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Query: UMLS:C0011849 (diabetes)
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We observed three children with a clinically similar presentation of erythematous nodules that expanded centrifugally leaving lipoatrophy. Areas of lipoatrophy coalesced, resulting in clinical pictures similar to partial or total lipodystrophy. Histologic study revealed a lobular panniculitis with a mixed infiltrate of lymphocytes and mononuclear phagocytes. Of these three children, one had insulin-dependent diabetes mellitus and Hashimoto's thyroiditis, one developed juvenile rheumatoid arthritis, and the third developed insulin-dependent diabetes mellitus, suggesting that the pathogenic mechanism may be an expression of autoimmunity.
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PMID:Lipoatrophic panniculitis: a possible autoimmune inflammatory disease of fat. Report of three cases. 368 6

Treatment with conventional insulin preparations results in appreciable insulin antibody formation in nearly all subjects. High titers of insulin antibodies are undesirable. They might induce insulin allergy and insulin resistance, and they influence metabolic regulation. Also, lipoatrophy is related to the immunogenicity of insulin preparations. Insulin antibodies are transferred from insulin-treated diabetic mothers to the fetus and contribute to the increase of free plasma insulin in the fetus, thus influencing the development of macrosomia and neonatal hypoglycemia. Therefore, the risk of insulin antibody formation should be reduced. This is possible by using purified, nonbeef insulin preparations. The risk of insulin allergy, insulin resistance, lipoatrophy, and prolonged hypoglycemia in mother and child is reduced by treating pregnant diabetic subjects with purified pork or human insulin preparations. The reduction of insulin requirement that accompanies the change from conventional insulin to purified nonbeef insulin treatment will compensate to some extent for the higher costs of new insulins.
Diabetes 1985 Jun
PMID:The immunogenicity of new insulins. 388 48

Twenty-six Type 1 diabetic patients previously treated for 10-20 months with twice daily conventional bovine isophane insulin (containing at least 1000 ppm proinsulin) were changed to highly purified (less than 1 ppm proinsulin) bovine isophane for 6 months (Switch group). Insulin antibody levels fell significantly from a geometric mean of 14.9 to 9.1 micrograms/l. Thirty-two patients with newly diagnosed Type 1 diabetes were treated with the same highly purified bovine isophane insulin twice daily for 6 months (Starter group). Their insulin antibody levels rose from a geometric mean of 1.9 to 8.2 micrograms/l in contrast to values of 1.4 rising to 16.3 micrograms/l in an age and sex matched historical control group treated from diagnosis only with twice daily conventional bovine isophane insulin. Lipoatrophy at injection sites developed in three (9%) in the Starter group treated with highly purified bovine isophane compared to 7 (22%) of those on conventional bovine isophane. Insulin dose and diabetic control did not differ between the groups. Starter and Switch groups were subsequently treated with semi-synthetic human isophane insulin for 6 months during which insulin antibody levels fell significantly from a geometric mean of 8.5 to 4.4 micrograms/l (p less than 0.001). We conclude that bovine insulin purified to less than 1 ppm proinsulin is significantly less immunogenic than its conventional proinsulin contaminated counterpart but even at this level of purity is still more immunogenic than human insulin of equivalent purity.
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PMID:Immunogenicity of highly purified bovine insulin: a comparison with conventional bovine and highly purified human insulins. 390 77

Nineteen children with insulin-dependent diabetes mellitus in the University Department of Paediatrics were assessed for complications of diabetes. 36.8% showed marked growth stunting, and half of the patients who attained puberty had a delayed onset of puberty. 42% showed limited joint mobility. Almost all the patients developed hypertrophic lipodystrophy while only 5 patients developed reversible lipoatrophy. Abnormal nerve conduction velocities were found in all 17 patients tested, with more of sensory nerve involvement. A significant correlation was found between duration of disease and the extent of neuropathy. Evidence of nephropathy was found in 5 patients, 2 of whom showed impaired renal function. One patient had background retinopathy, another had proliferative retinopathy and 2 patients developed cataracts. The high prevalence of microangiopathic complications in these children is probably related to their previous poor diabetic control and it is hoped that with home blood glucose monitoring to improve their control, these complications may be arrested or minimized.
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PMID:Assessment of complications in children with insulin-dependent diabetes mellitus. 403 84

Patients treated with insulin can develop a variety of adverse cutaneous and subcutaneous reactions localized at sites of insulin injection. The reported frequency, severity, and type of skin reactions to insulin are varied, as are the theories relating to their etiology and recommendations for treatment. In this review, several types of localized skin reactions to insulin injection will be described. Particular attention will be devoted to insulin lipoatrophy and skin reactions in patients using mechanical devices for continuous subcutaneous insulin infusion. Recent advances in diabetes care have made insulin-induced lipoatrophy a preventable and treatable disorder. However, localized skin reactions are emerging as a potential problem among users of insulin infusion pumps.
Diabetes Care
PMID:Localized skin reactions to insulin: insulin lipodystrophies and skin reactions to pumped subcutaneous insulin therapy. 623 Nov 69

