention of severe hypoglycaemia. Further research and improved strategies for the prevention of severe hypoglycaemia are needed.     

Pubertal stage and hypoglycaemia counterregulation in type 1 diabetes

Aims: To compare physiological and autonomic responses to acute hypoglycaemia in diabetic children in pre-, mid-, and post-pubertal stages of development. Methods: Twenty seven children (8 pre-pubertal, 7 mid-pubertal, 12 post-pubertal) with type 1 diabetes were studied. Hypoglycaemia was induced by insulin infusion until an autonomic reaction (R) was identified. Counterregulatory hormone levels were measured at baseline, R, R+15, and R+30 minutes. Haemodynamic changes and sweat production were measured. Results: The mean blood glucose level at R was lower in pre-pubertal than mid-pubertal children (2.0 v 2.5 mmol/l), and was positively correlated with HbA_1c. Glucagon and noradrenaline responses to hypoglycaemia were minimal in all children. A brisk increase in pancreatic polypeptide (PP) concentration only occurred in post-pubertal children. Only two children showed a sweating response to hypoglycaemia. Conclusions: The blood glucose level at which sympatho-adrenal responses to hypoglycaemia were activated was associated with glycaemic control, and varied with pubertal stage. As in adults, the glucagon response to hypoglycaemia was deficient within a few years of developing diabetes. However, sweating and secretion of PP in response to hypoglycaemia did not occur until after puberty, indicating some qualitative differences from adults.     

Treatment of hyperinsulinaemic hypoglycaemia with nifedipine

We report on two children with mild persistent hyperinsulinaemic hypoglycaemia. In both, oral nifedipine treatment (0.7 and 2.0 mg/kg per day respectively) had a significant clinical effect. In one case, nifedipine monotherapy prevented hypoglycaemia; in the second case, the dosage and the side-effects of other substances could be reduced, thus circumventing surgical therapy. Conclusion Nifedipine treatment has a favourable effect on the clinical course of patients with mild hyperinsulinism. It represents a valuable new substance for the treatment of this disorder. Received: 3 March 1998 / Accepted: 3 August 1998     

Neuropathy and type 1 diabetes mellitus

Diabetic neuropathy is the most common type of neuropathies. It affects patients with both type 1 and type 2 diabetes, but it progresses more rapidly and its manifestations are more severe in type 1 diabetes. Although there has been a significant progress in the understanding of the clinical aspects of these conditions, many questions remain unanswered. Peripheral and autonomic neuropathy are strong risk markers for future mortality. Diabetic autonomic neuropathy is a serious and common complication of diabetes. DAN frequently coexists with other peripheral neuropathies and other diabetic complications, but DAN may be isolated, frequently preceding the detection of other complications. The presence of the autonomic diabetic neuropathy significantly influences the regulatory function of microcirculation, which may predispose to the occurrence of different late diabetic complications.     

Rate of hypoglycaemia and insulin dosage in children during the initial therapy of type 1 diabetes mellitus

Hypoglycaemia is a major side-effect of insulin treatment. It is known that young children with type 1 diabetes mellitus (T1DM) show a higher risk of hypoglycaemia than older children. This study was performed to analyse the incidence of hypoglycaemia within the first 14 days (day 1–day 14) of insulin treatment in children at the onset of T1DM and to evaluate the influence of age and insulin dosage. The Paediatric Quality Initiative (DPV), including data from 121 centres in Germany and Austria, provided anonymous data of 1,680 patients (age 0.7–18.8 years; 799 girls) at the onset of T1DM. Hypoglycaemia was defined as a blood glucose level (BG) <2.8 mmol/l (50 mg/dl). The hypoglycaemia rate rose continuously from day 2 (4.8%) to day 5 (11.2%) and then remained stable between 8.7%–11.2% until day 14. The hypoglycaemia rate was higher in younger than in older children ( P <0.0001). Multiple regression analysis revealed an influence of age ( P <0.0001), insulin dosage ( P =0.0034), and route of initial treatment ( P =0.0052) on the hypoglycaemia rate. From day 2 to day 14, the insulin dosage itself was higher in females than in males ( P =0.0147), in patients with high HbA1c ( P =0.0001), high BG ( P <0.0001), or low pH ( P <0.0001). There was no influence of age on the insulin dosage. Conclusion: During the first 14 days after onset of type 1 diabetes mellitus, young children, intravenous-treated patients and patients receiving a high insulin dosage are at particular risk of developing hypoglycaemia. In order to avoid hypoglycaemia, blood glucose should be measured frequently and the insulin dosage should be carefully adjusted. Low blood glucose levels should be treated promptly.     

