vitamin-b-12 and Diabetes-Mellitus--Type-1

Diabetic peripheral neuropathy (DPN) is a common and severe complication that affects 50% of people with diabetes. Painful DPN is reported to occur in 16% to 24% of people with diabetes. A complete and comprehensive management strategy for the prevention and treatment of DPN, whether painful or not, has not yet been defined.Research into treatment for DPN has been characterised by a series of failed clinical trials, with few noteworthy advances. Strategies that support peripheral nerve regeneration and restore neurological function in people with painful or painless DPN are needed. The amino acid acetyl-L-carnitine (ALC) plays a role in the transfer of long-chain fatty acids into mitochondria for β-oxidation. ALC supplementation also induces neuroprotective and neurotrophic effects in the peripheral nervous system. Therefore, ALC supplementation targets several mechanisms relevant to potential nerve repair and regeneration, and could have clinical therapeutic potential. There is a need for a systematic review of the evidence from clinical trials.. To assess the effects of ALC for the treatment of DPN.. On 2 July 2018, we searched the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, Embase, LILACS, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform. We checked references, searched citations, and contacted study authors to identify additional studies.. We included randomised controlled trials (RCTs) and quasi-RCTs of ALC compared with placebo, other therapy, or no intervention in the treatment of DPN. Participants could be of any sex and age, and have type 1 or type 2 diabetes mellitus, of any severity, with painful or painless DPN. We accepted any definition of minimum criteria for DPN, in accordance with the Toronto Consensus. We imposed no language restriction.Pain was the primary outcome, measured as the proportion of participants with at least 30% (moderate) or 50% (substantial) decrease in pain over baseline, or as the score on a visual analogue scale (VAS) or Likert scale for pain.. We followed standard Cochrane methods.. We included four studies with 907 participants, which were reported in three publications. Three trials studied ALC versus placebo (675 participants); in one trial the dose of ALC was 2000 mg/day, and in the other two trials, it was 1500 mg/day or 3000 mg/day. The fourth trial studied ALC 1500 mg/day versus methylcobalamin 1.5 mg/day (232 participants). The risk of bias was high in both trials of different ALC doses and low in the other two trials.No included trial measured the proportion of participants with at least moderate (30%) or substantial (50%) pain relief. ALC reduced pain more than placebo, measured on a 0- to 100-mm VAS (MD -9.16, 95% CI -16.76 to -1.57; three studies; 540 participants; P = 0.02; I² = 56%; random-effects; very low-certainty evidence; a higher score indicating more pain). At doses of 1500 mg/day or less, the VAS score after ALC treatment was little different from placebo (MD -0.05, 95% CI -10.00 to 9.89; two studies; 159 participants; P = 0.99; I² = 0%), but at doses greater than 1500 mg/day, ALC reduced pain more than placebo (MD -14.93, 95% CI -19.16 to -10.70; three studies; 381 participants; P < 0.00001; I² = 0%). This subgroup analysis should be viewed with caution as the evidence was even less certain than the overall analysis, which was already of very low certainty.Two placebo-controlled studies reported that vibration perception improved after 12 months. We graded this evidence as very low certainty, due to inconsistency and a high risk of bias, as the trial authors did not provide any numerical data. The placebo-controlled studies did not measure functional impairment and disability scores. No study used validated symptom scales. One study performed sensory testing, but the evidence was very uncertain.The fourth included study compared ALC with methylcobalamin, but did not report effects on pain. There was a reduction from baseline to 24 weeks in functional impairment and disability, based on the change in mean Neuropathy Disability Score (NDS; scale from zero to 10), but there was no important difference between the ALC group (mean score 1.66 ± 1.90) and the methylcobalamin group (mean score 1.35 ± 1.65) groups (P = 0.23; low-certainty evidence).One placebo-controlled study reported that six of 147 participants in the ALC > 1500 mg/day group (4.1%) and two of 147 participants in the placebo group (1.4%) discontinued treatment because of adverse events (headache, facial paraesthesia, and gastrointestinal disorders) (P. We are very uncertain whether ALC causes a reduction in pain after 6 to 12 months' treatment in people with DPN, when compared with placebo, as the evidence is sparse and of low certainty. Data on functional and sensory impairment and symptoms are lacking, or of very low certainty. The evidence on adverse events is too uncertain to make any judgements on safety.

Topics: Acetylcarnitine; Adult; Aged; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Female; Humans; Male; Middle Aged; Neuralgia; Pain Measurement; Placebos; Randomized Controlled Trials as Topic; Sensation; Vibration; Vitamin B 12

We herein report the case of a 66-year-old Japanese man with acute-onset type 1 diabetes mellitus (T1D) accompanied by pernicious anemia. After 2 weeks of polyuria, the patient developed insulin-deficient hyperglycemia with diabetic ketoacidosis in the absence of verifiable islet-related autoantibodies and began insulin therapy in 2001. Eight years later, he developed gastric autoantibody-positive pernicious anemia and began methylcobalamin treatment. Previous studies have reported cases of slowly progressive autoimmune T1D concomitant with pernicious anemia. The present case suggests that potential associations with organ-specific autoimmune disorders should be considered during the long-term follow-up of T1D patients, even though verifiable islet-related autoantibodies are undetectable.

Topics: Aged; Anemia, Pernicious; Asian People; Autoantibodies; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Humans; Hyperglycemia; Male; Stomach; Vitamin B 12

This study aimed to evaluate the effect of treatment with eye drops containing citicoline and vitamin B. In the results of follow-up evaluation, the DC and DP groups were significantly different: Significant reduction in function in terms of 10-2 FDT mean sensitivity and in morphology reflected by an increase in inner nuclear layer thickness and decrease in other plexiform layer thickness and foveal vessel density were observed in the DP group, while no such significant changes were observed in the DC group in the long term.. This pilot study indicated that patients with DM1 with mild signs of diabetic retinopathy (DR) who underwent treatment with citicoline and vitamin B. ClinicalTrials.gov identifier, NCT04009980.

