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C-peptide in juvenile diabetics beyond the postinitial remission period. Relation to clinical manifestations at onset of diabetes, remission and diabetic control.

A group of 58 diabetics, age 6-17 years and with a duration of diabetes of 3-14 years was studied in order to show whether the nature of the clinical manifestations and the treatment at the onset of the disease are related to the subsequent C-peptide production and also whether remaining C-peptide production is related to better diabetic control. The relations between a number of clinical and laboratory variables were analysed including the degree of ketosis and the insulin dose given at onset of diabetes, the incidence of postinitial remission period, the fasting C-peptide level after the remission period, the level of insulin antibodies and the actual diabetic control expressed as the degree of glucosuria in the patients' urine tests at home. Multiple regression analysis was the main method used. Postinitial remission was positively correlated to initial insulin dose and negatively correlated to duration of ketonuria at onset. C-peptide, which was found in 24.1% of the patients was positively correlated to age at onset and initial insulin dose, but negatively correlated to ketonuria at onset. Diabetic control was positively correlated to insulin dose at onset and to C-peptide level, but negatively correlated to insulin antibodies. It could further be shown that patients who had received a more vigorous treatment immediately at onset had both a higher incidence of postinitial remission and a better diabetic control. The results suggest that an early diagnosis followed by rapid normalization of the metabolism at the onset of juvenile diabetes increase the possibility of preservation of some of the endogenous insulin production, which seems to facilitate diabetic control.

Adolescent

The management of type 1 diabetes in adults. The updated 2026 consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD).

This 2026 consensus report from the European Association for the Study of Diabetes (EASD) and the American Diabetes Association (ADA) builds on the 2021 consensus report to provide guidance for managing type 1 diabetes in adults. Reflecting the rapid advances in the field, this update places particular emphasis on the integration of new technologies, while all sections have been revised to incorporate new evidence, advances in clinical practice and novel therapies, including interventions to delay the onset of stage 3 type 1 diabetes. It also broadens its scope to screening for long-term diabetes complications, and the management of obesity and cardiovascular risk factors. Psychosocial care and diabetes self-management education and support (DSMES) remain key elements. The report was developed using the Accurate Consensus Reporting Document (ACCORD) framework. The guidance aligns with the current ADA 'Standards of Care in Diabetes' (Standards of Care) and relevant EASD and ADA documents and aims to support clinicians globally in delivering high-quality, personalised care for adults with type 1 diabetes, with recommendations that can be adapted across diverse healthcare systems and resource settings.

Adjunctive therapy

The Heterogeneity of Type 1 Diabetes: Implications for Pathogenesis, Prevention, and Treatment-2024 Diabetes, Diabetes Care, and Diabetologia Expert Forum.

This article summarizes the current understanding of the heterogeneity of type 1 diabetes from a June 2024 international Expert Forum organized by the editors of Diabetes, Diabetes Care, and Diabetologia. The Forum reviewed key factors contributing to the development and progression of type 1 diabetes and outlined specific, high-priority research questions. Knowledge gaps were identified, and, notably, opportunities to harness disease heterogeneity to develop personalized therapies were outlined. Herein, we summarize our discussions and review the heterogeneity of genetic risk and immunologic and metabolic phenotypes that influence and characterize type 1 diabetes progression (presented as a palette of risk factors). We discuss how these age-related factors determine disease aggressiveness (along gradients) and describe how variable immunogenetic pathways aggregate (into networks) to affect β-cell and other pancreatic pathologies to cause clinical disease at different ages and with variable severity (described as disease-related thresholds). Heterogeneity of pathogenesis and clinical severity opens avenues to prevention and intervention, including the potential of disease-modifying immunotherapy and islet cell replacement. We conclude with a call for 1) continued research to identify more factors contributing to the disease, both overall and in specific subgroups; 2) investigations focusing on both individuals who surpass metabolic and immune thresholds and develop diabetes and those who remain disease free with the same level of immunogenetic risk; and 3) efforts to identify where the current type 1 diabetes staging system may fall short and determine how it can be improved to capture and leverage heterogeneity in prevention and intervention strategies.