Pubertal stage and hypoglycaemia counterregulation in type 1 diabetes.

AIMS: To compare physiological and autonomic responses to acute hypoglycaemia in diabetic children in pre-, mid-, and post-pubertal stages of development. METHODS: Twenty seven children (8 pre-pubertal, 7 mid-pubertal, 12 post-pubertal) with type 1 diabetes were studied. Hypoglycaemia was induced by insulin infusion until an autonomic reaction (R) was identified. Counterregulatory hormone levels were measured at baseline, R, R+15, and R+30 minutes. Haemodynamic changes and sweat production were measured. RESULTS: The mean blood glucose level at R was lower in pre-pubertal than mid-pubertal children (2.0 v 2.5 mmol/l), and was positively correlated with HbA1c. Glucagon and noradrenaline responses to hypoglycaemia were minimal in all children. A brisk increase in pancreatic polypeptide (PP) concentration only occurred in post-pubertal children. Only two children showed a sweating response to hypoglycaemia. CONCLUSIONS: The blood glucose level at which sympatho-adrenal responses to hypoglycaemia were activated was associated with glycaemic control, and varied with pubertal stage. As in adults, the glucagon response to hypoglycaemia was deficient within a few years of developing diabetes. However, sweating and secretion of PP in response to hypoglycaemia did not occur until after puberty, indicating some qualitative differences from adults.     

Plasma C peptide in hyperinsulinaemic hypoglycaemia.

We describe two children with hypoglycaemia due to pancreatic beta cell hyperactivity. Both had low serum insulin but raised plasma C peptide concentrations when hypoglycaemic. Measurement of C peptide is valuable in the diagnosis of hyperinsulinaemic hypoglycaemia in children.     

肠道微生物与1型糖尿病

研究显示肠道微生物在免疫相关性疾病的发病中起到重要的作用.1型糖尿病作为一种自身免疫性疾病,其发病机制与肠道微生物的关系的研究也逐渐增多.肠道微生物的改变是1型糖尿病发病的重要危险因素,这在动物模型研究中已经得到证实.该文就肠道微生物对1型糖尿病的作用进行综述,并探讨微生物对宿主免疫反应的影响以及1型糖尿病未来可能的预防及治疗方案.     

Genetics of type 1 diabetes mellitus

Type 1 Diabetes Mellitus is a complex and polygenic disease due to gene-environment interactions. The role of genetic background of diabetes has been extensively investigated. However, final conclusions have not yet been reached. Family and twin studies have shown that genetic factors are important contributors to the genetic risk of the disease. Although more than 18 diabetes-predisposing genes have been reported to date, only the major histocompatibility complex (HLA) region on chromosome 6p21 (IDDM1) and the insulin gene on chromosome 11p15 (IDDM 2) have been conclusively associated with susceptibility to type 1 diabetes. However, it has been shown recently that cytotoxic lymphocyte antigen 4 (CTLA4) on chromosome 2q33 (IDDM12) and LYP/PTPN22 on chromosome 1p13 also contribute to the genetic risk of T1DM. The article reviews the recent advances in this field. By identifying new loci or reanalyzing the known ones and with the help of more powerful studies, it is possible in the future to be able to shed more light on the complex field of the genetics of type 1 diabetes and to further understand the pathophysiology of the disease, which will allow us eventually to treat or prevent it.     