Topics: Adult; Aged; Cytidine Diphosphate Choline; Diabetes Mellitus, Type 1; Diabetic Retinopathy; Female; Humans; Italy; Male; Middle Aged; Ophthalmic Solutions; Pilot Projects; Prospective Studies; Retina; Tomography, Optical Coherence; Visual Acuity; Vitamin B 12; Vitamins

To assess the efficacy and safety of acetyl-L-carnitine (ALC) on diabetic peripheral neuropathy compared with methylcobalamin (MC).. This was a multicenter, randomized, parallel-group, double-blind, double-dummy, positive-controlled, non-inferior phase II clinical trial. Diabetic patients with abnormal nerve conduction test results were randomized in a 1:1 ratio to receive oral ALC 500 mg t.i.d. or MC 0.5 mg t.i.d. for 24 weeks. The neuropathy symptom score, neuropathy disability score and neurophysiological parameters were measured during follow up.. A total of 232 patients were randomized (ALC n = 117, MC n = 115), 88% of which completed the trial. At week 24, patients from both groups had significant reductions in both neuropathy symptom score and neuropathy disability score with no significant difference between two groups (neuropathy symptom score reduction: ALC vs MC 2.35 ± 2.23, P < 0.0001 vs 2.11 ± 2.48, P < 0.0001, intergroup P = 0.38; neuropathy disability score reduction ALC vs MC 1.66 ± 1.90, P < 0.0001 vs 1.35 ± 1.65, P < 0.0001, intergroup P = 0.23). Neurophysiological parameters were also improved in both groups. No significant difference was found between groups in the development of adverse events.. ALC is as effective as MC in improving clinical symptoms and neurophysiological parameters for patients with diabetic peripheral neuropathy over a 24-week period with good tolerance.

Topics: Acetylcarnitine; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Double-Blind Method; Female; Humans; Male; Middle Aged; Neural Conduction; Severity of Illness Index; Treatment Outcome; Vitamin B 12

Autoimmune type 1 diabetic patients show a high prevalence of thyroid peroxidase (TPO), parietal cell (PCA), anti-adrenal (AAA) and anti-endomysium antibodies (EmA-IgA), which may be accompanied with clinical disease. We studied the grade of associated organ-specific autoimmunity and the pattern of prevalence of TPO and PCA by age, gender, duration, age at onset of diabetes, and HLA DR haplotype in 783 type 1 diabetic patients, consisting of 286 children and 497 adults (M/F: 389/394), with a mean diabetes duration of 11.8 +/- 10.1 years. The relationship between islet cell (ICA), glutamic acid decarboxylase-65 (GADA) and thyro-gastric auto-antibodies was also investigated. TPO were present in 21.6%, PCA in 18.3%, AAA in 2.2% and EmA-IgA in 2.1% of the patients. The presence of TPO is determined by gender (p < 0.0001), age (P = 0.0008), and PCA status (p = 0.029). The presence of PCA is only influenced by age (p = 0.0027) and TPO status (p = 0.0155). Patients with ICA+ > or = 3 years had a higher prevalence of thyro-gastric auto-antibodies (p = 0.045) than ICA- subjects. Also, PCA were more prevalent in GADA+ than GADA- patients (p = 0.005). We observed an association between HLA DR5 and PCA (p = 0.0012). Dysthyroidism was more prevalent in TPO+ than TPO- subjects (p < 0.0001). PCA+ subjects had a higher prevalence of iron deficiency anaemia (p = 0.0099) and pernicious anaemia (p < 0.0001) than PCA- patients. In conclusion, particularly type 1 diabetic patients with persisting ICA > or = 3 years or with GADA, show a high prevalence of thyro-gastric auto-antibodies. Based on antibody-positivity we observed a high prevalence of thyroid disease, iron deficiency anaemia and pernicious anaemia, which can compromise the health of the diabetic patient.

Topics: Adolescent; Adult; Age Factors; Anemia, Iron-Deficiency; Anemia, Pernicious; Autoantibodies; Autoimmunity; Child; Child, Preschool; Diabetes Mellitus, Type 1; Female; Glutamate Decarboxylase; Glycated Hemoglobin; Humans; Iodide Peroxidase; Iron; Islets of Langerhans; Magnesium; Male; Organ Specificity; Parietal Cells, Gastric; Prevalence; Sex Factors; Thyroid Diseases; Vitamin B 12

We studied the clinical and neurophysiological effects of methylcobalamin on patients with diabetic neuropathy. In a double-blind study, the active group showed statistical improvement in the somatic and autonomic symptoms with regression of signs of diabetic neuropathy. Motor and sensory nerve conduction studies showed no statistical improvement after 4 months. The drug was easily tolerated by the patients and no side effects were encountered.

Topics: Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Female; Humans; Male; Middle Aged; Muscle Contraction; Neurologic Examination; Peripheral Nerves; Reaction Time; Reflex, Stretch; Sensation; Synaptic Transmission; Vitamin B 12

Type 1 diabetes mellitus (T1DM) is a lifelong diagnosis that involves immune-mediated damage of pancreatic beta cells and subsequent hyperglycemia, manifesting as: polyuria, polydipsia, polyphagia, and weight loss. Treatment of type 1 diabetes centers on insulin administration to replace or supplement the body's own insulin with the goal of achieving euglycemia and preventing or minimizing complications. Patients with T1DM are at risk for developing other autoimmune conditions, most commonly thyroid or celiac disease.. A 20-year-old African American female with T1DM was referred by her endocrinologist to pediatric gastroenterology for 2 months of nocturnal, non-bloody diarrhea, left lower quadrant pain, and nausea; she was also being followed by neurology for complaints of lower extremity paresthesias and pain. The patient's initial lab-workup was remarkable for a low total Immunoglobulin A (IgA) level of < 6.7 mg/dL. As IgA deficiency is associated with an increased risk of celiac disease, the patient underwent upper and lower endoscopy, which was grossly unremarkable; however, histology revealed a pattern consistent with autoimmune gastritis. Subsequent serum evaluation was remarkable for an elevated fasting gastrin level and an elevated parietal cell antibody level without macrocytic anemia, iron deficiency, or vitamin B12 depletion. The patient was diagnosed with autoimmune gastritis (AIG) and subsequently initiated on parenteral B12 supplementation therapy with improvement in her neurologic and gastrointestinal symptoms.. This case illustrates the importance of recognition of red flag findings in a patient with known autoimmune disease. Following well-established health maintenance recommendations for individuals with T1DM ensures that common comorbidities will be detected. Autoimmune gastritis, while a rarer pathology in the pediatric population, deserves consideration in patients with pre-existing autoimmune conditions and new gastrointestinal or neurologic symptoms, as AIG can be associated with poor outcomes and risk of malignancy. Initial lab findings associated with an eventual diagnosis of AIG typically include anemia, iron deficiency, or Vitamin B12 deficiency. However, as demonstrated in this case, symptoms of AIG can rarely present before anemia or Vitamin B12 deficiency develops. To prevent permanent neurological damage, parenteral Vitamin B12 therapy must be considered even in the absence of Vitamin B12 deficiency, especially in those patients already experiencing neurological symptoms.

