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Background: This study aimed to describe the clinical outcomes of total pancreatectomy with islet autotransplantation (TP‐IAT) in Australia. Methods: Individuals selected for TP‐IAT surgery according to the Minnesota Criteria (Appendix) without evidence of diabetes were evaluated including time to transplantation from pancreatectomy, islet numbers infused and post‐transplantation HbA1c, C‐peptide, total daily insulin and analgesic requirement. Results: Sixteen individuals underwent TP‐IAT from Australia and New Zealand between 2010 and 2020. Two recipients are deceased. The median islet equivalents/kg infused was 4244 (interquartile range (IQR) 2290–7300). The median C‐peptide 1 month post‐TP‐IAT was 384 (IQR 210–579) pmol/L and at median 29.5 (IQR 14.5–46.5) months from transplant was 395 (IQR 139–862) pmol/L. Insulin independence was achieved in eight of 15 (53.3%) surviving recipients. A higher islet equivalents transplanted was most strongly associated with the likelihood of insulin independence (P < 0.05). Of the 15 surviving recipients, 14 demonstrated substantial reduction in analgesic requirement. Conclusion: The TP‐IAT programme in Australia has been a successful new therapy for the management of individuals with chronic pancreatitis including hereditary forms refractory to medical treatment to improve pain management with 50% insulin independence rates. This study describes the Australian experience of total pancreatectomy with islet autotransplantation. Sixteen individuals underwent total pancreatectomy with islet autotransplantation in Australia from 2010 to 2020. [ABSTRACT FROM AUTHOR]

Aims: To measure pancreatic area and exocrine function in young children with recent‐onset Type 1 diabetes to determine whether the exocrine pancreas is also affected in the pathophysiology of early childhood diabetes. Methods: Thirty‐two children (14 boys) aged 5.5 (4.5, 7.3) median (IQR) years presenting with recent‐onset Type 1 diabetes and 90 controls (44 boys) of similar age had ultrasound imaging of the pancreas. Children with Type 1 diabetes were receiving insulin and were without ketosis. Transverse and longitudinal areas of the pancreas were measured by digitalized outline. Pancreatic faecal elastase‐1 was analysed using an enzyme‐linked immunosorbent assay kit in recent‐onset Type 1 diabetes and 38 first‐degree relative control children. Results: Pancreatic area and exocrine function were reduced in Type 1 diabetes. Mean transverse area (SD) in Type 1 diabetes was 6.82 cm2 (1.61) vs. 8.31 cm2 (1.74) in controls, adjusted estimate (95% CI) 1.45 (‐2.12, ‐0.79), P < 0.001; longitudinal area was 1.28 cm2 (0.44) vs. 1.55 cm2 (0.43), adjusted estimate (95% CI) ‐0.27 (‐0.45, ‐0.09), P = 0.003. Faecal elastase‐1 levels in Type 1 diabetes were 455 (323, 833) ug/g, median (IQR) vs. 1408 μg/g (1031, 1989) in controls, P < 0.001. Conclusion: Pancreatic area and accompanying subclinical exocrine function were reduced in very young children with recent‐onset Type 1 diabetes. This supports changes in the exocrine pancreas in the pathophysiology of Type 1 diabetes presenting in early life. What's new?: Pancreatic volume and pancreatic exocrine function are reduced in adults and adolescents with Type 1 diabetes.Pancreatic volume is intermediate in adult first‐degree relatives, both with and without islet autoimmunity.Young children with recent‐onset Type 1 diabetes also have reduced pancreatic size and accompanying subclinical exocrine dysfunction.The exocrine pancreas is affected in the pathophysiology of Type 1 diabetes presenting in early life. [ABSTRACT FROM AUTHOR]

High risk HLA class II alleles account for 40% of the genetic susceptibility to type 1 diabetes in Caucasians, but the majority of the genetically predisposed do not develop the disease. This supports some environmental modification of the autoimmune destruction of beta cells that precedes type 1 diabetes. Identical twin studies and geographical variation in incidence also argue for a critical role of environmental factors. Attention has been directed to the possible harmful effect of cow's milk protein (or protective effect of breast-feeding) and enteric infections in early life. Natural history studies that follow children at increased risk of type 1 diabetes provide the best opportunity to study environmental triggers. The Australian Baby Diab Study has followed approximately 500 babies from birth who have a first-degree relative with type 1 diabetes. No prospective association between duration of breast-feeding or introduction of cow's milk and the development of islet autoimmunity was found. The same Australian cohort demonstrated a relationship between rotavirus infection and the first appearance or increase in islet antibodies. Enteroviral infection is seen more frequently in prediabetic children and prior to the onset of islet autoimmunity in Finnish cohorts. Environmental factors may interact. Breast milk protects against enteric infections; enteric infections in turn could increase immunity to dietary antigens by increasing intestinal permeability. It is also possible that an alteration in gut mucosal immune function in genetically susceptible individuals underlies any effect of dietary or viral proteins on the development of islet autoimmunity in early life. [ABSTRACT FROM AUTHOR]

