Potential cause-effect relationship between insulin autoimmune syndrome and alpha lipoic acid: Two case reports.

OBJECTIVES: Insulin autoimmune syndrome (IAS) or Hirata disease is a rare cause of autoimmune hypoglycemia with apparent high insulin levels and anti-insulin autoantibodies and was first described by Hirata in Japan in 1970. IAS cases are usually related to exposure to sulfhydryl-containing drugs, which stimulate the production of insulin autoantibodies. Among sulfhydryl-containing compounds, alpha lipoic acid (ALA) has recently emerged as a cause of IAS. After the first observations of ALA-induced IAS were reported in Japan in 2006, an increasing number of cases related to ALA administration have been described. An Italian group recently reported on six cases of IAS of which one was associated with HLA-DRB1*04:06 and the remaining five with HLA-DRB1*04:03. This suggests that the latter is potentially involved in the genetic susceptibility of people of European descent to IAS. METHODS: Here, we describe two new cases of IAS in women that were triggered by ALA. RESULTS: Both cases are associated with HLA-DRB1*04:03 and confirm the evidence that HLA-DRB1*04:03 rather than HLA-DRB1*04:06 is specifically related to IAS susceptibility in Europeans. CONCLUSIONS: Case reports of ALA-induced hypoglycemic episodes highlight the need for greater care in prescribing ALA supplementation as well as the identification of specific and personalized therapeutic targets.

Medical Nutrition Therapy Is Effective in the Management of Hypoglycemia Caused by Insulin Antibodies: A Case Report and Literature Review.

Autoimmune antibodies, induced by exogenous insulin preparations, may result in labile glucose control and frequent hypoglycemia in some rare cases. In addition to insulin cessation, immune suppressants and/or plasmapheresis have been used as the primary remedies for these patients. Some previous studies also indicate that the condition tends to remit spontaneously after discontinuation of insulin exposure. Because of this, the clinical importance of nutritional interventions and behavioral approaches, which may play a role in ameliorating the symptoms, should also be emphasized. Herein, we report on a 64-year-old man with hypoglycemia induced by insulin antibodies (IAs), whose hypoglycemic symptoms significantly improved after the implementation of nutrition therapy. This rare case expands our knowledge of the management of hypoglycemia, and for the first time highlights the significance of nutritional and lifestyle intervention in treatment of IA-induced hypoglycemia.

Hydrothermally modified slow release corn starch: a potential new therapeutic option for treating hypoglycemia in autoimmune hypoglycemia (Hirata's disease).

We report the successful treatment of autoimmune hypoglycemia in an 82-year-old non-diabetic Caucasian male with hydrothermally modified slow release corn starch, a product which is used in other conditions associated with hypoglycemia, most typically glycogen storage disease type I. An 82-year-old-Caucasian male presented with recurrent spontaneous hypoglycemia as low as 30 mg/dl following in-patient treatment for community acquired pneumonia. During a fasting-test, symptomatic hypoglycemia occurred. Plasma concentrations of c-peptide and insulin were considerably elevated. Autoimmune hypoglycemia was confirmed by the presence of insulin autoantibodies. While dietary restriction alone did not result in sufficient glucose control in this patient with autoimmune hypoglycemia, treatment with hydrothermally modified slow release corn starch led to stable euglycemia. This easy, well tolerated and non-invasive treatment may constitute a new therapeutic option for hypoglycemia in patients with autoimmune hypoglycemia who do not achieve sufficient control of hypoglycemia by dietary restriction alone.

Insulin autoimmune syndrome in a health supplement user: the effectiveness of cornstarch therapy for treating hypoglycemia.

A 70-year-old woman with no history of diabetes was admitted to the hospital for the management of hypoglycemia. Her fasting plasma glucose level was 54 mg/dL with an extremely high serum immunoreactive insulin level (1210 µU/mL). She had high titers of anti-insulin antibodies and exhibited the DRB1*0406 genotype for HLA-DR4, leading to a diagnosis of insulin autoimmune syndrome. She had been taking several health preparations for approximately 10 years; however, all were thiol group-free. Due to frequent episodes of nocturnal hypoglycemia, the health preparations were discontinued and the patient was treated with cornstarch. This protocol successfully ameliorated the hypoglycemic episodes and normalized the patient's laboratory and serological test results.

Influence of early nutritional components on the development of murine autoimmune diabetes.

BACKGROUND/AIMS: Infant diet is suggested to modify autoimmune diabetes risk. The aim of this study was to determine whether infant food components affect diabetes development in the nonobese autoimmune diabetes (NOD) mouse. METHODS: A basal low-diabetogenic diet was identified by feeding litter-matched female NOD mice standardized diets with and without casein and wheat proteins after weaning. In subsequent trials, basal diet with supplements of wheat (5, 10 and 30%), gluten, wheat globulin/albumin, corn (5%), potato (5%), apple (5%) or carrot (5%) was fed to litter-matched female NOD mice after weaning. Mice were followed for diabetes development and insulin autoantibodies. RESULTS: A casein- and wheat-free diet was associated with the lowest rate of diabetes development (37% by age 25 weeks). Increased diabetes rates were observed when the basal diet was supplemented with 5% wheat (71% by age 25 weeks; p = 0.023) and 5% corn (57% by age 25 weeks; p = 0.05). Increasing wheat concentrations returned diabetes development to that in basal diet-fed mice. Other food supplements had no or minimal effects on diabetes development. CONCLUSIONS: Early supplementation of a basal low-diabetogenic diet with low concentrations of the cereals wheat or corn is associated with a moderate increase in the rate of diabetes. Removal of cereals, however, does not abrogate diabetes development in NOD mice.