Humans

[Pathogenesis of diabetic microangiopathy. Protein and basement membrane synthesis in isolated kidney glomeruli of diabetic and non-diabetic rats].

In incubation experiments with isolated glomeruli, an increased synthesis of protein and basement membranes was detected in streptozotocin-diabetic rats compared to metabolically healthy controls. Chemical analysis of isolated basement membranes and incorporation studies did not give any indication of enhanced hydroxylation of lysine in the diabetic membrane. Different glucose concentration in the incubation medium and insulin in vitro did not influence protein and basement membrane synthesis of non-diabetic glomeruli. On the other hand, in diabetic glomeruli the synthetic activity depends on glucose concentration. Insulin had a stimulatory effect on protein and basement membrane synthesis diminished at lower glucose concentration and did not inhibit the increased synthetic activity demonstrated at higher glucose concentration. Therefore, these results may be attributable to an energy deficit of incubated glomeruli and not to a lower glucose stimulation of synthesis. By treatment of diabetic rats with insulin in vivo the synthetic activity was not affected by brief normalization of blood sugar. Insulin treatment from the beginning of diabetes only lead to a normalization of protein synthesis in moderate metabolic control. On the other hand, a rise of basement membrane synthesis could only be prevented by strict metabolic control of the rats. These results show that basement membrane synthesis reacts more sensitively to the diabetic situation than overall protein synthesis. Insulin deficiency does not appear to be one of the factors directly influencing basement membrane synthesis.

Animals

Leakage of fluorescein: first sign of juvenile diabetic retinopathy. Role of diabetic control and of duration of diabetes.

In order to ascertain the first vascular lesions responsible for juvenile diabetic retinopathy, 408 fluorescein angiographies were performed in 114 diabetic children and adolescents whose diabetes became clinically apparent before the age of 14 years. Compared with regular ophthalmoscopy, fluorescein angiography doubles the frequency of the diagnosis of incipient retinopathy. In addition to the classical diabetic lesions, fluorescein leakages are demonstrated in 50% of diabetic eyes with initial retinopathy. They probably reflect early changes in capillary permeability. They appear often before microaneurysms. Duration of diabetes as well as insufficient and poor metabolic control considerably increase the frequency of retinopathy.

Adolescent

The Management of Type 1 Diabetes in Adults. The Updated 2026 Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD).

This 2026 consensus report from the European Association for the Study of Diabetes (EASD) and the American Diabetes Association (ADA) builds on the 2021 consensus report to provide guidance for managing type 1 diabetes in adults. Reflecting the rapid advances in the field, this update places particular emphasis on the integration of new technologies, while all sections have been revised to incorporate new evidence, advances in clinical practice, and novel therapies, including interventions to delay the onset of stage 3 type 1 diabetes. It also broadens its scope to screening for long-term diabetes complications, and the management of obesity and cardiovascular risk factors. Psychosocial care and diabetes self-management education and support (DSMES) remain key elements.

Journal Article

Study of bladder function in patients with prediabetes, latent diabetes, recent onset diabetes and juvenile diabetes.

We have studied the vesical function in 4 prediabetics, 11 latent diabetics, 11 recent onset insulin dependent diabetics and a control group of 6 normal individuals. We found in recent onset of diabetics disturbances of cystometric parameters in a statistically significant proportion. This proportion increases with the evolution of diabetes. The difference in sensitivity to cold water that we found betwee SDB and NBD was statistically significant, so the denomination 'hyposensitive bladder' is well applied in this fist phase of vesical neuropathy.

Adolescent

Four risk factors for severe visual loss in diabetic retinopathy. The third report from the Diabetic Retinopathy Study. The Diabetic Retinopathy Study Research Group.

The Diabetic Retinopathy Study (DRS) Research Group has so far identified four retinopathy factors that increase the two-year risk of developing severe visual loss. The risk grows as the number of risk factors increases. Eyes with three or more risk factors (eyes with "high-risk characteristics") are at a much higher risk than eyes with two or fewer factors. The DRS protocol was changed in 1976 to require consideration of treatment for these "high-risk" eyes.