Topics: Adult; Anemia, Iron-Deficiency; Autoimmune Diseases; Celiac Disease; Child; Diabetes Mellitus, Type 1; Diarrhea; Female; Gastritis; Humans; Insulins; Pain; Vitamin B 12; Vitamin B 12 Deficiency; Young Adult

Celiac disease (CD) accompanying autoimmune endocrine diseases (AED) is generally asymptomatic. This study aimed to evaluate the frequency of clinically overt or silent CD in patients diagnosed with autoimmune endocrinopathy and the clinical effects of silent CD in these endocrinopathies. The study included 166 patients with known or newly diagnosed mono-/polyglandular AED and 90 age- and gender-matched healthy controls. The patients were classified into four groups: type 1 diabetes mellitus (DM) (n=44), Hashimoto's thyroiditis (HT) (n=68), Addison's disease (AD) (n=17), and autoimmune polyglandular syndrome (APS) (n=37). All subjects were serologically screened for tissue transglutaminase antibody (tTG) IgA and IgG. In addition, to evaluate the possible systemic consequences of CD, serum parathormone (PTH), 25-hydroxicholecalsiferol (25-OH-Vit D), vitamin B12, folic acid, iron, iron-binding capacity (IBC), and ferritin levels were measured. In the total series, 193 (75.4%) individuals were females, and 63 (24.6%) were males. TTG IgA antibody positivity was found in 23 among 166 patients, while no positivity was encountered in the healthy control group. The highest rates of positive tTg IgA frequency were detected in AD, with 29.4% (5/17). Serum 25-OH-Vit D, vitamin B12, folic acid, iron, and ferritin levels were significantly lower in AEDs compared to controls (p<0.001), and the lowest these parameters were detected in patients with AD. The serologic CD prevalence is higher in autoimmune mono-/and polyglandular endocrine diseases than in the control group. The data support recommends regular screening for CD in all patients with AEDs.

Topics: Addison Disease; Autoantibodies; Celiac Disease; Diabetes Mellitus, Type 1; Female; Ferritins; Folic Acid; Gastrointestinal Absorption; Humans; Immunoglobulin A; Iron; Male; Vitamin B 12

More and more studies have shown that the intestinal microbiota is the main factor in the pathogenesis of type 1 diabetes mellitus (T1DM). Beta cell expansion factor A (BefA) is a protein expressed by intestinal microorganisms. It has been proven to promote the proliferation of β-cells and has broad application prospects. However, as an intestinal protein, there have not been studies and reports on its application in diabetes and its mechanism of action. In this study, a T1DM model induced by multiple low-dose STZ (MLD-STZ) injections was established, and BefA protein was administered to explore its therapeutic effect in T1DM and the potential mechanism of intestinal microbiota. BefA protein significantly reduced the blood glucose, maintained the body weight, and improved the glucose tolerance of the mice. At the same time, the BefA protein significantly increased the expression of ZO-1, Occludin, and significantly reduced the expression of TLR-4, Myd88, and p-p65/p65. BefA protein significantly reduced the relative expression of pro-inflammatory cytokines IL-1β, IL-6 and TNF-α. In addition, our high-throughput sequencing shows for the first time that the good hypoglycemic effect of BefA protein is strongly related to the increase in the abundance of the beneficial gut bacteria

Topics: Animals; Cell Proliferation; Diabetes Mellitus, Type 1; Gastrointestinal Microbiome; Mice; Vitamin B 12

Topics: Adaptor Proteins, Signal Transducing; Animals; Cardiomyopathies; Diabetes Mellitus, Type 1; DNA-Cytosine Methylases; Female; Insulin-Like Growth Factor I; Male; Mice; Mice, Inbred C57BL; Oxidative Stress; Signal Transduction; Suppressor of Cytokine Signaling 1 Protein; Suppressor of Cytokine Signaling 3 Protein; Vitamin B 12

Vitamin B12 and folate deficiency are not only linked to hematological, neurological, and cardiovascular diseases, but are also associated with insulin resistance. Metformin can decrease vitamin B12 and folate concentrations.. To examine (1) effects of short-term metformin treatment on serum holotranscobalamin (holoTC) and folate and (2) their association with insulin sensitivity in recent-onset type 2 diabetes.. This cross-sectional analysis comprised patients (known disease duration <12 months) on metformin monotherapy (MET, n = 123, 81 males, 53 ± 12 years) or nonpharmacological treatment (NPT, n = 126, 77 males, 54 ± 11 years) of the German Diabetes Study.. HoloTC (enzyme-linked immunosorbent assay), cobalamin, and folate (electrochemiluminescence); beta-cell function and whole-body insulin sensitivity, measured during fasting (HOMA-B, HOMA-IR) and intravenous glucose tolerance tests combined with hyperinsulinemic-euglycemic clamp tests.. HoloTC (105.4 [82.4, 128.3] vs 97 [79.7, 121.9] pmol/L) and folate concentrations (13.4 [9.3, 19.3] vs 12.7 [9.3, 22.0] nmol/L) were similar in both groups. Overall, holoTC was not associated with fasting or glucose-stimulated beta-cell function and insulin-stimulated glucose disposal. Cobalamin measurements yielded similar results in representative subgroups. In NPT but not MET, folate levels were inversely correlated with HOMA-IR (r = -0.239, P = .007). Folate levels did not relate to insulin sensitivity or insulin secretion in the whole cohort and in each group separately after adjustment for age, body mass index, and sex.. Metformin does not affect circulating holoTC and folate concentrations in recent-onset type 2 diabetes, rendering monitoring of vitamin B12 and folate dispensable, at least during the first 6 months after diagnosis or initiation of metformin.

