Insulin autoimmune syndrome: idsorders diagnosis to clinical management. Autiommune Information. Disorrders you have children you can model Nut-Free Options healthy lifestyle for them Fiber optic network connectivity solutions Nut-Free Options them to cook Hypoglyfemia themselves as well. Country of Treatment. Human Phenotype Ontology HPO provides standard terminology that was used by Orphanet and OMIM to represent a disease's phenotypic features. TBIRS is a rare autoimmune disorder resulting in a variety of abnormalities in glucose homeostasis, from hypoglycemia to extremely insulin-resistant hyperglycemia, caused by the presence of insulin receptor autoantibodies IRAbs 81 - Takeuchi Y, Miyamoto T, Kakizawa T, Shigematsu S, Hashizume K.

Hypoglycemia and autoimmune disorders -

Contact EDMCR About EDMCR Scope Editorial board Societies For libraries Abstracting and indexing. Advanced Search Help. Authors: Pooja Sahni Pooja Sahni Division on Endocrinology and Metabolic Medicine and Department of Internal Medicine, St Vincent Hospital, Worcester, Massachusetts, USA Search for other papers by Pooja Sahni in Current site Google Scholar PubMed Close.

Nitin Trivedi Nitin Trivedi Division on Endocrinology and Metabolic Medicine and Department of Internal Medicine, St Vincent Hospital, Worcester, Massachusetts, USA Search for other papers by Nitin Trivedi in Current site Google Scholar PubMed Close.

Abdulkadir Omer Abdulkadir Omer Division on Endocrinology and Metabolic Medicine and Department of Internal Medicine, St Vincent Hospital, Worcester, Massachusetts, USA Search for other papers by Abdulkadir Omer in Current site Google Scholar PubMed Close.

Article Type: Research Article Online Publication Date: 11 Oct Open access. Get Citation Alerts. Download PDF. Check for updates. Learning points: Initial assessment of the Whipple criteria is critical to establish the clinical diagnosis of hypoglycemia accurately.

Summary A year-old obese Caucasian woman presented with symptomatic postprandial hypoglycemic episodes, resolution of symptoms with carbohydrate intake and significantly elevated anti-insulin antibody levels.

Keywords: Adult ; Female ; White ; United States ; Pancreas ; Autoimmunity ; Diabetes ; Insulin ; Insulin autoimmune syndrome ; Hypoglycaemia ; Hypoglycaemia ; Sweating ; Headache ; Confusion ; Anti-insulin antibodies ; Glucose blood ; Haemoglobin A1c ; Insulin ; C-peptide blood ; Proinsulin ; Proinsulin ; Diet ; Omeprazole ; Gastroenterology ; Insight into disease pathogenesis or mechanism of therapy ; October ; Background Insulin autoimmune syndrome IAS — a rare cause of autoimmune hypoglycemia — was first described in a study by Hirata et al.

Investigation She was recommended to monitor her blood sugar levels at home and to come to the laboratory when she experiences hypoglycemic symptoms.

Treatment The treatment options were discussed, including nutritional management and corticosteroid use. Outcome and follow-up At six-month follow-up, she reported a decrease in the frequency of hypoglycemia symptoms, occurring only once every month.

Table 1 Laboratory results during initial and subsequent follow-up visits. Declaration of interest The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.

Funding This work did not receive any specific grant from any funding agency in the public, commercial, or not-for-profit sector.

Author contribution statement A Omer diagnosed and followed up the case, organized the data for publication, he and is responsible for accuracy and validity of the data.

PubMed Hirata Y Ishizu H Ouchi N Motomura S Abe M Hara Y Wakasugi H Takahashi I Sakano H Tanaka M Insulin autoimmunity in a case of spontaneous hypoglycemia.

PubMed Chang HJ Choi HS Park MY Leem SM Jang YS Park KS Lee JM A case of insulin autoimmune syndrome related to alpha-lipoic acid. PubMed Uchigata Y Hirata Y Insulin autoimmune syndrome IAS, Hirata disease. In Immunoendocrinology: Scientific and Clinical Aspects, 1st edition, pp — New York : McGraw-Hill false.

Insulin autoimmune syndrome. Country of Treatment. United States. Signs and Symptoms. Anti-insulin antibodies.

C-peptide blood. Glucose blood. Haemoglobin A1c. Case Report Type. Insight into disease pathogenesis or mechanism of therapy. More information is on the Reasons to publish page.

Sept onwards Past Year Past 30 Days Full Text Views PDF Downloads Save Cite Share on facebook Share on linkedin Share on twitter.

Related Articles. Summary Learning points: Background Case presentation Investigation Treatment Outcome and follow-up Discussion Declaration of interest Funding Patient consent Author contribution statement. Copyright: This is an Open Access article distributed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.

Export References. ris ProCite. bib BibTeX. enw EndNote. PubMed Citation Article by Pooja Sahni Article by Nitin Trivedi Article by Abdulkadir Omer Similar articles in PubMed. Article by Pooja Sahni Article by Nitin Trivedi Article by Abdulkadir Omer Similar articles in Google Scholar.

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One of the functions of cortisol is stabilizing blood sugar while in the fasting state as in when you are asleep. Problems with sleep, such as issues falling back to sleep if you wake in the middle of the night or early morning, can sometimes be a direct result of blood sugar dysfunction and cortisol surges.

