Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Besides the obvious toxicity of overdosage and hypoglycemia, insulin administration may also be complicated by a variety of local cutaneous reactions and systemic allergic complications. Although these responses are by no means universal among patients injecting insulin, they may pose significant clinical problems. This is particularly true for the localized skin reactions such as lipoatrophy and the systemic insulin allergy leading to insulin resistance. Most commercially available insulin preparations are extracts of pork or beef pancreas. One approach to reducing insulin complications is to improve the homogeneity of commercial preparations by further purification, which has been afforded by recent technology. A priori, the preparations most resembling human insulin with the fewest contaminants should provide the optimal therapy for diabetic patients. Whether this will prove to be the case remains to be documented.
Diabetes Care
PMID:The role of insulin purification: an overview. 676 17

The large-scale clinical trials of human insulin (recombinant DNA) in the United States consisted of a "New Patient" study and a "Transfer" study. The "New Patient" study involved 101 patients (38% type I) who have never received insulin and who were treated with human insulin and followed for 6 mo using NPH insulin alone or in combination with Neutral Regular Insulin (NRI). Shortly after treatment, serum glucose and total glycohemoglobin concentration fell. No patients developed insulin lipoatrophy or insulin allergy. Two patients developed insulin hypertrophy; in one, it was transient. Intradermal tests to varying dilutions of human insulin did not change over 6 mo. In addition, there was no evidence of development of antibodies to Escherichia coli polypeptide. Two-hundred-and-forty-three patients, 91% of whom had type I diabetes, were transferred in a controlled double-blind study from mixed beef-pork or purified pork insulin (PPI) either to human insulin or back to their previous insulin treatment and followed for 3 mo. While insulin dosage did not change, there was a slight increase in fasting serum glucose and a statistically significant increase in fasting ketonuria. There was no change in the frequency of the complications of insulin treatment. These limited data are consistent with the conclusion that NPH human insulin is slightly shorter acting than its animal insulin counterparts. Overall, human insulin is a safe, effective insulin.
Diabetes Care
PMID:The U.S. "new patient" and "transfer" studies. 676 25

A patient with Werner's syndrome, partial lipoatrophy and diabetes mellitus presented several of the metabolic alterations found in obesity and maturity-onset diabetes, in spite of a total body-fat mass which was markedly reduced when compared to randomly-selected women. The data show elevated blood sugar and free fatty acids, hyperinsulinemia, elevated glucaon and suppressed growth-hormone levels. Metabolic studies with isolated adipocytes show evidence of increased lipolytic response to catecholamines, diminished binding of insulin and decreased antilipolytic effect of this hormone. A striking feature of this patient's adipose tissue was the contrast between lipoatrophy in the subcutaneous tissue of the extremities and augmented abdominatl subcutaneous adipose tissue. The adipocyte size in this region was very large (1.6 micrograms lipid/cell) and among the largest ever recorded in this laboratory. It is proposed that a 'regional adiposity', particularly in the abdominal area, with enhanced adipocyte size and adipocyte metabolic contributions, may promote the metabolic events and alterations that are more typically observed in the generalized form of obesity.
 ...
PMID:Possible systemic metabolic effects of regional adiposity in a patient with Werner's syndrome. 699 62

Physicochemically, NPH and lente insulins differ in size of crystals, content of protamine and zinc, and often in species composition, since lente always contains beef insulin. The duration of the hypoglycemic effect of lente insulin seems to be longer than 24 h, whereas that of NPH insulin does not exceed 24 h when given in amounts of 0.2-0.3 U/kg body wt. Moreover, NPH and lente insulins differ in their ability to form stable mixtures with neutral insulin solutions, since only NPH insulin can be mixed with regular insulin without changing the specific course of effect of regular insulin. Highly purified porcine NPH and the lente-like porcine insulin preparation. Monotard, do not seem to differ regarding side effects (lipoatrophy, immunogenicity). However, highly purified lente insulin (containing beef insulin) seems to be more immunogenic than highly purified porcine NPH insulin.
Diabetes Care
PMID:Intermediate-acting insulin preparations: NPH and lente. 719 5

