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Aims: Pancreatic islet allotransplantation is an effective therapy for type 1 diabetes mellitus, restoring glycaemic control and hypoglycaemic awareness in patients with recurrent severe hypoglycaemia. Insulin independence following transplant is being increasingly reported; however, this is not a primary endpoint in the UK. Having surpassed 10 years of islet transplantation in Scotland, we aimed to evaluate the impact of insulin independence following transplant on metabolic outcomes and graft survival. Methods: We conducted a retrospective analysis on data collected prospectively between 2011 and 2022. Patients who underwent islet transplantation in Scotland up to the 31st January 2020 were included. Primary endpoint was graft survival (stimulated C‐peptide >50 pmol/L). Secondary endpoints included GOLD score, HbA1c, C‐peptide and insulin requirement. Outcomes were compared between patients who achieved insulin independence at any point following transplant versus those who did not. Results: 60 patients were included. 74.5% experienced >50 severe hypoglycaemic episodes in the year preceding transplant. There was a 55.0% decrease in insulin requirement following transplant and 30.0% achieved insulin independence. Mean graft survival time was 9.0 years (95% CI 7.2–10.9) in patients who achieved insulin independence versus 4.4 years (95% CI 3.4–5.3) in patients who did not. Insulin independence was associated with significantly improved graft function, glycaemic control and hypoglycaemic awareness at 1 year. Conclusions: This is the largest UK single‐centre study on islet transplant to date. Our findings demonstrate significantly improved outcomes in patients who achieved insulin independence following islet transplantation. [ABSTRACT FROM AUTHOR]

Aims: Most people with Type 1 diabetes have low levels of persistent endogenous insulin production. The Diabetes Control and Complications Trial showed that close to diagnosis preserved endogenous insulin was associated with lower HbA1c, hypoglycaemia and complication rates, when intensively treated. We aimed to assess the clinical impact of persistent C‐peptide on rate of hypoglycaemia and HbA1c in those with long duration (> 5 years) Type 1 diabetes. Methods: We conducted a cross‐sectional case–control study of 221 people (median age 24 years) with Type 1 diabetes. We confirmed ongoing endogenous insulin secretion by measuring C‐peptide after a mixed‐meal tolerance test. We compared self‐reported hypoglycaemia (n = 160), HbA1c, insulin dose and microvascular complications (n = 140) in those with preserved and low C‐peptide. Results: Stimulated median (IQR) C‐peptide was 114 (43, 273) pmol/l and < 3 (< 3, < 3) pmol/l in those with preserved and low C‐peptide respectively. Participants with preserved C‐peptide had lower reported monthly rates of hypoglycaemia, with 21% fewer symptomatic episodes, 5.9 vs. 7.5 [incidence rate ratio (IRR) 0.79, P = 0.001], and 65% fewer asymptomatic episodes, 1.0 vs. 2.9 (IRR 0.35, P < 0.001). Those with preserved C‐peptide had a lower insulin dose (0.68 vs. 0.81 units/kg, P = 0.01) but similar HbA1c (preserved 69 vs. low 67 mmol/mol, P = 0.06). Conclusions: Adults with Type 1 diabetes and preserved endogenous insulin production receiving usual care in the UK have lower daily insulin doses and fewer self‐reported hypoglycaemic episodes, but no difference in HbA1c. This is consistent with non‐intensive treatment in previous studies, and suggests a need to consider therapy intensification to gain full benefit of preserved endogenous insulin. What's new?: Little is known about the clinical impact of persistent C‐peptide in long‐duration Type 1 diabetes.We found that in adults with long‐duration Type 1 diabetes, persistent C‐peptide was associated with reduced self‐reported hypoglycaemia and insulin dose but was not associated with reduced HbA1c.This suggests that individuals with persistent C‐peptide receiving routine care are potentially undertreated.Routinely testing C‐peptide and subsequently setting personalized targets for treatment intensification in adults with persistent C‐peptide may improve glycaemic control and complication rates in this group. [ABSTRACT FROM AUTHOR]