Biochemical studies in patients with hyperinsulinaemic hypoglycaemia

Hyperinsulinaemic hypoglycaemia (HH) is characterised by the dysregulated secretion of insulin from the pancreatic β-cell. It is a major cause of severe and persistent hypoglycaemia in the newborn period. There have been no previous studies assessing the various biochemical alterations at the time of hypoglycaemia in relation to the severity of the hypoglycaemia. Biochemical and clinical data were collected on 90 neonates (gestational age range, 32–42 weeks) with a diagnosis of HH [(based on glucose requirement?>?8 mg/kg/min) and the biochemical profile of insulin action (low beta-hydroxybutyrate and fatty acid concentrations)] who had undergone fasting studies. The results showed that (a) the serum insulin level measured at the time of hypoglycaemia had no correlation with the severity of hypoglycaemia, (b) the serum insulin level was undetectable despite severe hypoglycaemia in a significant proportion of patients, (c) there was no correlation between the birth weight and the insulin level at the time of hypoglycaemia, (d) the suppression of ketogenesis was more marked than that of the non-esterified fatty acids. This study suggests that the diagnosis of HH should not rely solely on a raised serum insulin level at the time of hypoglycaemia but on the constellation of clinical and biochemical findings.     

Teenage pregnancy in type 1 diabetes mellitus

Carmody D, Doyle A, Firth RGR, Byrne MM, Daly S, Mc Auliffe F, Foley M, Coulter‐Smith S, Kinsley BT. Teenage pregnancy in type 1 diabetes mellitus Younger maternal age at delivery has been linked to adverse reproductive outcomes. Pregnancy complicated by type 1 diabetes mellitus (T1DM) is also associated with adverse pregnancy outcomes. Optimising diabetic glycaemic control prior to pregnancy is known to reduce the rate of congenital abnormalities and improve pregnancy outcomes. Teenage pregnancies are not usually planned and little data exist on teenage pregnancy complicated by T1DM. We sought to identify the glycemic control achieved in teenage pregnancy with T1DM and to clarify if there is an associated increase in adverse pregnancy outcomes compared to those seen in older women with T1DM. We compared outcomes in 18 teenagers (TG) with 582 older women with T1DM (CON) from 1995–2007. TG booked to the combined diabetes‐obstetrical service at a median gestational age of 11 weeks (range 6–22) compared to 7 weeks in CON (range 4–40, p < 0.02). Glycaemic was worse in TG compared to CON at 13, 26 and 35 weeks gestation, despite higher insulin doses. First trimester miscarriage rate did not differ between groups. Major congenital anomaly rate was 6.2% (1/16) compared to 3.2% in CON. This preliminary study has demonstrated that pregnant teenage women with T1DM book later to specialised care and have worse glycaemic control in pregnancy compared to older women with T1DM. This group also appear to be more insulin resistant than older women in early pregnancy. Our data would suggest that teenagers with type 1 diabetes mellitus may constitute a high‐risk group for adverse pregnancy outcomes.     

Rhino-orbital-cerebral mucormycosis in type 1 diabetes mellitus

AIM : To describe the presentation and outcome of rhino-orbital-cerebral mucormycosis (ROCM) in adolescents with type 1 diabetes mellitus (T1 DM).Methods : the medical records of six patients of T1 DM with ROCM admitted between October 2001 to January 2004 were analysed.Results : the mean (± SD) age and duration of DM of these patients were 16.1 ±3.0 years and 26.3 ± 24.9 months respectively. Four patients had ROCM at presentation, while two developed it during their hospital stay when recovering from diabetic ketoacidosis. Proptosis (100%) and ptosis (100%) were the most common symptoms, and ophthalmoplegia (85%) and vision loss (85%) were the most common signs. Maxillary sinus (85%) was the commonest paranasal sinus to be involved. All patients received amphotericin B and had appropriate surgery except one. Four patients survived. Patients who had altered sensorium, facial necrosis, palatal perforation and cerebral involvement at presentation had poor outcome.Conclusion : High index of suspicion of ROCM in T1 DM and combined approach with amphotericin B and appropriate surgery is rewarding.