[Effects of acupuncture on serum insulin antibody and tumor necrosis factor alpha in the experimental rat with insulin resistance].

OBJECTIVE: To observe effects of acupuncture and diet on insulin resistance (IR) and to probe the mechanism. METHODS: Forty SID rats were equally divided into 5 groups: blank group (group I), model group I (group II), model group II (group III), acupuncture group I (group IV) and acupuncture group II (group V). The groups II, III, N and V were fed with high-fat-sugar-salt forage to made IR model, then the groups I, III and V were fed with normal forage, and the groups II and IV with the high-fat-sugar-salt forage, and the acupuncture groups IV and V received acupuncture treatment. Two weeks later, the fasting blood glucose (FBG), plasma insulin (INS), insulin sensitivity index (ISI), INS antibody and tumor necrosis factor alpha (TNF-alpha) were detected. RESULTS: As compared with group I, FBG and INS increased, ISI decreased in the group II (all P < 0.01); as compared with the group II , FBG and INS decreased (all P < 0.01) and ISI increased (P < 0.05, P < 0.01) in the group [II, IV, V; no case with INS antibody (+) in all groups; TNF-alpha in the group II increased compared with that of the group I (P < 0.01), and TNF-alpha in the group III, IV, V decreased compared with that of group II (P < 0.01). CONCLUSION: Acupuncture exerts a reversal effect on insulin resistance, and diet can promotes this effect. The mechanism is carried out possibly through decreasing the secretion of TNF-alpha.

[Preliminary study on relationship between TCM syndrome-type and insulin resistance in coronary heart disease].

OBJECTIVE: To observe the relationship between TCM Syndrome-type and insulin resistance (ISR) in coronary heart disease (CHD). METHODS: Fifty patients were divided into 3 groups according to the Syndrome Differentiation-typing in TCM, the Heart blood stasis (HBS) Syndrome group, the Phlegm-Turbid stagnation (PTS) Syndrome group and both Qi-Yin Deficiency (QYD) Syndrome group. The fasting blood glucose (FBG), fasting blood insulin (Ins), insulin antibody (IAA), islet cell antibody (ICA), glutamic acid decarboxylase antibody (GAD-Ab) and related blood lipid parameters in patients were determined and insulin sensitive index (ISI) was calculated simultaneously. Then the above-mentioned data were compared with those determined in 20 healthy control subjects. RESULTS: The levels of FBG and Ins in CHD group were higher than those in healthy control group significantly (P < 0.05), but ISI level was obviously lower (P < 0.01). Moreover, the positive ratio of IAA (40%) was higher in CHD group than that in the control group (5%) significantly (P < 0.01). Comparison between the 3 TCM Syndrome-type groups and the control group showed that ISI level in HBS and PTS group was obviously lower than that in the control and the QYD (P < 0.05) respectively, and the IAA positive ratio in the former 2 groups (50%, 47.3%) was higher than that in the later two (5%, P < 0.01 and 15.38%, P < 0.05) markedly. While Ins level increased only in the HBS group (P < 0.05). Besides, patients of HBS and PTS were accompanied by lipid metabolic disturbance. CONCLUSION: ISR presents in part of CHD patients particularly in those with HBS and PTS, which was partly due to the existence of IAA in patients serum.

Insulin antibodies do not preclude optimization of metabolic control in women with IDDM during pregnancy.

OBJECTIVE: To evaluate whether the presence of insulin antibodies (IAs) may preclude the optimization of metabolic control during pregnancy and affect outcome in women with IDDM. RESEARCH DESIGN AND METHODS: IAs were measured by radiobinding assay in 44 women with IDDM referred to the Diabetes and Pregnancy Outpatients' Clinic during 46 pregnancies. Age, duration of IDDM, metabolic control (HbA1c, mean pre- and postprandial capillary blood glucose, frequency of hypo- or hyperglycemia), insulin requirement at 1st and 3rd trimester of pregnancy, BM1, and weight gain were recorded. Neonatal variables such as gestational age, weight, length, and the presence at birth of either hypoglycemia, hypocalcemia, or jaundice requiring phototherapy were also considered. RESULTS: IAs correlated positively with insulin requirement (P < 0.05) and negatively with HbA1c at term (P < 0.01). Patients with IA levels > or = 40% insulin binding (8 of 46) had a higher insulin requirement and lower preprandial capillary blood glucose at the beginning of pregnancy but not at term (P < 0.005), whereas they had lower HbA1c at term than did patients with low IA levels (P < 0.01). IA levels decreased slightly at term (P = 0.007). IA levels > or = 40% were not associated with a higher rate of hypo- or hyperglycemic episodes or with diabetic complications or thyreopathy. No correlation was found between 1A levels and any of the neonatal variables considered. CONCLUSIONS: The presence of IAs does not preclude optimization of metabolic control during pregnancy and is compatible with a favourable outcome.

[The effect of long-term glibenclamide administration on pancreatic beta cells and on autoimmunity indices]. / Vliianie dlitel'nogo vvedeniia glibenklamida na pankreaticheskie beta-kletki i nekotorye pokazateli autoimmuniteta.

It was found that administration of glybenclamide in the therapeutic dose to rats exerts the damaging effect on insulin-producing apparatus of the pancreas (inhibition of the secretory reaction of beta-cells, disturbance of their morphological structure, decrease of glucose tolerance test), initiates the development of lymphocellular infiltration of islands (autoimmune insulitis), increases the level of antibodies to blood serum DNA. The inverse temporal dependence between the appearance and degree of diabetogenic effects of chronic sulfanylamide therapy and changes in autoimmunity (the latters are characteristic of earlier treatment with the drug) can be traced.