Topics: Adolescent; Adult; Aged; Biomarkers; Blood Glucose; Cross-Sectional Studies; Diabetes Mellitus, Type 1; Female; Folic Acid; Folic Acid Deficiency; Follow-Up Studies; Humans; Hypoglycemic Agents; Insulin Resistance; Male; Metformin; Middle Aged; Prognosis; Prospective Studies; Vitamin B 12; Vitamin B 12 Deficiency; Young Adult

Topics: Diabetes Mellitus, Type 1; Diarrhea; Humans; Male; Metformin; Middle Aged; Vitamin B 12; Vitamin B 12 Deficiency

We aimed to assess the prevalence of autoantibodies against the 4A subunit of the gastric proton pump (ATP4A) in pediatric type 1 diabetes (T1D) patients and explore the relationship between ATP4A positivity and blood cell count, iron turnover, and vitamin B12 concentration.. The study included 94 (59% female) T1D children (aged 12.5 ± 4.1 years, T1D duration 4.2 ± 3.6 years, HbA1c 7.3 ± 1.5% (57 ± 12.6 mmol/mol) with no other autoimmune diseases.. ATP4A antibodies were measured in T1D patients using a radioimmunoprecipitation assay. Blood cell count, iron concentration, total iron binding capacity, ferritin, transferrin, hepcidin, and vitamin B12 concentration were measured in all the study participants.. A total of 16 (17%) children were ATP4A positive. Serum concentrations of ferritin were significantly lower in ATP4A positive than in antibody negative subjects (P = .034). Overall the levels of ATP4A antibodies (ATP4A Index) correlated positively with the age at T1D diagnosis (r = 0.228, P = .026) and negatively with ferritin levels (r = -0.215, P = .037). In ATP4A positive patients, the ATP4A Index correlated positively with age at diagnosis (r = 0.544, P = .032) and negatively with vitamin B12 levels (r = -0.685, P = .004).. ATP4A antibodies were present in a significant proportion of children with T1D. Higher ATP4A levels in T1D children are associated with lower, yet still fitting within the normal range, levels of vitamin B12, and ferritin. Routine screening of T1D children for gastric autoimmunity (ATP4A) should be considered with follow-up of those positive for vitamin B12 and iron deficiency.

Topics: Adolescent; Autoantibodies; Blood Cell Count; Child; Child, Preschool; Cohort Studies; Diabetes Mellitus, Type 1; Female; H(+)-K(+)-Exchanging ATPase; Humans; Iron; Male; Vitamin B 12; Young Adult

Little is known about arsenic and diabetes in youth. We examined the association of arsenic with type 1 and type 2 diabetes in the SEARCH for Diabetes in Youth Case-Control (SEARCH-CC) study. Because one-carbon metabolism can influence arsenic metabolism, we also evaluated the potential interaction of folate and vitamin B12 with arsenic metabolism on the odds of diabetes.. Six hundred eighty-eight participants <22 years of age (429 with type 1 diabetes, 85 with type 2 diabetes, and 174 control participants) were evaluated. Arsenic species (inorganic arsenic [iAs], monomethylated arsenic [MMA], dimethylated arsenic [DMA]), and one-carbon metabolism biomarkers (folate and vitamin B12) were measured in plasma. We used the sum of iAs, MMA, and DMA (∑As) and the individual species as biomarkers of arsenic concentrations and the relative proportions of the species over their sum (iAs%, MMA%, DMA%) as biomarkers of arsenic metabolism.. Median ∑As, iAs%, MMA%, and DMA% were 83.1 ng/L, 63.4%, 10.3%, and 25.2%, respectively. ∑As was not associated with either type of diabetes. The fully adjusted odds ratios (95% CI), rescaled to compare a difference in levels corresponding to the interquartile range of iAs%, MMA%, and DMA%, were 0.68 (0.50-0.91), 1.33 (1.02-1.74), and 1.28 (1.01-1.63), respectively, for type 1 diabetes and 0.82 (0.48-1.39), 1.09 (0.65-1.82), and 1.17 (0.77-1.77), respectively, for type 2 diabetes. In interaction analysis, the odds ratio of type 1 diabetes by MMA% was 1.80 (1.25-2.58) and 0.98 (0.70-1.38) for participants with plasma folate levels above and below the median (P for interaction = 0.02), respectively.. Low iAs% versus high MMA% and DMA% was associated with a higher odds of type 1 diabetes, with a potential interaction by folate levels. These data support further research on the role of arsenic metabolism in type 1 diabetes, including the interplay with one-carbon metabolism biomarkers.

Topics: Adolescent; Arsenic; Biomarkers; Case-Control Studies; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Environmental Exposure; Female; Folic Acid; Humans; Male; Vitamin B 12; Young Adult

To assess plasma concentrations of folic acid, vitamin B12, and total plasma homocysteine (tHCY) during fasting and after methionine load in young patients with Type 1 diabetes mellitus (T1DM).. We enrolled 41 young patients with T1DM without any sign of microvascular complications and 123 healthy controls in a 1:3 case-control study. Fasting and post-methionine load (PML) tHCY, folic acid, and vitamin B12 levels were measured in both groups. Data regarding chronological age, metabolic control (assessed by mean values of glycated hemoglobin in the last 12 months) and disease duration were also recorded.. Fasting and PML tHCY levels were significantly lower in patients than in controls: 7.3+/-2.7 micromol/l vs 8.3+/-2.5 micromol/l (p=0.01), and 16.7+/-5.8 micromol/l vs 17.3+/-4.3 micromol/l (p=0.01), respectively. No correlation was found between fasting and PML tHCY levels and chronological age, disease duration, metabolic control, and insulin requirement. Patients had significantly higher vitamin B12 levels compared to controls: 767+/-318 pg/ml vs 628+/-236 pg/ml (p=0.003), while folic acid turned out to be lower in patients than in controls: 5.3+/-1.9 nmol/l vs 7.5+/-2.6 nmol/l (p<0.0001).. Adolescents and young adults with T1DM without microvascular complications showed lower tHCY both during fasting and after methionine load. Lower folate concentrations in these patients might benefit from food fortification.