Collateral Circulation

[Diabetic polyneuropathy. 3. Electroneurographic findings in diabetics and their relationships to age and duration of diabetes].

Nerve conduction velocities were determined in patients with diabetes mellitus: motor conduction of the median nerve in 778 patients, sensory conduction of the median nerve in 680 patients and motor conduction of the tibial nerve in 745 patients. In 40.9% out of 778 patients at least one of the three nerve conduction velocities were found within pathological ranges. 30.4% of 227 patients below 19 years of age in whom the duration of the disease did not exceed four years exhibited at least one delayed nerve conduction velocity. Clinical signs of polyneuropathy in children and in adolescents below 19 years of age are rare (0.6%). In contrast delayed nerve conduction velocities were found in 29.4%. Metabolic disturbance of peripheral nerve function is assumed to be responsible in these patients, for angiopathy in children and adolescents is very rare too.

Adolescent

Large-scale multiethnic electronic health record resource for diabetes complications research: the North West London Diabetes Cohort (NWLDC) - cohort profile.

PURPOSE: The North West London Diabetes Cohort is established to provide systematic characterisation of a large diabetes population as a foundation for complications research and prognostic modelling. Many predictive modelling studies neglect the essential descriptive characterisation of underlying cohorts, focusing narrowly on model accuracy. This cohort profile addresses this gap by comprehensively describing the demographic composition, clinical characteristics and complication incidence patterns. The notably diverse, multiethnic population enables examination of ethnic disparities and supports future development of reliable prognostic models and evidence-based prevention strategies for diabetes complications. PARTICIPANTS: At baseline, 337 271 patients with diabetes were identified. It includes 279 067 patients with type 2 diabetes, 17 638 with type 1 diabetes, 33 590 with gestational diabetes and 6916 with unspecified diabetes. The earliest diabetes diagnosis dates to January 1932, with data updated to 27 May 2025. FINDINGS TO DATE: This cohort profile describes baseline characteristics of patients with comprehensive data collected on demographics (age, sex, Deprivation Index, ethnicity), clinical measures (glycated haemoglobin, body mass index, blood pressure, lipids and estimated glomerular filtration rate) and 14 major diabetes complications tracked longitudinally. Key findings for patients with type 2 diabetes reveal diabetic retinopathy as the most common complication (74.6 per 1000 person-years), followed by hypertension (51.0) and kidney disease (31.4). Cumulative incidence analyses using the Aalen-Johansen estimator, which accounts for mortality as a competing risk, demonstrated significant ethnic disparities, with black, Asian, mixed and other ethnic groups showing elevated risk compared with white patients. Time-varying Cox models identified strong clustering between cardiovascular and renal complications, confirming a cardiometabolic-renal syndrome. Mental health conditions (depression and anxiety) were prevalent throughout the disease timeline, occurring both before and after diabetes diagnosis. FUTURE PLANS: This cohort will be used as a platform for developing and validating prognostic models for diabetes complications, enabling risk stratification and targeted interventions. Future work will incorporate medication data to refine diabetes type classification, examine the effectiveness of antidiabetic medications in preventing different complications and address demographic differences in prognostic model performance and prediction accuracy. To better characterise lifestyle, further interrogation of electronic health record data will examine recording of advice given, including dietary advice, referral to weight management schemes and presence of alcohol consumption codes.

Humans

Actions of salbutamol in late pregnancy: plasma cyclic AMP, insulin and C-peptide, carbohydrate and lipid metabolites in diabetic and non-diabetic women.