We aimed to determine the natural history of borderline increases in albuminuria in adolescents with insulin-dependent (Type 1) diabetes mellitus (IDDM) and factors which are associated with progression to persistent microalbuminura. Fifty-five normotensive adolescents with IDDM and intermittent microalbuminura (overnight albumin excretion ratte of 20-200 micrograms min-1 on one of three consecutive timed collections, n = 29) or borderline albuminura (mean overnight albumin excretion rate of 7.2-20 micrograms min-1 on one of three consecutive timed collections, n = 30) were followed prospectively at 3 monthly intervals. The endpoint was persistent microalbuminuria defined as a minimum of three of four consecutive overnight albumin excretion rates of greater than 20 micrograms min-1. One hundred and forty-two adolescents with IDDM and normoalbuminura were also followed prospectively. Fifteen of the 59 patients (25.4%) with intermittent (9/29) or borderline (6/30) albuminura progressed to persistent microalbuminura (progressors) over 28 (15-50) months [median (range)] in comparison with two of the 142 patients with normoalbuminuria at entry (relative risk = 12.6; p = 0.001). Progressors to persistent microalbuminura were pubertal and had higher systolic (p = 0.02) and diastolic (p = 0.02) blood pressure, and HbA1c (p = 0.004) than non-progressors. All patients remained normotensive. Glomerular filtration rate, apolipoproteins, dietary phosphorus, protein and sodium intakes, and prevalence of smoking did not differ between progressors and non-progressors. Total renin was higher in the diabetic patients without a difference between progressors and non-progressors. In conclusion there is a relatively high rate of progression to persistent microalbuminuria in pubertal adolescents with borderline increases in albuminura and duration greater than 3 years. These patients require attention to minimize associated factors of poor metabolic control and higher blood pressure in the development of incipient nephropathy.

We aimed to examine the longitudinal relationship between lipoprotein(a) and haemoglobin A1c, albumin excretion rate, and puberty in peripubertal children with insulin-dependent diabetes. A total of 114 patients aged 11.5 +/- 3.6 years (mean (SD)) were followed prospectively for 15.2 +/- 2.8 months. Lipoprotein(a), apolipoproteinB-100, haemoglobin A1c, mean overnight albumin excretion rate and Tanner stage were determined at the beginning and end of the study period. Lipoprotein(a) and apolipoproteinB-100 were measured using nephelometry. This method was correlated with radioimmunoassay and there was no significant change in mean bias during the study. Lipoprotein(a) fell significantly over time (214, (152, 276); 160 (84, 236) mg l-1 geometric mean (0.95 confidence intervals), p < 0.001); apolipoproteinB-100 did not change. Lipoprotein(a) and apolipoproteinB-100 did not differ in 233 cross-sectional controls of similar age. The change in lipoprotein(a) did not correlate with a small fall in haemoglobin A1c or with overnight albumin excretion rate, Tanner stage or insulin dose. Separate analysis of male and female patients and prepubertal and pubertal patients continued to show a significant fall in lipoprotein(a) independent of change in haemoglobin A1c or albumin excretion rate. Likewise, 53 patients with a change in haemoglobin A1c of greater than 1%, and 20 patients who progressed from normal albumin excretion rate to albumin excretion rate above the 95th centile, showed no relationship between lipoprotein(a) and haemoglobin A1c or albumin excretion rate. In conclusion, longitudinal changes in lipoprotein(a) do not relate to metabolic control or early changes in albuminuria in young patients with insulin-dependent diabetes.

Recent evidence suggests the rise in urinary albumin excretion preceding diabetic nephropathy may represent a continuum. We therefore studied factors relating to albumin excretion rate in children with insulin-dependent diabetes. Normal overnight albumin excretion rate was determined in 690 healthy schoolchildren. The 95th centile was 7.2 micrograms min-1. Patients included 169 children with IDDM aged 12.4 +/- 3.1 years who performed 4.8 +/- 0.4 overnight collections during 15 +/- 0.5 months and were analysed cross sectionally. They were stratified accordingly to mean albumin excretion rate: normal < 7.2 micrograms min-1, borderline 7.2-20 micrograms min-1, microalbuminuria 20-200 micrograms min-1; 96/169 patients performed 6.4 +/- 0.2 overnight collections during 24 months follow-up and were analysed longitudinally. Cigarette smoking was determined by history and urine cotinine levels. Smoking correlated with albumin excretion rate, independent of age and other variables, in cross-sectional and longitudinal analysis (p < 0.003). Smoking was more prevalent in the borderline albuminuria and microalbuminuria groups (p < 0.004, p < 0.001). Mean HbA1c during follow-up and mean HbA1c since diagnosis were significantly higher in the microalbuminuric group, compared with the normal patient group. HbA1c since diagnosis, mean blood pressure, lipoprotein(a), and apolipoprotein B did not correlate with albumin excretion rate, after controlling for other variables. Our findings highlight the continuing need for strategies to prevent smoking in this age group.

Twenty-five children aged 2-14 years (mean age 8.39 +/- 0.78 years) were studied prospectively during the first year after the diagnosis of type 1 diabetes. Of their clinical and metabolic features at diagnosis, only age showed a significant independent relationship with endogenous C-peptide production during the first year. Age was correlated with higher values for basal and stimulated plasma C-peptide at 7-14 days after diagnosis, at 6 months and at 12 months. At diagnosis, age was also associated with a higher value for HbA1c and a lower prevalence of insulin antibodies. C-peptide production peaked at 3 months and thereafter declined. Mean HbA1c and insulin requirement were both minimal at 6 months. At diagnosis, there were significant inverse relationships between basal C-peptide production and both insulin dose and HbA1c and between stimulated C-peptide production and HbA1c. Basal and stimulated C-peptide production were inversely related to insulin dose at 6 and 12 months. Stimulated C-peptide was higher at 12 months in children retaining islet cell antibodies. These findings confirm the importance of age as a predictor of residual beta-cell function in type 1 diabetes and indicate that older children present clinically following a slower course of beta cell destruction.