Topics: Adolescent; Adult; Aging; Blood Glucose; Case-Control Studies; Child; Diabetes Mellitus, Type 1; Fasting; Female; Folic Acid; Homocysteine; Humans; Male; Methionine; Sex Characteristics; Vitamin B 12; Young Adult

The most frequent organ-specific autoimmune diseases associated with type 1 diabetes mellitus in children are hypothyroidism and celiac disease. Among adults, other associations exist, notably with pernicious anemia, which is extremely rare in children. We relate the observation of an adolescent with type 1 diabetes mellitus and hypothyroidism, admitted for severe anemia in addition to chronic anemia caused by autoimmune gastritis. Blood cell count showed severe aregenerative anemia with pancytopenia, with signs of non-autoimmune hemolysis. Vitamin B12 levels were low, bone marrow aspiration revealed erythroid hyperplasia, and anti-intrinsic factor antibodies were positive, providing the diagnosis of pernicious anemia. Treatment with intramuscular vitamin B12 produced brisk reticulosis after 6 days, with a subsequent rapid resolution of the anemia. Follow-up of type 1 diabetes mellitus in children requires screening for organ-specific autoimmune diseases; in case of unexplained anemia, autoimmune gastritis must be suggested. It can evolve into pernicious anemia.

Topics: Adolescent; Anemia, Pernicious; Autoimmune Diseases; Diabetes Mellitus, Type 1; Female; Gastritis; Hemolysis; Humans; Pancytopenia; Vitamin B 12; Vitamins

A 14 year male adolescent born of 2nd degree consanguineous marriage presented with asymptomatic proteinuria and severe anemia. He had leucopenia, anisopoikilocytosis, megaloblastic erythropoiesis, megakaryocytes with low serum B12 level. His younger sibling was similarly affected. This combination suggested Imerslund-Grasbeck syndrome. The hemoglobin levels improved with injection of vitamin B12 but proteinuria persisted. During follow-up, he developed ketoacidosis due to insulin dependent diabetes mellitus. This rare combination has not been reported in the Indian literature.

Topics: Adolescent; Anemia, Megaloblastic; Child; Diabetes Mellitus, Type 1; Failure to Thrive; Humans; Hyperpigmentation; Intestinal Absorption; Malabsorption Syndromes; Male; Mutation, Missense; Prevalence; Risk Factors; Syndrome; Vitamin B 12; Vitamin B 12 Deficiency

The potential utility of vitamin B12 carrier system for the oral delivery of conjugated peptides/proteins and enhancement of nanoparticles (NPs) transport has been demonstrated. The present study aims to optimize the effectiveness of VB12-NPs conjugates using different levels of cross-linking, linked with different VB(12)-coatings and evaluates in animal models to investigate an efficient insulin carrier. Amino alkyl VB12 derivatives suitable for oral delivery were synthesized at 5'hydoxy ribose and e-propionamide sites via carbamate and ester/amide linkages, and were coupled to succinic acid modified dextran NPs of varied cross-linking. VB12 binding was confirmed by XPS analysis, and was quantified by HPLC (4.0 to 5.7% w/w of NPs). These polydisperse NPs conjugates showed higher size, high insulin entrapment and faster insulin release with low levels of cross-linking. These VB12-NPs conjugates (150-300 nm) showed profound (70-75% blood glucose reductions) and prolonged (54 h) anti-diabetic effects with biphasic behaviour in STZ diabetic rats. NPs with the low levels of cross-linking were found to be superior carriers, and were more effective with VB12 derivatives of carbamate linkage. The pharmacological availability relative to SC insulin was found to be 29.4%, which was superior compared to NPs conjugate of ester linked VB12 (1.5 fold) and relatively higher cross-linked particles (1.1 fold). Further, the NPs carrier demonstrated a similar oral insulin efficacy in congenital diabetic mice (60% reduction at 20 h). Significant quantities of plasma insulin were found in both animal models (231 and 197 muIU/ml). At two investigated doses, the carrier system shows dose response. Pre-dosing with a large excess of free VB12 minimized the observed activity, indicating predominance of VB12 mediated uptake. It is concluded that VB12-dextran NPs conjugate is a viable carrier for peroral insulin delivery to treat diabetics.

Topics: Administration, Oral; Animals; Blood Glucose; Chemistry, Pharmaceutical; Cross-Linking Reagents; Dextrans; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Dose-Response Relationship, Drug; Drug Carriers; Drug Compounding; Epichlorohydrin; Female; Hypoglycemic Agents; Insulin; Mice; Mice, Inbred NOD; Nanoparticles; Particle Size; Rats; Rats, Wistar; Solubility; Species Specificity; Vitamin B 12

Topics: Administration, Oral; Controlled Clinical Trials as Topic; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Drug Therapy, Combination; Humans; Placebos; Prodrugs; Pyridoxine; Thiamine; Time Factors; Vitamin B 12; Vitamin B 6

Subclinical inflammation has been implicated in the initiation and/or progression of atherosclerosis. Diabetes mellitus and obesity are risk factors for atherosclerosis, and asymptomatic low grade inflammation occurs prior to overt vascular lesions in these patients. In contrast to adults, little information exists concerning low grade inflammation in young type 1 diabetes and juvenile obesity.. To investigate low grade inflammation and immune activation in juvenile diabetes mellitus and obesity.. hs-CRP, soluble interleukin-2 receptor (sIL-2R), C-peptide, insulin, cortisol, vitamin B12, folic acid, leptin, and homocysteine were determined in 148 patients with juvenile type 1 diabetes, 86 obese children and 142 normal weighted age-matched healthy controls. Intima-media thickness (IMT) and lumen diameter of both common carotid arteries (CCA) was measured by ultrasonography in 52 healthy pediatric controls, 10 diabetics, and 34 obese juveniles.. Serum hs-CRP was significantly elevated in patients with type 1 diabetes (p < 0.0001), and obese children (p < 0.0001) as compared to the control group. The obese juveniles (p < 0.0001) and the diabetics (p < 0.0001) showed significantly increased values for IMT of CAAs. Levels of homocysteine, sIL-2R, insulin, cortisol, vitamin B12, and folic acid did not differ from the controls. The elevation of hs-CRP was more pronounced in obesity as compared to type 1 diabetes (p < 0.0001), and the hs-CRP values correlated significantly with body mass index standard deviation score (BMI-SDS) values. Furthermore, the IMT and the luminal diameter of CCAs showed significant correlations with BMI-SDS values.. A low grade inflammation as determined by serum hs-CRP is significantly increased in children with type 1 diabetes, and even more pronounced in apparently healthy juveniles with obesity. The increased IMT of CCAs strongly argues for an association between this low grade inflammation and early atherosclerotic vessel injury.