Supplemental digital content is available in the text. Purpose: Exposure to high altitude has been shown to enhance both glucose and lipid utilization depending on experimental protocol. In addition, high and low blood glucose levels have been reported at high altitude. We hypothesized that gradual ascent to high altitude results in changes in glucose levels in healthy young adults. Methods: Twenty-five adult volunteers, split into two teams, took part in the British Services Dhaulagiri Medical Research Expedition completing 14 d of trekking around the Dhaulagiri circuit in Nepal reaching a peak altitude of 5300 m on day 11 of the trek. Participants wore blinded continuous glucose monitors (CGM) throughout. Blood samples for C-peptide, proinsulin, and triacylglycerides were taken at sea level (United Kingdom) and in acclimatization camps at 3600, 4650, and 5120 m. Energy intake was determined from food diaries. Results: There was no difference in time spent in hypoglycemia stratified by altitude. Nocturnal CGM readings (2200–0600 h) were chosen to reduce the short-term effect of physical activity and food intake and showed a significant ( P < 0.0001) increase at 3600 m (5.53 ± 0.22 mmol·L−1), 4650 m (4.77 ± 0.30 mmol·L−1), and 5120 m (4.78 ± 0.24 mmol·L−1) compared with baseline altitude 1100 m (vs 4.61 ± 0.25 mmol·L−1). Energy intake did not differ by altitude. Insulin resistance and beta-cell function, calculated by homeostatic model assessment, were reduced at 3600 m compared with sea level. Conclusions: We observed a significant increase in nocturnal CGM glucose at 3600 m and greater despite gradual ascent from 1100 m. Taken with the changes in insulin resistance and beta-cell function, it is possible that the stress response to high altitude dominates exercise-enhanced insulin sensitivity, resulting in relative hyperglycemia. [ABSTRACT FROM AUTHOR]

Aims To demonstrate that analysis of urinary C-peptide across multiple study sites in the context of an intervention trial ( DEFEND-2) is a viable alternative to mixed meal testing and delivers results that correlate to mixed meal testing estimation of endogenous insulin production. Methods Second morning void urine was collected for analysis and was available from 161 subjects at baseline (55 placebo, 106 otelixizumab), and 146 subjects (47 placebo, 99 otelixizumab) at month 12. Urinary C-peptide concentration was corrected for urinary creatinine [urinary C-peptide/creatinine ratio ( UCPCR)] and serum C-peptide from the mixed meal tolerance test was calculated using area under the plasma concentration-time curve ( AUC) normalized over 120 min. The correlation between mixed meal stimulated C-peptide AUC (mmol/l/min) and UCPCR (nmol/mmol), as well as the correlation between insulin use ( IU/kg), and HbA1c (%) with UCPCR, was determined. Results UCPCR and mixed meal testing C-peptide AUC were correlated, with a correlation coefficient of 0.4172. UCPCR was not correlated with exogenous insulin use ( r = -0.089) or with HbA1c ( r = -0.032). Conclusions Urinary C-peptide estimation should be considered as a measure of endogenous insulin production in future Type 1 diabetes mellitus outcome trials. A change in the timing for urine collection (to 120 min post standard meal) may provide a tighter correlation to C-peptide measured via a traditional mixed meal test. [ABSTRACT FROM AUTHOR]

Aims To determine if urine C-peptide/creatinine ratio is a useful tool for monitoring β-cell function in new-onset Type 1 diabetes. Methods Data were obtained from a prospective immunomodulation study in people with Type 1 diabetes ≤ 3 months from diagnosis, with a standard mixed-meal tolerance test and measurement of urine C-peptide/creatinine ratio carried out at 0, 3, 6, 9 and 12 months. The change in the insulin-dose-adjusted HbA1c level was also correlated with the change in serum/urine C-peptide level during the 12-month follow-up period. Results A significant reduction in urine C-peptide/creatinine ratio, measured after a mixed-meal, was reached at 9 months (−45.4%), whilst the reduction in stimulated serum C-peptide level reached significance after 3 months (−54.7%) in placebo-treated participants. Neither change in stimulated serum C-peptide nor change in urine C-peptide level correlated with each other, and nor did change in insulin-dose-adjusted HbA1c level in the first 6 months, but all measures correlated significantly in the second half of the 12-month follow-up period. Conclusion Mixed-meal-stimulated urine C-peptide/creatinine ratio was similar to, although less sensitive than, stimulated serum C-peptide level in monitoring β-cell function during the first year after diagnosis. Because the former is significantly less invasive, it warrants inclusion in further studies in Type 1 diabetes and may represent an attractive alternative outcome measure in cohort studies and in children. [ABSTRACT FROM AUTHOR]