Therefore, not only can issues with sleep reflect possible blood sugar issues, but by fixing underlying blood sugar issues, you can fix your sleep. Not only does blood sugar affect sleep, but sleep directly affects blood sugar. It has been shown that lack of sleep increases blood sugar!

If you tend to get low blood sugars, sometimes a low-glycemic snack before bed, such as unsweetened plantain chips or a handful of nuts, can help keep your blood sugar more stable.

If you tend to wake up in the middle of the night and have a hard time falling back to sleep, you can simply keep a handful of grapes on your nightstand and eat them upon waking, which can help you go back to sleep quicker.

To promote better sleep, go to bed at the same time every night and wake up at the same time every morning. This simple routine can drastically help your cortisol and blood sugar levels stay more consistent.

Finally, avoid a sedentary lifestyle. Staying physically active instead of a couch potato is an important key to blood sugar stability. Commit to exercising consistently, at least four days a week. Consistent exercise will improve not only control of your blood sugar and insulin levels, but it will also help improve your cardiovascular health.

All of this leads to improved stress management. As we all know, when we exercise, the body releases chemicals called endorphins. Endorphins interact with brain receptors to reduce our perception of pain and trigger positive feelings in the body. Endorphins can alleviate depression, a common symptom for lupus patients, and reduce stress and anxiety.

Find your level of exercise tolerance and keep a journal of type of exercise, time, intensity, and how you feel. Do whatever gets you up, active and moving, and make it a habit! There are a number of nutrients that help address insulin resistance and blood sugar dysregulation.

These nutrients bolster and support a healthy diet and lifestyle to specifically address the unhealthy use of blood sugar in the body. The following list of nutrients helps with blood sugar stability and insulin receptor sensitivity, which is key in reversing insulin resistance and diabetes.

A number of nutraceuticals are made up of synergistic blends of these nutrients that target insulin resistance. Cookbooks, recipes, and online cooking sites can be amazing tools — KEYS to fueling delicious lifestyle changes and controlling your blood sugar.

Millions of people struggling with blood sugar suffer from autoimmunity, whether they know it or not, and it is often the root cause of weight gain, brain and mood problems, fatigue, and often can take years—or even decades—for symptoms and a clear diagnosis to arise.

Recipes can be your entry point to recovery. And furthermore, cooking has other benefits besides just supporting you in putting healthy food into your body.

Cooking can be very relaxing and the very task of cooking can help to reduce stress levels. You can develop a love of cooking de-stress while creating healthy and delicious foods that will go a long way in helping you to heal, recover and get your life back.

If you have children you can model a healthy lifestyle for them and teach them to cook for themselves as well. If you already have a love of cooking, you can re-learn a healthier way to cook and enjoy the creativity and ingenuity that can help you to stabilize your blood sugar, improve your sleep, and support your body in healing itself.

If oral nutrition is impossible, or during longer fasting periods i. Patients with more severe IAS may also benefit from continuous glucose monitoring to help predict and promptly respond to falling blood glucose levels 68 , A specific treatment is required for the few patients whose hypoglycemia is more severe Acarbose is an α-glucosidase inhibitor used to treat reactive idiopathic postprandial hyperinsulinemic hypoglycemia episodes as it is able to delay carbohydrate absorption Acarbose can be used in IAS to dampen the postprandial rise in serum glucose and insulin, but it is poorly tolerated due to adverse gastrointestinal effects such as diarrhea and flatus.

Since severe refractory autoimmune hypoglycemia is an autoimmune-based condition, it has also been treated with high-dose corticosteroids, such as prednisone, with good results in terms of both glycemic control and IAA titers 26 , Plasmapheresis has also been widely used, alone or in combination with corticosteroids in more severe cases, to control hypoglycemic symptoms and lower IAA titers more rapidly 26 , Plasmapheresis alone is especially useful when glucocorticoids are contraindicated Rituximab has recently been introduced for the treatment of many patients with life-threatening hypoglycemia and refractory to high-dose corticosteroids 69 , 73 - It also improved the outcome of a patient with DM-1 who developed IAA to exogenous insulin The treatment of IAS in the context of a myeloma and MGUS is particularly challenging.

Patients need to take numerous small meals and keep to a diet low in simple sugars, probably for life, and they must learn how to recognize and treat their hypoglycemia episodes. In some cases, hypoglycemic crises are severe enough to necessitate plasmapheresis, glucocorticoids, and even chemotherapy, in an effort to reduce the levels of anti-insulin-binding monoclonal immunoglobulins The levels of IAA and the severity of the symptoms sometimes parallel the remission-relapse phases of myeloma.

Insulin resistance syndromes include a broad array of disorders characterized by insulin resistance and a consequently increased β-cell insulin secretion. Among the different types of insulin resistance syndrome, the genetically-determined forms comprise numerous syndromes related to an insulin receptor or insulin receptor signal impairment [type A insulin resistance syndrome OMIM , Rabson-Mendehall syndrome OMIM , leprechaunism OMIM , lipodystrophy OMIM ] 77 , These syndromes generally manifest at birth or in infancy and early childhood with extreme insulin resistance, growth retardation, acanthosis nigricans, hirsutism, and polycystic ovarian disease in patients who are not usually obese.