We report the case of a 13-year-old boy with SHORT syndrome, including lipoatrophy and insulin resistance, who developed diabetes mellitus while receiving growth hormone therapy. The diabetes persisted after cessation of exogenous growth hormone but oral hypoglycaemic therapy was successful and could be discontinued eight months later.
 ...
PMID:Insulin-resistant diabetes during growth hormone therapy in a child with SHORT syndrome. 794 17

Insulin antibodies (IA) are detectable in the sera of most insulin-treated patients with diabetes mellitus. Antibodies to exogenous insulin sometimes cause clinical symptoms of insulin resistance, allergy, and local lipoatrophy. Although the frequency of these complications has diminished with the use of highly purified porcine insulin or recombinant human insulin, there are some patients with high titer of IA. Autoantibodies to insulin (IAA) are also described. IAA has been reported to be in association with both insulin-dependent diabetes mellitus (IDDM) and polyendocrine autoimmune disease. For many years these antibodies have been measured by radiobinding assay (RBA) in which the complexes are precipitated non-specifically by polyethylene glycol. In the present study we developed a rapid and quantitative enzyme-linked immunosorbent assay (ELISA) method for measuring IA and IAA using recombinant human insulin antigen. We applied this method to the samples obtained from patients with diabetes mellitus and autoimmune thyroid disease and then compared the results with those obtained from the RBA method. The calibration curve for ELISA was derived from the dilution curve of a single serum from a patient positive for insulin antibody, and the results were expressed arbitrarily as ELISA UNIT. The calibration curve was approximately linear on the log-log scale within the range of 0.1-2.0 at optical density (OD)450nm, (6.25-200 ELISA UNIT). The intra-assay (CV = 2.3-3.1%) and inter-assay (CV = 2.8-7.2%) precisions were acceptable. Recovery rate varied from 74.5% to 118.5% and dilution experiments showed good linearity. Specificity was demonstrated by substituting purified human IgG for the test serum and glucagon for insulin. Except for hemoglobin, coexisting substances in serum had almost no effect on ELISA. The range of ELISA UNIT (Mean +/- SD) of 83 normal sera was 12.7 +/- 4.6. Positivity for IA by ELISA (> normal Mean + 3SD) was 11 out of 58 (19.0%) and 26 out of 55 (47.3%) in patients with IDDM and with non-insulin-dependent diabetes mellitus (NIDDM) who were treated with insulin, respectively. Positivity for IAA by ELISA was 5 out of 173 (2.8%) and 1 out of 20 (5.0%) in patients with NIDDM without insulin therapy and hyperthyroidism due to Graves' disease, respectively. However, by RBA, we detected 4 other cases positive for IAA in NIDDM without insulin therapy and one case in Graves' disease. The present study demonstrates that the newly developed method of ELISA using recombinant human insulin antigen is clinically useful for measuring IA and IAA.
 ...
PMID:[The measurement of insulin antibodies and insulin autoantibodies by enzyme-linked immunosorbent assay using recombinant human insulin antigen and its clinical application]. 795 8

Immunological complications of insulin therapy have been evident since animal insulins became available for the treatment of diabetes mellitus in 1922. Insulin allergy has been particularly common, with local symptoms still occurring in approximately 5% of all patients. Insulin antibodies of high titers were observed in many patients treated with early insulin preparations containing proinsulin, C-peptide, and other peptide contaminants. Immunoglobulin G-insulin antibodies of very high levels can lead to immune-mediated insulin resistance, which is now extremely rare because of the widespread use of highly purified porcine insulin and human insulin preparations. Lipoatrophy, which was reported in 10-55% of patients treated with nonpurified bovine/porcine insulin preparations, has almost disappeared in patients since the advent of exclusive human insulin treatment. In view of the wide spectrum of immune-mediated complications of insulin therapy, much attention has been directed to the reduced immunogenicity and allergenicity of highly purified porcine insulins and the more recently available recombinant and semisynthetic human insulin preparations. Insulin antibodies of the immunoglobulin G and immunoglobulin E type can develop, however, in very low titers in patients treated exclusively with human insulin. Frequency and levels of immunoglobulin G insulin antibodies are identical in patients treated either with biosynthetic or semisynthetic human insulin preparations. Allergic symptoms to human insulin are now found in < 1% of de novo-treated patients, but still may occur when human insulin is used in the insulin-allergic patient. In summary, immunological complications of insulin therapy have decreased significantly during the last two decades and are now predominantly observed in patients with interrupted insulin therapy.
Diabetes Care 1993 Dec
PMID:Immunogenicity and allergenic potential of animal and human insulins. 829 72