Salbutamol was administered intravenously in dose increasing from 3.75 to 22.5 microgram/min to 5 non-diabetic and 7 diabetic women in the last trimester of pregnancy. In diabetic as well as non-diabetic women the diastolic blood pressure fell progressively with increasing doses, and the systolic BP and heart rate increased at doses above 7.5 microgram/min. The effect of fetal heart rate was less pronounced than the effect on maternal heart rate. Cyclic AMP levels in plasma were similar in non-diabetic and diabetic women before salbutamol. Twenty min following 3.75 microgram/min a significant increase was seen in both groups. The peak increase (3-5 fold) was higher in the diabetic than in the non-diabetic women. Plasma insulin and C-peptide levels rose in a dose-dependent manner in the non-diabetic and four of the diabetic women. However, in three of the diabetic women the insulin level was unaffected by salbutamol and C-peptide was almost undetectable. Plasma concentrations of glucose, glycerol, NEFA and 3-HB were higher in the diabetics than in the non-diabetics before salbutamol and the elevations induced by salbutamol were also significantly larger in the diabetic women. The present data show that salbutamol in doses employed clinically may cause pronounced metabolic effects, especially in diabetic women, and it is suggested that when intravenous infusion of salbutamol is given to pregnant diabetic women not only cardiovascular but also some metabolic variable such as glucose should be carefully monitored.

Adult

Pancreatic islet-cell antibodies in diabetes mellitus correlated with the duration and type of diabetes, coexistent autoimmune disease, and HLA type.

In a study of 972 patients with diabetes mellitus, humoral pancreatic islet-cell antibodies (I.C.Ab.) were detected in highest prevalence in insulin-treated diabetics with (38 per cent) and without (22 per cent) associated overt organ-specific autoimmune disease (A.I.D.) where consideration was not given to the duration of diabetes. They were also detected in 8 per cent of diabetics treated with oral hypoglycemic agents (O.H.A.), but not in diabetics requiring diet alone and in only 0.5 per cent of 434 control subjects. Six per cent of 522 patients with overt organ-specific A.I.D. but not diagnosed to be diabetic had I.C.Ab.s. I.C.Ab.s were present in the sera of 2 per cent of 157 first-degree relatives of I.C.Ab.-positive subjects. In insulin-treated diabetics and, to a lesser extent, in diabetics not requiring insulin, the prevalence of humoral I.C.Ab. was strongly dependent of the duration of the diabetes, being 60 per cent during the first year from diagnosis in the insulin-treated group and falling to 20 per cent at two to five years and to 5 per cent at 10-20 years. The prevalence of I.C.Ab. in insulin-treated diabetics showed no correlation with the patient's age at the time of testing when the duration of diabetes was taken into account. Diabetics who did not require insulin for treatment but who were I.C.Ab.-positive showed a significant tendency to subsequently require insulin and to have a higher prevalence of other autoantibodies than insulin-independent diabetics who were I.C.Ab.-negative. Persistence of I.C.Ab. for more than five years from diagnosis of diabetes was associated with coexistent overt organ-specific A.I.D. and with HLA-B8, A1, and A1 + B8.

Adult

Divergent autoimmune genetic landscapes in diabetic and non-diabetic individuals.

BACKGROUND: Type 2 diabetes (T2D) and autoimmune diseases are complex disorders shaped by genetic, immunological, and environmental factors. However, differences in genetic susceptibility to autoimmune disorders between diabetic and non-diabetic individuals remain poorly understood, particularly within the Indian population. This study aimed to compare polygenic susceptibility to multiple autoimmune diseases between individuals with and without T2D from Gujarat, India. RESULTS: Polygenic risk scores were evaluated for eleven autoimmune diseases in 474 individuals, including 99 diabetics and 375 non-diabetics. Significant differences were observed for systemic lupus erythematosus and rheumatoid arthritis. Individuals with diabetes showed a higher genetic risk for systemic lupus erythematosus, whereas non-diabetic individuals exhibited a higher genetic risk for rheumatoid arthritis. Pathway enrichment analysis of disease-associated genetic variants revealed significant involvement of immune-related pathways, including antigen processing and presentation, T-helper cell differentiation, and immune responses to viral infections. CONCLUSIONS: The findings reveal disease-specific differences in genetic susceptibility to autoimmune disorders between diabetic and non-diabetic individuals. These results highlight the complex immunogenetic relationship between type 2 diabetes and autoimmune diseases and provide insight into shared and distinct immune pathways within an Indian population. Such information may support future efforts in risk stratification and precision medicine approaches for immune-related comorbidities in diabetes.