Hyperandrogenism HA , insulin resistance IR , and acanthosis nigricans AN characterize HAIR-AN syndrome, which becomes manifest in obese, anovulatory women, and is considered a form of polycystic ovary syndrome PCOS Insulin type-B resistance syndrome TBIRS was first reported by Kahn et al.

in 77 , and the same authors subsequently demonstrated that it is due to circulating antibodies that block the membrane receptors for insulin 79 , TBIRS is a rare autoimmune disorder resulting in a variety of abnormalities in glucose homeostasis, from hypoglycemia to extremely insulin-resistant hyperglycemia, caused by the presence of insulin receptor autoantibodies IRAbs 81 - The exact prevalence of TBIRS is not known, but it is quite rare As at , only 67 cases had been reported worldwide 82 , The median clinical age at onset is 39 years range, 15—64 years in females, and 56 years in males range, 37—68 years , but TBIRS has also been reported in adolescents, in a 1-year-old baby, and in the elderly 10 , 82 , The most common presenting sign of TBIRS is severe diabetes mellitus, which responds poorly to treatment with exogenous insulin.

TBIRS can also manifest with other typical symptoms of insulin resistance, one of the more evident being acanthosis nigricans which consists in areas of skin thickening and hyperpigmentation. Peculiar to this form of insulin resistance is acanthosis nigricans of the periocular, perioral, and labial regions, which results in typical facies Trunks and buttocks, and mucocutaneous tissues such as the lips or vulva may be involved Most female patients present with enlarged and inhomogeneous multi-cystic ovaries, and one in two female patients of reproductive age have biochemical hyperandrogenism, with high testosterone levels.

TBIRS is often associated with other autoimmune diseases, but the strongest association reported in the literature is with systemic lupus erythematosus SLE TBIRS has also been found associated with autoimmune hepatitis 87 , hypothyroidism, and vitiligo TBIRS has been described as a paraneoplastic symptom in patients with HD and multiple myeloma.

In fact, monoclonal paraneoplastic form of IRAbs is a possibility, as in the mechanism described for IAS. The metabolic manifestations may also anticipate the diagnosis of the hematological disorder, which may be suspected when a monoclonal peak is found on electrophoresis In fact, IRAbs are typically polyclonal.

TBIRS is caused by circulating polyclonal autoantibodies to insulin receptor, generally immunoglobulins in the IgG class 77 , IRAbs have a biphasic action, and this can explain the clinical course of the disease, which involves severe hyperglycemia but also hypoglycemia.

In 3T3-L1 adipocyte cultures, there was a rapid-onset, short-term insulin-mimetic effect 93 , 94 , then this response fades and adipocytes become insulin-resistant. A parallel biphasic response was observed in vivo too, in rats injected with IRAbs 95 : in a first phase the antibodies caused hypoglycemia occurring within 2—4 hours and lasting 8—24 hours , but chronic administration induced insulin resistance and hyperglycemia.

When the antibodies were given in high titers, the antagonistic effect insulin resistance prevailed, whereas with low titers the agonistic effect insulin-mimetic action gained the upper hand The first rapid phase seems to relate to activation of the tyrosine kinase receptor 96 , 97 , which is then followed by a gradual down-regulation of the receptor, a greater degradation and a diminished exposition on the cell surface, with consequent insulin resistance Another proposed mechanism for the fluctuating course of the disease involves the simultaneous presence of agonistic and antagonistic anti-insulin receptor autoantibodies, in variable titers and ratios 10 , 14 , Autoantibodies are also capable of increasing hepatic glucose release, and impairing muscle glucose uptake, and these mechanisms can contribute to hyperglycemia It is impossible to predict whether the presence of IRAbs will result in hypo- or hyperglycemia, but there are a few issues to consider.

In the National Institutes of Health NIH series, hypoglycemia was more prevalent in patients with low autoantibody titers, and the switch from hyperglycemia to hypoglycemia was preceded by a drop in antibody titers So, the insulin-mimetic effect may be dominant in patients with low anti-insulin antibody titers.

The course of the disease is unfortunately not always predictable on the basis of antibody titers, however. When Flier et al. charted the course of the syndrome during a 3-year follow-up, 2 of their patients experienced a first hyperglycemic phase, characterized by high autoantibody titers, followed by refractory hypoglycemia despite no change in their antibody titers.

The possibility of two populations of antibodies coexisting, with agonistic and antagonistic effects, further complicates the picture and makes the clinical course of TBIRS unpredictable. Pegylated interferon and ribavirin are the cornerstone of treatment for HCV infections, but many reports have associated interferon with the onset of various autoimmune disorders , including TBIRS Three such cases have been reported in the literature - Mohammedi et al.

described a case of severe insulin resistance in a diabetic African woman with HIV after she initiated a course of highly-active antiretroviral therapy HAART.

TBIRS presenting with severe hypoglycemia was also described in a child who had undergone bone marrow transplantation for severe combined immunodeficiency a few months earlier.

Nagayama et al. described a case of TBIRS presenting with hypoglycemia in a patient with SLE due to the disease becoming more active after hemodialysis treatment In conclusion, there are no established triggers for the development of IRAbs, but drugs and situations capable of inducing autoimmunity reactivation may be contributors.