Insulin resistance is present in patients suffering from lipoatrophic syndromes long before the onset of diabetes mellitus. Thus, the decreased peripheral glucose disposal may not be the only mechanism of hyperglycaemia. The kinetic parameters of glucose homeostasis were evaluated in six young females aged 15, 16, 18, 19 and 24 years with generalized lipoatrophy; one patient was studied both at 12 and 15 years. Insulin resistance was evaluated in vivo by the hyperinsulinaemic euglycaemic clamp (3-4 insulin infusion rates from 1 to 100 mU/kg.min). All patients showed a rightward shift of the dose-response curve, indicating decreased insulin sensitivity. In two patients, maximal glucose disposal was moderately decreased, while in five patients it was dramatically reduced (3.6-6.9 mg/kg.min). Fasting plasma glucose was variable (4.3-18.3 mmol/l) and did not correlate with peripheral glucose disposal rates. Hepatic glucose production, measured by infusion of [6,6-2H] glucose, varied from 1.7 to 8.3 mg/kg.min and was significantly correlated with fasting plasma glucose. The overproduction of glucose despite basal hyperinsulinism suggested hepatic insulin resistance, which was confirmed by the abnormal response to constant unlabelled glucose infusion (2 mg/kg.min) in five patients. In conclusion, impaired glucose tolerance seems to develop in generalized lipoatrophy with aggravated peripheral insulin resistance. The present data show that fasting hyperglycaemia is mainly the consequence of increased hepatic glucose production.
 ...
PMID:The development of hyperglycaemia in patients with insulin-resistant generalized lipoatrophic syndromes. 830 57

Using the molecular scanning technique of single-stranded conformational polymorphism (SSCP), we have examined the exons encoding the insulin receptor gene in 26 patients with syndromes of insulin resistance. We found 27 variant sequences, 4 of which were mutations that altered an amino acid. One patient with the Rabson-Mendenhall syndrome was homozygous for a mutation in the extracellular alpha-subunit (Ser to Leu323), one type A insulin-resistant patient was heterozygous for Pro to Leu1178, and another type A insulin-resistant patient was heterozygous for a mutation in the COOH-terminus of the receptor (Arg to Gln1351). The previously reported, and probably functionally insignificant, variant Val to Met985 was detected in one patient. No missense or nonsense insulin receptor mutations were found in any patients whose insulin resistance was associated with gross obesity, lipoatrophy, or acromegaloid features. No missense or nonsense mutations were found in subjects with polycystic ovary syndrome or Syndrome X. Putting these findings in the context of other work in this field, we conclude that subjects with leprechaunism or Rabson-Mendenhall syndrome have a high probability of having a missense or nonsense insulin receptor mutation. Nonobese, nondysmorphic, severely insulin-resistant females with hirsutism, acanthosis nigricans, and menstrual disturbance (type A phenotype) have an intermediate probability of having this type of insulin receptor mutation. Although insulin receptor mutations have been occasionally described in other phenotypes of insulin resistance, the frequency of point mutations in the exons of the insulin receptor gene in patients with those phenotypes appears to be low.
Diabetes 1994 Mar
PMID:Molecular scanning of the insulin receptor gene in syndromes of insulin resistance. 831 8

We describe a case of lipoatrophy that was secondary to human insulin. The patient had only ever been treated with human insulin, and the lipoatrophy appeared to partially resolve with continued use of the same insulin preparations. Possible underlying pathogenic mechanisms are discussed.
Diabetes Care 1996 Nov
PMID:Lipoatrophy with human insulin. 890 98


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>