Humans

Glomerulopathy in rats with streptozotocin diabetes. Accumulation of glomerular basement membrane analogous to human diabetic nephropathy.

Glomeruli from streptozotocin-diabetic and age-matched nondiabetic rats were quantitatively isolated by a differential sieving technique. The insoluble glomerular basement membranes were purified following sonic disruption in the presence of proteolytic inhibitors. The yield of glomeruli and of glomerular basement membrane relative to the amount of renal cortex and the body weight of the animals, as well as the calculated amount of basement membrane per glomerulus, were all significantly greater in diabetic rats when compared to non-diabetic controls. Glomerular basement membranes from normal and diabetic rats were solubilized by reduction and denaturation in the presence of SDS and subjected to agarose gel analysis. About 65% of both normal and diabetic basement membrane was solubilized by this procedure, and the elution profiles of non-diabetic and diabetic preparations were similar. These results suggest that rat renal basement membrane is qualitatively similar but quantitatively increased in streptozotocin-diabetes. Since glomerular enlargement and accumulation of basement membrane are characteristic of human diabetic nephropathy, the findings also suggest that the streptozotocin-diabetic rat is an appropriate animal model for studies relating to the pathogenesis of this complication of diabetes.

Animals

The intestinal brush border membrane in diabetes. Studies of sucrase-isomaltase metabolism in rats with streptozotocin diabetes.

Diabetes stimulates the functional activity of the intestinal brush border membrane with enhancement of both hydrolytic enzyme activity and membrane transport systems. To determine the mechanism of this effect, we studied the effects of streptozotocin diabetes on the metabolism of one membrane protein, sucrase-isomaltase, which increases its activity in diabetes. The protein was purified and an antiserum prepared. Sucrase-isomaltase from control and diabetic rats was immunologically identical as shown by Ouchterlony double-diffusion analysis of papain-solubilized mucosal proteins. The increase in sucrase enzyme activity in diabetic animals (31.0+/-1.4 U SEM 5 days after streptozotocin vs. 13.1+/-1.0 in controls) was the consequence of increased enzyme protein and not an alteration in catalytic efficiency as demonstrated by quantitative immunoprecipitin reactions. To account for increased sucrase-isomaltase protein in diabetes we studied papain-solubilized mucosal proteins labeled by injection of [(14)C]carbonate and [(14)C]leucine and analyzed incorporation into sucrase-isomaltase protein (anti-serum precipitable) and total protein (trichloroacetic acid precipitable). We found that diabetes did not affect the decay of labeled total protein, but prolonged the decay of labeled sucrase-isomaltase. t((1/2)) of sucrase-isomaltase was 4.4 h in control animals after [(14)C]carbonate injection and 8.8 and 10.2 h, respectively, 2 and 5 days after induction of streptozotocin diabetes. We obtained similar results in experiments with [(14)C]leucine with diabetes increasing t((1/2)) from 6 to 13.6 h. Diabetes did not appear to increase the rate of addition of sucrase-isomaltase to the brush border membrane, since it did not affect the 10- and 60-min incorporations of isotope into sucrase-isomaltase protein relative to incorporation into total protein and did not alter rate constants for synthesis calculated from the t((1/2)) and the change in enzyme mass over time.Thus, enhanced sucrase activity in the diabetic animal is the consequence of an increase in sucrase-isomaltase protein which develops because of a decrease in its rate of degradation.

Animals

Identification of circulating miRNA alterations in diabetes patients excluding periodontitis effects: insights into target gene downregulation in diabetic complications.