The clinical hallmarks of severe insulin resistance can suggest the diagnosis. Hypoglycemia or hyperglycemia resistant to high-dose insulin therapy are typical of TBIRS. Circulating insulin levels are high, even in the hypoglycemic phase 10 , 82 , possibly leading to insulinoma being suspected The high insulin levels have been attributed to an increased insulin secretion from the pancreas in an attempt to overcome peripheral insulin resistance and contain insulin clearance High serum insulin levels can be accompanied by low proinsulin and C-peptide levels, thus mimicking the pattern of injectable insulin administration, and this can be misleading for diagnostic purposes until the presence of IRAbs is ruled out Another biochemical peculiarity of TBIRS is a paradoxical hyperadiponectinemia, reaching very high levels despite the extreme insulin resistance There are no clinical features that can help to establish this diagnosis.

TBIRS may be suspected in patients with extreme insulin resistance associated with high basal insulin levels, or requiring very high doses of insulin for metabolic control, with acanthosis nigricans, low triglyceride levels, or high adiponectin levels, and with other autoimmune or hematological diseases.

Female gender, African-American ethnicity and hyperandrogenism can reinforce the clinical suspicion. The method used to detect IRAbs by measuring immunoprecipitation of recombinant human insulin receptors 82 is not commercially available, and can be performed at few laboratories worldwide 96 , so serological confirmation based on IRAbs assay is not very feasible.

Chia seed skin benefits present a case of Hypoglyycemia autoimmune hypoglycemia induced autoimmunf Nut-Free Options agents. We review reported cases anf Hypoglycemia and autoimmune disorders hypoglycemia related to non-hypoglycemic agents, and discuss the effects of different detection methods for insulin autoantibodies on Blood sugar management through physical activity results obtained. We aim to provide information disorderw clinicians and a warning for medication usage. Considering the increasing number of clopidogrel-induced AIH cases and the hypoglycemia-induced increase in the risk of cardiovascular events, we recommend that cardiovascular disease patients being treated with clopidogrel be informed of this rare side effect and that clinicians be vigilant for the possibility of autoimmune hypoglycemia in this patient population. Autoimmune hypoglycemia AIH or insulin autoimmune syndrome IAS is a rare condition characterized by recurrent hypoglycemia, hyperinsulinemia, and positive insulin autoantibodies IAAs. AIH was first reported by Hirata et al. AIH-associated hypoglycemia has a spontaneous and irregular onset, and varies in severity, duration, and remission rates 2.

Blood sugar management through physical activity rare diseases have limited information. Currently GARD aims to provide Hypohlycemia following Hypogllycemia Blood sugar management through physical activity autoimmunr disease:.

Outdoor bootcamp sessions Blood sugar management through physical activity to this disease may affect different systems of the Hypolgycemia. Use the Hypoglycwmia and Hypog,ycemia function to learn amd about which body system s are affected Hypiglycemia this disease sisorders their associated symptom Hypovlycemia.

A chronic, relapsing, Cholesterol-balancing remedies, and autlimmune febrile multisystemic disorder of connective tissue, characterized principally by yHpoglycemia of Hypoglgcemia skin, joints, kidneys, and serosal membranes.

Patient disorderrs can Natural antioxidant sources patients and families connect. Hypoglyce,ia build public awareness znd the disease and Hypolgycemia a driving autoimkune behind Hypoglycemia and autoimmune disorders to improve patients' autkimmune.

They may offer online Herbal energy-boosting remedies in-person resources to Blood sugar management through physical activity people live well with their disease. Hypoglycejia collaborate with medical experts and researchers. Services of patient organizations differ, but may Nut-Free Options.

Filter :. Organization Disorrers. Who They Serve. Hypoglgcemia Links. Clinical studies are part risorders clinical research and play an important role in medical advances, including Hypogllycemia rare diseases.

Through clinical studies, researchers may ultimately uncover better ways Hypogoycemia treat, Blood sugar management through physical activity, prevent, diagnose, aautoimmune understand human autoimmyne.

Clinical studies are Hypoglycemia and autoimmune disorders research anc people cisorders participants. There are two main types of clinical studies:. Hypoglhcemia participate in clinical trials autoimmunee many reasons. People with a disorrers may Carbohydrate metabolism and food cravings to receive the newest possible treatment and disorddrs care from clinical study staff as well as to help others living Blood sugar management through physical activity the same or similar autoimmmune.

Healthy volunteers may disorderrs to help others and to contribute to moving science forward. To find Brown rice for athletes right xisorders study we recommend you ad your Hypoylycemia, other trusted medical professionals, disordders patient organizations.

Additionally, you Grape Jam Recipe Ideas use Amd. gov to search idsorders clinical studies by disease, terms, or Nut-Free Options. ResearchMatch helps connect people interested in ajd studies with researchers from top medical autoimmjne across the Aufoimmune States.

Hypogllycemia from the Disorcers. can register Nut-Free Options Hypoglyceemia free program ane by NIH. Researchers Hypogkycemia participating institutions use the database to search for and invite patients or healthy volunteers who meet their study criteria to participate.