Topics: Adolescent; Arteriosclerosis; Body Mass Index; C-Peptide; C-Reactive Protein; Carotid Artery, Common; Child; Diabetes Mellitus, Type 1; Female; Folic Acid; Homocysteine; Humans; Inflammation; Leptin; Male; Obesity; Receptors, Interleukin-2; Tunica Intima; Vitamin B 12

Topics: Adolescent; Anemia, Pernicious; Diabetes Mellitus, Type 1; Female; Gastritis, Atrophic; Gastroparesis; Humans; Thyrotoxicosis; Vitamin B 12

The objective was to investigate total plasma homocyst(e)ine (tHcy), methylenetetrahydrofolate reductase (MTHFR) genotype, and the contribution of diet to homocysteine values in children and adolescents with type 1 diabetes and a control group.. A total of 78 children with type 1 diabetes and 59 members of an age- and sex-matched control group were recruited. Fasting samples were collected for tHcy, MTHFR genotype, serum vitamin B(12), serum folate, red cell folate, and plasma creatinine. Food frequency questionnaires targeted intake of folate, vitamin B(6), and vitamin B(12).. Fasting tHcy was reduced in patients compared with the control group (4.7 vs 5.9 micromol/L, P <.001). Serum folate (P =.002), red cell folate(P <.001), and serum vitamin B(12) (P =.005) were higher, and plasma creatinine was lower. A significant difference in tHcy values between patients and the control group persisted after correction was done for these factors (r = 0.1, P =.02). No difference was seen in the frequency of MTHFR polymorphisms. tHcy was not elevated in those patients with the 677TT or 677T/1298C genotypes, although red cell folate was significantly higher in members of the case (P =.01) and control groups (P =.05) with a 677 TT genotype. Dietary intake of folate correlated with serum folate (r = 0.4,P =.005).. tHcy values are lower in children and adolescents with type 1 diabetes. Higher serum levels of folic acid and vitamin B(12), reflecting differences in dietary intake between children with diabetes and members of a control group, partially account for this difference.

Topics: Adolescent; Child; Creatinine; Diabetes Mellitus, Type 1; Erythrocytes; Female; Folic Acid; Genotype; Homocysteine; Homocystine; Humans; Male; Methylenetetrahydrofolate Reductase (NADPH2); Oxidoreductases Acting on CH-NH Group Donors; Vitamin B 12

Topics: Biomarkers; Blood Pressure; Creatinine; Diabetes Mellitus, Type 1; Diabetic Retinopathy; Female; Folic Acid; Gene Frequency; Homocysteine; Homozygote; Humans; Male; Methylenetetrahydrofolate Reductase (NADPH2); Oxidoreductases Acting on CH-NH Group Donors; Point Mutation; Vitamin B 12

To determine the prevalence of pernicious anaemia in patients with Type 1 diabetes mellitus and autoimmune thyroid disease.. A randomly selected asymptomatic group of 63 patients with Type 1 diabetes who also had autoimmune thyroid disease was studied. Blood samples were taken and assayed for serum B12. Those subjects with serum B12 concentrations below the reference range had a further blood sample taken for determination of intrinsic factor antibody.. One patient had been diagnosed previously to have pernicious anaemia. Three patients had low serum B12 concentration and positive intrinsic factor antibody, confirming the diagnosis of pernicious anaemia. The prevalence of pernicious anaemia in this population with Type 1 diabetes and concomitant autoimmune thyroid disease was 6.3%. In female patients the prevalence of pernicious anaemia was 8.5%.. Patients who have both Type 1 diabetes mellitus and autoimmune thyroid disease are at risk of developing pernicious anaemia.

Topics: Aged; Aged, 80 and over; Anemia, Pernicious; Autoantibodies; Diabetes Mellitus, Type 1; Female; Folic Acid; Graves Disease; Humans; Hypothyroidism; Intrinsic Factor; Middle Aged; Prevalence; Vitamin B 12

Homocysteine is involved in a complex and dynamic system of vascular injury and repair and may thus contribute to the development of diabetic microangiopathy. This still debated issue has important scientific and clinical implications, since hyperhomocysteinemia can be corrected nutritionally.. 1) To evaluate the association between fasting plasma homocysteine, type 1 diabetes and its microvascular complications; 2) to elucidate the basis of this association by investigating the major determinants of plasma homocysteine in relation to diabetic microangiopathy.. We studied sixty-six consecutive patients with type 1 diabetes mellitus of > 10 years duration and normal serum creatinine (< 115 mumol/L, 1.3 mg/dL), and free from clinically detectable cardiovascular diseases. Forty-four non-diabetic controls were also studied. Plasma concentrations of homocysteine, folate and vitamin B12 were investigated together with the C677T mutation in the gene coding for methylenetetrahydrofolate reductase (MTHFR), a key enzyme in homocysteine metabolism. Renal and retinal diabetic complications were evaluated as albumin/creatinine ratio on early-morning, urine spot collection and fundus photographs.. Fasting plasma homocysteine levels were very similar in patients and controls. Patients with microalbuminuria or proliferative retinopathy had significantly higher values than those without: 9.4 +/- 3.1 vs 7.4 +/- 2.8 mumol/L, p < 0.02 and 9.5 +/- 2.6 vs 7.3 +/- 3.0 mumol/L, p < 0.05. This difference was not attributable to confounders, such as age, sex and smoking, nor to dissimilar plasma folate and vitamin B12 concentrations. In contrast, homozygosity for the C677T mutation in the MTHFR gene--the commonest genetic defect linked to moderately increased plasma homocysteine--was significantly more frequent in patients with microalbuminuria and/or proliferative retinopathy (50% vs 13%, p < 0.004), odds ratio 6.7 (95% CI 1.7-27.6).. Type 1 diabetes as such is not associated with increased plasma homocysteine levels, though patients with microalbuminuria and/or proliferative retinopathy display significantly higher values than those without. This difference is not attributable to obvious confounders, nor to differences in vitamin status, and may be partly mediated by genetic factors. Plasma homocysteine, together with other diabetes-related noxae, may thus be in a position to contribute to the development of nephropathy and the progression of retinopathy.