Insulin resistance is a permanent feature of lipoatrophic diabetes, the resistance being almost regularly stubborn. We report the case of a 23-year old unmarried woman with generalized lipoatrophy and Acanthosis nigricans. Seven years after a diabetes resistant to all treatments was diagnosed, blood glucose levels were permanently around 25 mmol/l. Multiple and severe micro- and macroangiopathies were present. Partial resistance to insulin was demonstrated. This resistance could not be explained by abnormalities in anti-insulin hormones nor by a decrease in the number or affinity of insulin receptors, which suggested an intracellular abnormality below membrane receptors. Sustained control of glycaemia at a normal level was achieved by continuous infusion of insulin in high doses. It would appear that optimum insulin therapy using an insulin pump would offer hopes of therapeutic success in this particular form of insulin resistance.
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PMID:[Lipoatrophic diabetes with acanthosis nigricans. Prolonged blood glucose normalization by continuous infusion of insulin]. 623 27

A new case of lipoatrophic diabetes with some peculiar features is reported. The disease was acquired, with onset at approximately thirty years of age, and partial, involving only the face and the upper limbs. The authors were able to observe the successive occurrence of the various symptoms: progressive lipoatrophy, hyperinsulinism, insulin-resistant diabetes, major lipid disturbances, and finally renal failure with a nephrotic syndrome and high blood pressure. Nosologic borders and physiopathology are discussed with a review of the literature.
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PMID:[Partial progressive lipoatrophy. A new case-report (author's transl)]. 627 48

Fifty-one insulin-dependent diabetic patients, 26 children and 25 adults, participated in an open uncontrolled study of the safety and efficacy of human insulin (Novo). The patients, who had previously been treated exclusively with porcine insulin, were followed in two outpatient clinics during a 3-mo study period. During the study period the patients' mean insulin dose and postprandial blood glucose level, as well as the number of hypoglycemic episodes, did not change. The level of hemoglobin A1c was unchanged in the children but fell in the adult patients. None of the patients developed lipoatrophy or experienced any allergy or adverse reaction. One patient died of causes unrelated to the diabetes. Mean insulin-binding IgG did not change during the 3-mo study period. After 12 mo of treatment no significant differences were found between the mean level of insulin-binding IgG in patients who had continued treatment with human insulin and patients who had resumed treatment with porcine insulin after the 3-mo study period. It is concluded within the framework of this study that human insulin is safe and that no major differences in metabolic effect between purified porcine insulin and human insulin could be demonstrated. Thus, patients can be transferred from purified porcine insulin to human insulin without any special precautions.
Diabetes Care
PMID:The efficacy and safety of human insulin (Novo) in insulin-dependent diabetic patients. 634 40

The literature of the past ten years shows that the introduction of highly purified heterologous and, lastly, homologous insulins has notably lowered the production of IgG and IgE specific insulin antibodies, but has not succeeded in completely eliminating clinical manifestations of the immune or hyper-immune response to insulin therapy. In particular, insulin allergy with or without lipodystrophy is still seen. Among the factors of insulin immunogenicity, there is a possible genetic control of the immune response in type I diabetes: determining HLA halloantigens (A, B, C, D) might identify specific immune response genes (Ir genes). Initial researches, performed until now almost exclusively upon diabetics treated with conventional heterologous insulin, seem to indicate a positive relationship between haplotype HLA - B15 - DR4 and an elevated immune response, whereas haplotypes HLA - B8 - DR3 and HLA - B18 - DR3 might protect against the formation of anti-insulin antibodies. Antigens D/DR3 and D/DR4 are known to be primitively associated to susceptibility for type I diabetes, whereas antigens B8, B15, B18 are secondarily associated to the rise in frequency of DR3 and DR4 for the "linkage disequilibrium" existing between alleles of B and D loci. The results of HLA typing are presented in 2 groups of insulin-dependent diabetics (ID) followed from an immunological viewpoint during therapy with monocomponent heterologous insulin for over 5 years. The first group is composed of 50 patients with low IgG anti-insulin antibody titers (less than 1 mU/ml, Christiansen: low responders); the second group is made up of 23 patients with high IgG anti-insulin antibody titers (greater than 2.5 mU/ml, Christiansen: high responders) and includes 5 subjects with insulin allergy (associated or not with insulin lipoatrophy) and high levels of insulin specific IgE antibodies. A study of the frequencies of various HLA-B antigens in both groups of patients, in regard to a control group of piemontese population, in relation to the intensity of association (relative risk) and to the statistical importance of frequencies, shows only a possible protective effect of the HLA-B18 phenotype (linkage disequilibrium with HLA - DR3) towards the production of anti-insulin antibodies and hyperimmune clinical manifestations, such as allergy. Reliable conclusions are not possible between low and high responders for the other phenotypes (HLA - B7, B8, B15) commonly implicated. HLA-B12 was noted in 3 of 5 patients with allergy, in 2 cases associated with B8.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[HLA typing and insulin antibody production in insulin-dependent diabetics]. 644 4

Many skin lesions are specific for diabetes mellitus. Necrobiosis lipoidica, lipoatrophy and idiopathic bullae (bullosis diabeticorum) are usually associated with diabetes. However, diabetic scleredema has not been noticed by internists, although dermatologists have paid attention to such a cutaneous manifestation. We reported a clinical case of a female diabetic patient aged 15 who had been afflicted with diabetic scleredema. She had been treated with insulin since 5 years of age. She noticed stiffness of the skin in April 1980. Skin biopsy showed thickness of the dermis and accumulation of acid mucopolysaccharide. After control of blood glucose with continuous subcutaneous insulin infusion (CSII) and administration of tocopherol acetate and hyaluronidase, the skin lesion improved. Etiology of diabetic scleredema is unknown. Such skin lesion which is observed frequently in insulin dependent obese patients is different from a category of scleredema of Buschke.
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PMID:Diabetic scleredema. 667 Jan 1


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