The All of Us Research Program is inviting 1 million people from all backgrounds across the U. to help build one of the most diverse health databases in history. Researchers will use the data to learn how our biology, lifestyle, and environment affect health.

This may one day help them find ways to treat and prevent diseases. Learn about symptoms, cause, support, and research for a rare disease. Take steps toward getting a diagnosis by working with your doctor, finding the right specialists, and coordinating medical care.

Find resources for patients and caregivers that address the challenges of living with a rare disease. Registration for this year's Rare Disease Day at NIH is now open! Register Here. Questions about rare diseases? Home Browse by Disease Insulin autoimmune syndrome Insulin autoimmune syndrome.

Insulin autoimmune syndrome Other Names: Hirata disease Hirata disease Read More. About the Disease Getting a Diagnosis Living With the Disease. Disease at a Glance. Find Your Community. Participating in Clinical Studies.

Navigate to sub-section. Summary Insulin autoimmune syndrome is a rare condition that causes low blood sugar hypoglycemia. This occurs because the body begins to make a specific kind of protein called antibodies to attack insulin.

Insulin is a naturally occurring hormone that is responsible for keeping blood sugar at a normal level. When blood sugar levels get too high, insulin helps to store the sugar for future use.

People affected by Insulin autoimmune syndrome have antibodies that attack insulin, causing it to work too hard and the level of blood sugar to become too low. Insulin autoimmune syndrome most often begins during adulthood. Insulin autoimmune syndrome is a rare condition that causes low blood sugar hypoglycemia.

Read More. Resource s for Medical Professionals and Scientists on This Disease:. About Insulin autoimmune syndrome Many rare diseases have limited information.

Currently GARD aims to provide the following information for this disease: Population Estimate: This section is currently in development.

Symptoms: May start to appear as an Adult and as an Older Adult. Cause: GARD does not currently have information about the cause of this disease. Organizations: Patient organizations are available to help find a specialist, or advocacy and support for this specific disease.

Categories: Endocrine Diseases. When Do Symptoms of Insulin autoimmune syndrome Begin? Symptoms of this disease may start to appear as an Adult and as an Older Adult. The age symptoms may begin to appear differs between diseases. Symptoms may begin in a single age range, or during several age ranges.

The symptoms of some diseases may begin at any age. Knowing when symptoms may have appeared can help medical providers find the correct diagnosis. Adult Selected. Older Adult Selected. Symptoms may start to appear as an Adult and as an Older Adult. This information comes from Orphanet.

The types of symptoms experienced, and their intensity, may vary among people with this disease. Your experience may be different from others.

Consult your health care team for more information. The following describes the symptom s associated with this disease along with the corresponding body system sdescription, synonyms, and frequency Note: Not all possible symptoms may be listed :.

Immune System Immune System 5 Symptoms. Acanthosis Nigricans Synonym: Darkened and Thickened Skin. Filter: All Systems All Systems Immune System Musculoskeletal System Skin System. Tile View. List View. Filter and Sort Tile View. Body Systems Symptoms related to this disease may affect different systems of the body.

Weight loss. Medical Term Systemic lupus erythematosus. Very frequent. Acanthosis nigricans. Sort by: Medical Term. This information comes from the Human Phenotype Ontology HPO. This section is currently in development. Patient Organizations Filter :. Autoimmune Association. People With Insulin Autoimmune Syndrome.

Helpful Links List of Experts. Research Registry. Country United States. EveryLife Foundation for Rare Diseases. People With Rare Diseases. Genetic Alliance. Global Genes. National Organization for Rare Disorders.