BACKGROUND: Diabetes mellitus (DM) induces systemic complications through chronic metabolic dysregulation. Circulating exosomal microRNAs (miRNAs) are emerging as key regulators of post-transcriptional gene expression and may drive diabetes-associated pathologies. Although miRNAs have been widely studied in diabetes, the characterization of PD-independent miRNA signatures across tissues remains limited. This study aimed to identify DM-specific miRNA alterations and their contribution to systemic metabolic dysfunction independent of PD. METHODS: Exosomes were isolated from plasma samples, and small RNA sequencing was performed to identify differentially expressed miRNAs (DE-miRs) using the limma R package. Predicted target genes were identified using TargetScan and validated through bulk RNA sequencing datasets from four tissues-foot, kidney, pancreas, and retina. Differentially expressed genes (DEGs) were analyzed, followed by Gene Ontology Biological Process (GOBP) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment to elucidate diabetes-related mechanisms. RESULTS: We identified 9 upregulated and 6 downregulated DE-miRs specific to the diabetic group. TargetScan predicted 216 upregulated and 64 downregulated target genes. Functional validation revealed that these genes were enriched in pathways related to glucose metabolism, cellular stress response, and tissue repair. Notably, SREK1 and GLIPR1 were commonly detected across all four tissues, suggesting potential systemic regulators of diabetes-related complications. CONCLUSION: This study suggests that circulating exosomal miRNAs, independent of periodontitis, may function as systemic regulators in diabetes. Unlike previous studies, which did not distinguish co-morbid periodontitis, we specifically defined PD-independent miRNA signatures and validated their cross-organ regulatory effects on target genes. Our results revealed a cross-organ miRNA-mRNA regulatory network and identified common regulatory targets. These findings provide insights into both systemic and organ-specific mechanisms underlying diabetic complications and highlight the potential of miRNAs as biomarkers and therapeutic targets.

Humans

[Autoradiographic studies on protein metabolism and histochemical demonstration of the brain zinc content in diabetes mellitus. 1. Comparison in experimental streptozotocin-induced diabetes].

By application of streptozotocin diabetes mellitus is induced in rats: 40 mg/kg body weight streptozotocin produce a fairly serious diabetes with minimal ketosis, 125 mg/kg body weight streptozotocin cause a severe diabetic keto-acidosis. After 72 hours these animals and also a group of control animals receive 8.33 mCi/animal 3H-leucine intraperitoneally. By means of stripping film autoradiograms the rates of uptake of 3H-leucine in different areas of the rat brain are measured. The values of the control animals are compared with those of a fairly serious diabetes and those of a severe diabetic keto-acidosis. In the regions of the neocortex parietalis and of the thalamus the 3H-leucine values of the diabetic animals are considerably lower in comparison with the controls, and that irrespective of the degree of severity of the diabetic disease. Compared with the control animals the 3H-leucine values of diabetic animals decrease according to the degree of severity of the disease within the Ammon's horn and the dentate fascia. Within the Ammon's horn and dentate fascia also the zinc contents change very specifically in different areas with the degree of severity of diabetes mellitus. The zinc is identified on H2S-alcohol fixed brains by means of a photographic development. The particular significance of the Ammon's horn and the dentate fascia concerning diabetic metabolic conditions is discussed.

Animals

Insulin and glucagon secretion in diabetic and non-diabetic patients with circulating islet cell antibodies.

Thirty-nine patients (14 non-diabetics, 8 chemical diabetics, and 17 overt diabetics) with circulating islet cell antibodies (ICA) were studied. Insulin and glucagon secretion after oral (100 g) and intravenous glucose loading (200 mg/kg bolus injection followed by an infusion of 20 mg/min over 60 min) and arginine infusion (25 g over 30 minutes) were evaluated in these patients and in non diabetic and diabetic ICA-negative controls. In the non-diabetic groups with or without ICA, insulin and glucagon responses to glucose were similar. Moreover, in ICA positive patients the response of these hormones to arginine infusion was reduced. Similar alterations in insulin and glucagon secretion were observed in the CIA positive and negative patients with chemical or overt diabetes. In particular, fasting hyperglucagonaemia and glucagon hyperresponse to arginine are associated with a lack of insulin secretion in the patients with overt diabetes. Hormonal differences between diabetics with and without ICA could not be detected.

Adult