Topics: Adult; Albuminuria; Case-Control Studies; Creatinine; Diabetes Mellitus, Type 1; Diabetic Angiopathies; Diabetic Nephropathies; Diabetic Retinopathy; Female; Folic Acid; Homocysteine; Humans; Male; Methylenetetrahydrofolate Reductase (NADPH2); Oxidoreductases Acting on CH-NH Group Donors; Point Mutation; Vitamin B 12

The plasma concentrations of total homocysteine (tHcy) and total cysteine (tCys) are determined by intracellular metabolism and by renal plasma clearance, and we hypothesized that glomerular filtration is a major determinant of plasma tHcy and tCys. We studied the relationships between the glomerular filtration rate (GFR) and plasma tHcy and tCys in populations of diabetic patients with particularly wide ranges of GFR.. We measured GFR, urine albumin excretion rate (UAER), plasma tHcy, tCys, methionine, vitamin B12, folate, C-peptide, and routine parameters in 50 insulin-dependent diabetes mellitus (IDDM) and 30 non-insulin-dependent diabetes mellitus (NIDDM) patients. All patients underwent intensive insulin treatment and had a serum creatinine concentration below 115 micromol/liter.. Mean plasma tHcy in diabetic patients (0.1 micromol/liter) was lower than in normal persons (11.1 micromol/liter, P = 0.0014). Mean plasma tCys in diabetic patients (266.1 micromol/liter) was also lower than in normal persons (281.9 micromol/liter, P = 0.0005). Seventy-three percent of the diabetic patients had relative hyperfiltration. Plasma tHcy and tCys were closely and independently associated with GFR, serum folate, and serum B12. However, plasma tHcy was not independently associated with any of the 22 other variables tested, including age, serum creatinine concentration, UAER, total daily insulin dose, and glycemic control.. Glomerular filtration rate is an independent determinant of plasma tHcy and tCys concentrations, and GFR is rate limiting for renal clearance of both homocysteine and cysteine in diabetic patients without overt nephropathy. Declining GFR explains the age-related increase in plasma tHcy, and hyperfiltration explains the lower than normal mean plasma tHcy and tCys concentrations in populations of diabetic patients.

Topics: Adult; Aged; Aged, 80 and over; Aging; Creatinine; Cysteine; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Folic Acid; Glomerular Filtration Rate; Homocysteine; Humans; Insulin; Middle Aged; Vitamin B 12

In a previous study, we showed that diabetic patients exhibited significantly increased concentrations of total plasma homocysteine (tHcy), but not until the onset of nephropathy. It was suggested that the hyperhomocysteinaemia might contribute to the accelerated atherosclerotic process in diabetic patients. In the present study, we have analysed the main determinants of plasma homocysteine (i.e. serum cobalamin, blood folate and serum creatinine), and also some other parameters related to diabetes mellitus, such as medical history, metabolic and renal quantities, on two occasions with a 5-year interval in 50 patients with insulin-dependent diabetes mellitus, in order to further elucidate the relation between plasma tHcy and diabetes mellitus. The result of the present study shows that diabetic patients with the lowest age at onset and with the poorest metabolic control are those most prone to a rapid increase in plasma tHcy concentration. The increment in plasma tHcy concentration in this group of patients may at least partly be explained by a marginal deficiency of blood folate concentrations.

Topics: Adult; Age of Onset; Diabetes Mellitus, Type 1; Diabetic Retinopathy; Female; Folic Acid Deficiency; Follow-Up Studies; Homocysteine; Humans; Male; Middle Aged; Vitamin B 12

Islets of Langerhans surrounded by a semipermeable membrane to prevent the host immunosystem is a potential way to treat type I diabetes mellitus. In this study, a series of poly (vinyl alcohol) membranes were formed by adding polyethylene glycols to create pores in the skin layer. The permeability study showed the skin layer structure had an influence on the diffusion of low molecular weight glucose, vitamin B12 and insulin. The mass transfer coefficient was improved from 1.04 x 10(-4) to 2.16 x 10(-4) cm/ sec for glucose, from 2.84 x 10(-5) to 8.36 x 10(-5) cm/sec for vitamin B12 and from 1.45 x 10(-6) to 4.15 x 10(-6) cm/sec for insulin, whereas the passage of immunoglobulin G was completely prevented, indicating that these membranes could be effective in protecting islets from immunorejection. Thus such a membrane is an alternative potential material for artificial islets. In addition, we examined the insulin secretory response of islets separated by a poly(vinyl alcohol) membrane. We found that the insulin-secretion rate is relatively rapid compared to the permeation rate of insulin; thus, the process of the artificial islets is insulin-diffusion-controlled.

Topics: Biocompatible Materials; Diabetes Mellitus, Type 1; Diffusion; Glucose; Humans; Immunoglobulin G; Insulin; Kinetics; Membranes, Artificial; Microscopy, Electron, Scanning; Pancreas, Artificial; Permeability; Polyvinyl Alcohol; Vitamin B 12

The reactive vascular-injuring amino acid homocysteine was previously shown to be increased in plasma in diabetic patients with clinical signs of nephropathy. In this study, plasma homocysteine was measured in type 1 diabetic patients with normoalbuminuria (n = 22), microalbuminuria (n = 40) and proteinuria (n = 14) in order to investigate whether plasma homocysteine levels are increased already at the stage of incipient nephropathy, i.e. microalbuminuria. Furthermore, patients were characterized according to the degree of retinopathy. Plasma homocysteine in the whole population (n = 76) was related to B-Folate (r = 0.38, p < 0.01), S-Creatinine (r = 0.55, p < 0.001), S-Urea (r = 0.37, p < 0.01), U-Albumin (r = 0.46, p < 0.001), urinary N-acetyl-beta- glucosaminidase (r = 0.40, p < 0.001), systolic blood pressure (r = 0.36, p < 0.01) and diabetes duration (r = 0.44, p < 0.001). There were no differences in plasma homocysteine levels between patients with normoalbuminuria (8.0 +/- 1.7 mumol l-1; mean +/- SD) and those with microalbuminuria (9.1 +/- 3.4 mumol l-1). However, patients with clinical signs of nephropathy had higher plasma homocysteine levels (12.9 +/- 5.7 mumol l-1, p < 0.01) compared to the other two groups. There was no association between plasma homocysteine levels and different degrees of retinopathy. Thus, the present study does not show any relation between plasma homocysteine levels and early stages of diabetic nephropathy or retinopathy indicating that elevated concentrations of plasma homocysteine does not explain the increased risk for atherosclerosis observed in patients with microalbuminuria.