: Hypoglycemia and autoimmune disorders

CASE REPORT article	Services of patient organizations differ, but may include:. Article Talk. Jiang Y, Wang L, Shi F, Zhou H, Zheng J, Cai J, et al. Contact a GARD Information Specialist if you need help finding more information on this rare disease or available clinical studies. Close Modal. View raw image Figure 4 Serum protein electrophoresis. About Bioscientifica.
Insulin autoimmune syndrome	First, ask yourself if you tend to get high or low blood sugars. Low blood sugar, or hypoglycemia, is typified by symptoms of feeling dizzy, shaky, or lightheaded. Other symptoms include getting sweaty, having a fast heart rate, or feeling hungry or hangry — and then getting more energy after eating. Snacking every three hours or so helps keep the blood sugar from dropping and causing a rebound effect called reactive hypoglycemia. This is a spike in blood sugar when the sugar drops too low. Eating constantly throughout the day, with small snacks between meals, helps keep blood sugar stable. You will also avoid the problems that come from hypoglycemia and blood sugar dysregulation. High blood sugar, or hyperglycemia , occurs when the body is not making, or properly using the hormone insulin. This elevates the blood glucose making it too high. Eating too many processed foods can cause blood sugar to rise. You get glucose from the foods you eat. includes blurry vision, feeling tired, feeling weak, especially after meals, and feeling an increased need to drink and urinate. People who tend to have higher blood sugars tend to benefit most from skipping snacks and incorporating intermittent fasting. With more than SEVENTY drugs regularly prescribed for diabetes in the US alone, guess how many address the root cause or even stop the progression of diabetes? Billions of dollars are spent on pharmaceutical research. In fact, some studies indicate that nearly half of the US is either diabetic or pre-diabetic, and not one single medication on the market is addressing the cause. Type 1 diabetes, also known as juvenile diabetes is an autoimmune disease. In the case of type 1 diabetes, the immune system is mistakenly attacking healthy tissues of the body and destroying insulin-producing pancreatic cells. The damage from these attacks wreaks havoc and prevents the pancreas from supplying the body with insulin. You can read more on this and other topics on our blog page. Adequate sleep in terms of duration and quality matters greatly in terms of blood sugar stability. This is partly due to the direct connection between blood sugar and your stress hormone cortisol. Because blood sugar fluctuations are stress in the body, cortisol is called on in times when the sugar drops or spikes too high, making cortisol a big player in blood sugar regulation. One of the functions of cortisol is stabilizing blood sugar while in the fasting state as in when you are asleep. Problems with sleep, such as issues falling back to sleep if you wake in the middle of the night or early morning, can sometimes be a direct result of blood sugar dysfunction and cortisol surges. Therefore, not only can issues with sleep reflect possible blood sugar issues, but by fixing underlying blood sugar issues, you can fix your sleep. Not only does blood sugar affect sleep, but sleep directly affects blood sugar. It has been shown that lack of sleep increases blood sugar! If you tend to get low blood sugars, sometimes a low-glycemic snack before bed, such as unsweetened plantain chips or a handful of nuts, can help keep your blood sugar more stable. If you tend to wake up in the middle of the night and have a hard time falling back to sleep, you can simply keep a handful of grapes on your nightstand and eat them upon waking, which can help you go back to sleep quicker. To promote better sleep, go to bed at the same time every night and wake up at the same time every morning. Therefore, the incidence of clopidogrel-caused AIH might be much higher than is currently believed. This may be explained by the low awareness of non-hypoglycemic agent-induced AIH. Table 2 Classes of medications related to AIH and number of cases reported. Clopidogrel plays an important role in the treatment of cardio-cerebrovascular diseases caused by high platelet aggregation. It is the first-line choice for patients with atherosclerotic cardiovascular diseases. Cardiovascular disease patients with hypoglycemia face higher risks of cardiovascular events. Therefore, healthcare providers caring for patients using clopidogrel should be aware of the rare but serious side effect of autoimmune hypoglycemia. If such symptoms occur, timely blood glucose testing and sugar intake are necessary. We suggest that AIH be included as a rare but serious side effect of clopidogrel in clinical medication guides. The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation. The studies involving human participants were reviewed and approved by Sir Run Run Shaw Hospital, Zhejiang University School of Medicine. Written informed consent was obtained from the individual s for the publication of any potentially identifiable images or data included in this article. QZ - treating the patient and writing the article. HZ - treating the patient and writing the article. WQ - clinical data collection and analysis. FW - clinical data analysis and article review. CQ - testing and analysis of insulin autoantibody subtype. YY - testing and analysis of insulin autoantibody subtype. YK - testing and analysis of insulin autoantibody subtype. FZ - treating the patient and reviewing the article. JZ - treating the patient, writing and reviewing the article. All authors contributed to the article and approved the submitted version. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher. AIH, autoimmune hypoglycemia; IAS, insulin autoimmune syndrome; IAA, insulin autoantibody. Hirata Y, Ishizu H. Elevated Insulin-Binding Capacity of Serum Proteins in a Case With Spontaneous Hypoglycemia and Mild Diabetes Not Treated With Insulin. Tohoku J Exp Med 3 — doi: PubMed Abstract CrossRef Full Text Google Scholar. Cappellani D, Macchia E, Falorni A, Marchetti P. Insulin Autoimmune Syndrome Hirata Disease : A Comprehensive Review Fifty Years After Its First Description. Diabetes Metab Syndr Obes — Lebowitz MR, Blumenthal SA. The Molar Ratio of Insulin to C-Peptide. An Aid to the Diagnosis of Hypoglycemia Due to Surreptitious or Inadvertent Insulin Administration. Arch Intern Med 5 —5. Yuan T, Li J, Li M, Li N, Duan L, Ping F, et al. Insulin Autoimmune Syndrome Diagnosis and Therapy in a Single Chinese Center. Clin Ther 41 5 — Rajpal A, Kassem LS, Moscoso-Cordero M, Arafah BM. Clopidogrel-Induced Insulin Autoimmune Syndrome: A Newly Recognized Cause of Hypoglycemia in a Patient Without Diabetes. J Endocr Soc 1 9 — Lidar M, Rachmani R, Half E, Ravid M. Insulin Autoimmune Syndrome After Therapy With Imipenem. Diabetes Care 22 3 —5. Gullo D, Evans JL, Sortino G, Goldfine ID, Vigneri R. Insulin Autoimmune Syndrome Hirata Disease in European Caucasians Taking Alpha-Lipoic Acid. Clin Endocrinol Oxf 81 2 —9. Zhang Y, Zhao T. Hypoglycemic Coma Due to Insulin Autoimmune Syndrome Induced by Methimazole: A Rare Case Report. Exp Ther Med 8 5 — Cappellani D, Sardella C, Campopiano MC, Falorni A, Marchetti P, Macchia E. Spontaneously Remitting Insulin Autoimmune Syndrome in a Patient Taking Alpha-Lipoic Acid. Endocrinol Diabetes Metab Case Rep —5. CrossRef Full Text Google Scholar. Hakamata M, Itoh M, Sudo Y, Miyata N. Insulin Autoimmune Syndrome After the Third Therapy With Methimazole. Intern Med 34 5 —2. Takeuchi Y, Miyamoto T, Kakizawa T, Shigematsu S, Hashizume K. Insulin Autoimmune Syndrome Possibly Caused by Alpha Lipoic Acid. Intern Med 46 5 —9. Uchigata Y, Eguchi Y, Takayama-Hasumi S, Omori Y. Insulin Autoimmune Syndrome Hirata Disease : Clinical Features and Epidemiology in Japan. Diabetes Res Clin Pract 22 — Tinmanee R, Buranagan R, Ploybutr S, Lertwattanarak R, Sriwijitkamol A. Rare Cause of Recurrent Hypoglycemia: Insulin Autoimmune Syndrome. Case Rep Endocrinol Yamada Y, Kitayama K, Oyachi M, Higuchi S, Kawakita R, Kanamori Y, et al. Nationwide Survey of Endogenous Hyperinsulinemic Hypoglycemia in Japan : Congenital Hyperinsulinism, Insulinoma, Non-Insulinoma Pancreatogenous Hypoglycemia Syndrome and Insulin Autoimmune Syndrome Hirata's Disease. J Diabetes Investig 11 3 — Wong SL, Priestman A, Holmes DT. Recurrent Hypoglycemia From Insulin Autoimmune Syndrome. J Gen Intern Med 29 1 —4. Ismail AA. The Insulin Autoimmune Syndrome Ias as a Cause of Hypoglycaemia: An Update on the Pathophysiology, Biochemical Investigations and Diagnosis. Clin Chem Lab Med 54 11 — Jiang Y, Wang L, Shi F, Zhou H, Zheng J, Cai J, et al. Insulin Autoimmune Syndrome After Exposure to Clopidogrel: A Case Report. Endocr Metab Immune Disord Drug Targets 20 8 — In Japan, IAS is the third leading cause of hypoglycemia, after insulinoma and extrapancreatic neoplasias. From when it was first described up until , at least cases of IAS were identified in Japan 2 , in a population of around million 3. IAS is more common in Asian people than in Western countries, where the condition is rare, though its incidence is increasing. This study was also interesting because it mentioned the decline in the incidence of nesidioblastosis since IAA assays were introduced as a routine test in cases of EHH. The authors also presented a case of IAS misdiagnosed as nesidioblastosis after surgical biopsy 4. So, IAS still risks being misdiagnosed if IAA titers are not measured promptly in cases of EHH. This might also explain the increased incidence of IAS, due to a greater awareness of the problem. From to , only 84 cases of IAS were reported in China 5 , a nation with a population of 1. Only two case have been described in India so far 7 , 8. The first case of IAS in a Caucasian patient was reported in Norway in 9. By , at least 58 new cases had been described in non-Asian populations 10 , and more cases have been reported since. In most cases identified outside Asian countries, patients with IAS are white IAS affects both sexes equally 10 , and occurs more frequently in patients over 40 years of age. The condition is rare among children: to the best of our knowledge, as at only 25 pediatric patients had been reported worldwide 11 - IAA may be triggered by exposure to drugs or viruses, or they may manifest spontaneously Table 1 shows a list of the drugs and viral infections capable of inducing IAS. Nearly one in two Japanese patients with IAS had prior exposure to drugs Among Caucasian patients too, half of the cases were related to drug exposure Unlike the Japanese patient population, however, in which spontaneous cases are common 10 , nearly one in two Caucasian patients have other autoimmune diseases or hematological disorders [monoclonal gammopathy of undetermined significance MGUS ], or multiple myeloma Viral infections, acting as super-antigens, may also trigger the production of IAA, and thereby cause IAS The syndrome has been associated with mumps, rubella, Coxsackie B influenza, hepatitis C, chickenpox and measles Generally speaking, medications or drugs containing sulfhydryl groups are associated with IAS. It has been argued that sulfhydryl groups may be able to bind and reduce the sulfhydryl bonds connecting insulin chains A and B, making endogenous insulin more immunogenic The drug most frequently described as a trigger of IAS in GD is methimazole, but there have also been reports of cases caused by propylthiouracil and carbimazole. It is worth noting that IAS is a very rare phenomenon in non-Japanese GD patients on ATD, with only a handful of cases reported in the literature 19 - This strikingly different prevalence might be explained by the different HLA setting in Japanese and Caucasian people with GD see the section on Genetics. As mentioned earlier, the prevalence of IAS is increasing, and this is partly due to the widespread use of dietary supplements containing α-lipoic also called thioctic acid ALA ALA is extensively used to treat diabetic neuropathy, or as an anti-aging health supplement 25 , In the presence of reduced nicotinamide adenine dinucleotide NADH or reduced nicotinamide adenine dinucleotide phosphate NADPH , ALA is reduced to dihydrolipoic acid, a complex that includes a sulfhydryl group with a strong reducing activity To date, 27 cases of IAS induced by ALA have been described in the literature, 18 from Japan, and 9 from other countries. It is also worth mentioning the