Background: Cereal crops, particularly wheat, are a major dietary source of starch, and the bioaccessibility of starch has implications for postprandial glycemia. The structure and properties of plant foods have been identified as critical factors in influencing nutrient bioaccessibility; however, the physical and biochemical disassembly of cereal food during digestion has not been widely studied. Objectives: The aims of this study were to compare the effects of 2 porridge meals prepared from wheat endosperm with different degrees of starch bioaccessibility on postprandial metabolism (e.g., glycemia) and to gain insight into the structural and biochemical breakdown of the test meals during gastroileal transit. Design: A randomized crossover trial in 9 healthy ileostomy participants was designed to compare the effects of 55 g starch, provided as coarse (2-mm particles) or smooth (,0.2-mm particles) wheat porridge, on postprandial changes in blood glucose, insulin, C-peptide, lipids, and gut hormones and on the resistant starch (RS) content of ileal effluent. Undigested food in the ileal output was examined microscopically to identify cell walls and encapsulated starch. Results: Blood glucose, insulin, C-peptide, and glucose-dependent insulinotropic polypeptide concentrations were significantly lower (i.e., 33%, 43%, 40%, and 50% lower 120-min incremental AUC, respectively) after consumption of the coarse porridge than after the smooth porridge (P , 0.01). In vitro, starch digestion was slower in the coarse porridge than in the smooth porridge (33% less starch digested at 90 min, P , 0.05, paired t test). In vivo, the structural integrity of coarse particles (w2 mm) of wheat endosperm was retained during gastroileal transit. Microscopic examination revealed a progressive loss of starch from the periphery toward the particle core. The structure of the test meal had no effect on the amount or pattern of RS output. Conclusion: The structural integrity of wheat endosperm is largely retained during gastroileal digestion and has a primary role in influencing the rate of starch amylolysis and, consequently, postprandial metabolism. This trial was registered at isrctn.org as ISRCTN40517475. [ABSTRACT FROM AUTHOR]

OBJECTIVE Small studies using ultrasensitive C-peptide assays suggest endogenous insulin secretion is frequently detectable in patients with long-standing type 1 diabetes (T1D), but these studies do not use representative samples. We aimed to use the stimulated urine C-peptide-to-creatinine ratio (UCPCR) to assess C-peptide levels in a large cross-sectional, population-based study of patients with T1D. RESEARCH DESIGN AND METHODS We recruited 924 patients from primary and secondary care in two U.K. centers who had a clinical diagnosis of T1D, were under 30 years of age when they received a diagnosis, and had a diabetes duration of >5 years. The median age at diagnosis was 11 years (interquartile range 6-17 years), and the duration of diabetes was 19 years (11-27 years). All provided a home postmeal UCPCR, which was measured using a Roche electrochemiluminescence assay. RESULTS Eighty percent of patients (740 of 924 patients) had detectable endogenous C-peptide levels (UCPCR >0.001 nmol/mmol). Most patients (52%, 483 of 924 patients) had historically very low undetectable levels (UCPCR 0.0013-0.03 nmol/mmol); 8% of patients (70 of 924 patients) had a UCPCR ≥0.2 nmol/mmol, equivalent to serum levels associated with reduced complications and hypoglycemia. Absolute UCPCR levels fell with duration of disease. Age at diagnosis and duration of disease were independent predictors of C-peptide level in multivariate modeling. CONCLUSIONS This population-based study shows that the majority of long-duration T1D patients have detectable urine C-peptide levels. While the majority of patients are insulin microsecretors, some maintain clinically relevant endogenous insulin secretion for many years after the diagnosis of diabetes. Understanding this may lead to a better understanding of pathogenesis in T1D and open new possibilities for treatment. [ABSTRACT FROM AUTHOR]

The article presents abstracts on medical topics which include the risk assessment for type 2 diabetes diagnosis, effectiveness of random non-fasting c-peptide for endogenous insulin secretion measurement, and weight loss therapy in diabetic patients.

The article presents the discussion on Type 1 diabetes. Topics include analysis of pancreas pathology and insulitis in young people with recent-onset type 1 diabetes; individuals with long-duration type 1 diabetes demonstrating altered time-course responses of markers of bone resorption; and C-peptide decline following a similar biphasic pattern in both Great Britain and Indian type 1 diabetes patients.

The article presents medical abstracts including the determination of inconsistencies in admissions for secondary care diabetes, as well as its cost implications, the use of complementary markers in the evaluation of glyceamic control in diabetic patients with chronic kidney disease (CKD) who undergo treatment of iron or erythropoiesis stimulating agent, and the use of Urine C-peptide creatinine ratio to determine maturity onset diabetes of the young (MODY) and type 2 diabetes in children.