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Aims/hypothesis: Diabetes diagnosed at <6 months of age is usually monogenic. However, 10–15% of affected infants do not have a pathogenic variant in one of the 26 known neonatal diabetes genes. We characterised infants diagnosed at <6 months of age without a pathogenic variant to assess whether polygenic type 1 diabetes could arise at early ages. Methods: We studied 166 infants diagnosed with type 1 diabetes at <6 months of age in whom pathogenic variants in all 26 known genes had been excluded and compared them with infants with monogenic neonatal diabetes (n = 164) or children with type 1 diabetes diagnosed at 6–24 months of age (n = 152). We assessed the type 1 diabetes genetic risk score (T1D-GRS), islet autoantibodies, C-peptide and clinical features. Results: We found an excess of infants with high T1D-GRS: 38% (63/166) had a T1D-GRS >95th centile of healthy individuals, whereas 5% (8/166) would be expected if all were monogenic (p < 0.0001). Individuals with a high T1D-GRS had a similar rate of autoantibody positivity to that seen in individuals with type 1 diabetes diagnosed at 6–24 months of age (41% vs 58%, p = 0.2), and had markedly reduced C-peptide levels (median <3 pmol/l within 1 year of diagnosis), reflecting rapid loss of insulin secretion. These individuals also had reduced birthweights (median z score −0.89), which were lowest in those diagnosed with type 1 diabetes at <3 months of age (median z score −1.98). Conclusions/interpretation: We provide strong evidence that type 1 diabetes can present before the age of 6 months based on individuals with this extremely early-onset diabetes subtype having the classic features of childhood type 1 diabetes: high genetic risk, autoimmunity and rapid beta cell loss. The early-onset association with reduced birthweight raises the possibility that for some individuals there was reduced insulin secretion in utero. Comprehensive genetic testing for all neonatal diabetes genes remains essential for all individuals diagnosed with diabetes at <6 months of age. [ABSTRACT FROM AUTHOR]

Type 1 diabetes, perhaps more than any other chronic condition, demands self-management, upon which depend long-term outcomes. Nearly all young people turn to apps, websites and social media as the natural first solution to searches for information or to connect with others. Clinicians need to understand the Internet and all the other sources of information that patients may use in constructing their understanding of, and in self-managing, their condition. DSNs now generally work in partnership with patients, and accept that they may learn much from them. This article describes how young people with diabetes have been using apps and the Internet in an effort to help DSNs better engage with this online way of life, and to suggest ways in which they can better stay informed. [ABSTRACT FROM AUTHOR]

Objective: Insulin secretion in sulfonylurea-treated KCNJ11 permanent neonatal diabetes mellitus (PNDM) is thought to be mediated predominantly through amplifying non-K ATP -channel pathways such as incretins. Affected individuals report symptoms of postprandial hypoglycemia after eating protein/fat-rich foods. We aimed to assess the physiological response to carbohydrate and protein/fat in people with sulfonylurea-treated KCNJ11 PNDM., Research Design and Methods: 5 adults with sulfonylurea-treated KCNJ11 PNDM and five age, sex and body mass index-matched controls without diabetes had a high-carbohydrate and high-protein/fat meal on two separate mornings. Insulin(i) and glucose(g) were measured at baseline then regularly over 4 hours after the meal. Total area under the curve (tAUC) for insulin and glucose was calculated over 4 hours and compared between meals in controls and KCNJ11 cases., Results: In controls, glucose values after carbohydrate and protein/fat were similar (median glucose tAUC 0-4h 21.4 vs 19.7 mmol/L, p=0.08). In KCNJ11 cases glucose levels were higher after carbohydrate than after protein/fat (median glucose tAUC 0-4h 58.1 vs 31.3 mmol/L, p=0.04). These different glycemic responses reflected different patterns of insulin secretion: in controls, insulin secretion was greatly increased after carbohydrate versus protein/fat (median insulin tAUC 0-4h 727 vs 335 pmol/L, p=0.04), but in KCNJ11 cases insulin secretion was similar after carbohydrate and protein/fat (median insulin tAUC 0-4h 327 vs 378 pmol/L, p=0.50)., Conclusions: Individuals with sulfonylurea-treated KCNJ11 PNDM produce similar levels of insulin in response to both carbohydrate and protein/fat meals despite carbohydrate resulting in much higher glucose levels and protein/fat resulting in relatively low glucose levels. This suggests in an inability to modulate insulin secretion in response to glucose levels, consistent with a dependence on non-K ATP pathways for insulin secretion., Trial Registration Number: NCT02921906., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.)