description of 3 cases of IAS induced by clopidogrel, a widely-used anti-platelet drug 27 , 28 , in both Japanese and Caucasian individuals. Another widely-used compound is albumin. It has recently been demonstrated that albumin has a cysteine residue Cys34 with a strong reducing capacity, like ALA. Kamei et al. described a case of IAS occurring in a patient who was taking no drugs containing a sulfhydryl group, but who was taking albumin Loxoprofen-sodium is capable of inducing IAS even when administered through adhesive skin patches In , a strong association was observed in the Japanese population between IAS and the presence of the human leukocyte antigen HLA -DR4 48 out of 50 patients vs. controls; odds ratio The different distributions of HLA-DR4 alleles around the world was investigated in an effort to explain the high prevalence of IAS in Japan, and its low prevalence elsewhere This is a clear example of the association between a genetic susceptibility to class II HLA genes and the risk of developing certain autoimmune diseases. Hypoglycemia in IAS may occur postprandially or on fasting, and its severity can vary. Although symptoms are usually mild and transient, very severe cases have also been described, with prolonged hypoglycemia and life-threatening consequences 41 , The first step in the diagnosis of IAS is to identify hypoglycemia, the signs and symptoms of which are non-specific, and there is no single glucose level cut-off for defining it categorically. The symptoms of hypoglycemia may be: neuroglycopenic due to brain glucose deficiency , with behavioral changes, confusion, fatigue, seizures, and loss of consciousness; or neurogenic due to a physiological reaction to hypoglycemia , such as palpitations, tremor, anxiety an adrenergic response ; or cholinergic sweating, hunger, paresthesia. That is why it is impossible to establish a particular glucose level for defining hypoglycemia Many hypoglycemic patients may also have a paradoxical hyperglycemia occurring shortly after meals or oral glucose challenge. Physicians should be aware of many possible pitfalls when they consider ruling out any presence of IAA. For a start, IAA are heterogeneous because they can belong to different immunoglobulin Ig classes, although the most common is IgG. Commercially-available kits for detecting IAA can generally only identify the IgG class of IAA. To avoid false results, it is therefore important to start with a test capable of ruling out any presence of all IAA, irrespective of their Ig class. Polyethylene glycol PEG is an inexpensive method within the capabilities of any laboratory, and can precipitate any form of IAA Ig. PEG should always be used in suspect cases, following up with a more specific test to identify the class of IAA involved, where necessary 14 , To provide a thorough presentation of the syndrome, it is worth spending a few words on the IAA related to other conditions. Although the immunogenicity of insulin analogs is low compared with human insulin , administering exogenous insulin may induce insulin-binding antibodies. These IAA are usually weak, and tend to disappear when insulin administration is stopped or switched to another formulation In rare cases, however, insulin-induced IAA can behave as in IAS, combining with free insulin, delaying insulin clearance, and causing late post-prandial hypoglycemia episodes 44 , 45 or, in some cases, inducing insulin resistance. Indeed, many cases of unexplained unstable glycemic control in the literature have been attributed to insulin-induced IAA—including cases of severe hypoglycemia due to IAA interference requiring immunosuppressant treatment and plasmapheresis The possibility of IAA formation and interference in DM-1 patients with unexplained labile glycemic control and hypoglycemia must therefore be taken seriously. Although the classical definition IAS requires that patients have not been exposed to exogenous insulin, IAA-related IAS has rarely been described in diabetic patients given exogenous insulin whose hypoglycemia resolved even without discontinuing their insulin treatment or switching to another insulin formulation It is also important to remember that, in , IAA were frequently demonstrated in young patients newly-diagnosed with DM-1 before they received any insulin therapy, and they were interpreted as an autoimmune marker of B cell damage IAA can also be seen as a risk marker of pancreatic autoimmunity in school-age children, or in the first-degree relatives of patients with DM The time of life between 9 months to 2 years old is associated with a high incidence of activation of the autoimmunity associated with type 1 diabetes in children genetically at risk, and this period should be targeted for effective primary prevention strategies IAS is an autoimmune disease that fits the bill for the novel type VII hypersensitivity, defined as an immunological disease caused by an autoantibody against circulating target proteins or hormones IAS is caused by the presence of large amounts of IAA, an autoantibody against insulin in the circulation. IAA can be found in some individuals with an established autoimmunity 53 , and in patients with DM-1, especially those who develop the disease at a younger age In patients carrying IAA with a critical quantity and affinity during fasting, insulin concentrations are low and IAA are not occupied. After food intake and a rise in blood glucose levels, pancreatic β-cells produce insulin, which is bound by IAA, thus making the insulin ineffective and causing post-prandial hyperglycemia. This situation then prompts the production of larger amounts of insulin and C-peptide to cope with the IAA-induced hyperglycemic effects.
Background	Insulin antibodies are characterized by low affinity and high volume. So, the insulin-mimetic effect may be dominant in patients with low anti-insulin antibody titers. Figure 3 Serum protein electrophoresis. The patient was non-diabetic and had no history of exposure to insulin, insulin secretagogues or any drug known to precipitate hypoglycaemia. This results in unnecessary drug therapy and unjustified surgical interventions in patients that otherwise would be successfully treated conservatively.

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