Topics: Adult; Albuminuria; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Diabetic Retinopathy; Female; Homocysteine; Humans; Male; Middle Aged; Vitamin B 12

To determine the prevalence of latent pernicious anaemia (PA) in Type 1 diabetics.. Patients with Type 1 diabetes were screened at two yearly intervals on a continuing basis.. Diabetic Unit, Royal Perth Hospital, Western Australia.. Three hundred and seventy-one patients, 156 females and 215 males, attending a diabetic clinic. They were classified as having Type 1 diabetes on the basis of age of onset less than 40 years and requiring insulin from the start.. Serum cobalamin levels were measured and studies of thyroid function and a blood count were done. Patients with a reduced serum level of cobalamin had tests for cobalamin absorption.. Six patients had a low serum cobalamin level; five showed malabsorption of the vitamin which could be corrected by the addition of intrinsic factor. Four of these patients had no clinical signs of PA. The fifth was mildly anaemic (haemoglobin level 111 g/L) and had megaloblastic bone marrow. He was classified as having frank PA. The sixth patient was not available for further testing. These results give a prevalence of latent PA of 11 per 1000 in Type 1 diabetics, compared with 3.9 per 1000 in diabetics with clinically manifest disease and 1.27 per 1000 in the general population. All four patients with latent PA had hypothyroidism, based on low thyroxine levels, increased levels of thyroid stimulating hormone and the presence of thyroid antibodies.. Latent PA is not uncommon in Type 1 diabetics. It has a long preclinical course and occurs in those patients with thyroid disease. The screening of Type 1 diabetics for latent PA has worthwhile benefits as a "preventive" health measure.

Topics: Anemia, Pernicious; Diabetes Mellitus, Type 1; Female; Follow-Up Studies; Humans; Hypothyroidism; Male; Mass Screening; Thyroid Function Tests; Vitamin B 12

The frequency and significance of gastric parietal cell autoimmunity was assessed in 771 patients with insulin-dependent diabetes (IDD) of onset before 30 yr of age. Gastric parietal autoantibodies (PCA) were found 4 times more frequently in the patients with IDD (9%) than among 600 matched nondiabetic controls (2%). Caucasian female patients with IDD had PCA twice as frequently as male patients. Thyroid microsomal autoantibodies were more frequent in patients with IDD and PCA, than in those with IDD alone (Caucasian 46% versus 18%, black 25% versus 2.5%). A history of pernicious anemia and/or PCA was found in 25 or 40 families of IDD probands with PCA. Achlorhydria was demonstrated in 6 of 11 patients (54%) with PCA but in none of seven IDD patients without PCA. The six patients with achlorhydria had significantly lower uptakes of oral radiolabeled cobalamin, lower serum cobalamin levels, lower intrinsic factor-R protein ratios in their gastric aspirates, and lower plasma ferritin levels than patients with IDD but without PCA. None of the study group had IF antibodies in their serum or gastric juice. Overt pernicious anemia and neuropathy were found in one patient with PCA. Young patients with IDD at risk for atrophic gastritis and cobalamin deficiency can initially be identified by screening for PCA. Many of these young patients with PCA already have achlorhydria and evidence of decreased absorption of cobalamin. These patients can then be followed with cobalamin levels and/or with complete blood counts to identify those requiring therapy.

Topics: Achlorhydria; Adolescent; Adult; Anemia, Hypochromic; Autoantibodies; Child; Diabetes Mellitus, Type 1; Female; Ferritins; Humans; Male; Stomach; Vitamin B 12

Circulating parietal cell antibodies (PCA) were fund in 8 (5.4%) out of 147 diabetic children screened. Both sexes were equally represented, but the titres were higher in the girls. No clear relationship between the presence of these antibodies and age or the duration of diabetes was observed. Gastric studies were performed on 8 children with PCA (group A) and 41 without PCA (group B). Both basal (BAO) and maximal acid output (MAO) were significantly (p < 0.05) lower and fasting serum gastrin elevated (p < 0.01) in group A as compared with the control group. Two patients were achlorhydric. In group B, 17 patients out of the 41 studied had hyposecretion and one achlorhydria. The result became most obvious in the group with a duration and diabetes over 10 years, where MAO was significantly diminished (p < 0.05). Gastric morphology revealed atrophic gastritis in 3 patients from seven biopsies in group A and one out five biopsies for severe hyposecretion in group B. Two other children in group A had superficial gastritis. Serum ferritin levels decreased along with the duration of diabetes. Those with gastric mucosa had the lowest values.

Topics: Adolescent; Autoantibodies; Child; Child, Preschool; Diabetes Mellitus, Type 1; Female; Ferritins; Gastric Juice; Gastric Mucosa; Gastrins; Humans; Male; Time Factors; Vitamin B 12

In 11 juvenile diabetics and 13 control subjects, the secretin-pancreozymin test was performed. Duodenal-volume losses were corrected by use of radioactive vitamin B12 as marker substance. As compared to normal subjects, juvenile diabetics had significantly decreased pancreatic outputs of amylase, trypsin, chymotrypsin, and to a lesser degree, of bicarbonate. Clinical evidence of disease of the exocrine pancreas was missing. There was no discernible relationship between the abnormality of external pancreatic function and the duration of diabetes mellitus or the dose of insulin required. Possible factors that may be responsible for the exocrine deficiency of the pancreas in juvenile diabetics are discussed.

Topics: Adult; Amylases; Animals; Bicarbonates; Cholecystokinin; Chymotrypsin; Cobalt Radioisotopes; Diabetes Mellitus, Type 1; Female; Humans; Insulin; Male; Pancreas; Pancreatic Juice; Rats; Secretin; Trypsin; Vitamin B 12

Topics: Adolescent; Adult; Amylases; Bicarbonates; Cholecystokinin; Chronic Disease; Chymotrypsin; Clinical Enzyme Tests; Cobalt Radioisotopes; Diabetes Mellitus, Type 1; Female; Humans; Injections, Intravenous; Lipase; Male; Pancreatic Diseases; Pancreatitis; Proteins; Secretin; Trypsin; Vitamin B 12

Topics: Adolescent; Diabetes Mellitus, Type 1; Diabetic Neuropathies; Female; Humans; Vitamin B 12

Topics: Adolescent; Child; Child, Preschool; Diabetes Mellitus, Type 1; Diet, Diabetic; Humans; Infant; Insulin; Vitamin B 12

Topics: Absorption; Biopsy; Celiac Disease; Cobalt Isotopes; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetic Neuropathies; Diagnosis, Differential; Feces; Humans; Intestine, Small; Intestines; Iodine Isotopes; Lipid Metabolism; Pathology; Steatorrhea; Triolein; Vitamin B 12