Hyperinsulinemia

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Hyperinsulinemia
Other namesHyperinsulinaemia
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Insulin binding to its receptor
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Hyperinsulinemia is a condition in which there are excess levels of insulin circulating in the blood relative to the level of glucose. While it is often mistaken for diabetes or hyperglycaemia, hyperinsulinemia can result from a variety of metabolic diseases and conditions, as well as non-nutritive sugars in the diet. [1] [ better source needed ] While hyperinsulinemia is often seen in people with early stage type 2 diabetes mellitus, it is not the cause of the condition and is only one symptom of the disease [ citation needed ] (for opposing view see review in [2] ). Type 1 diabetes only occurs when pancreatic beta-cell function is impaired. Hyperinsulinemia can be seen in a variety of conditions including diabetes mellitus type 2, in neonates and in drug-induced hyperinsulinemia. It can also occur in congenital hyperinsulinism, including nesidioblastosis.

Contents

Hyperinsulinemia is associated with hypertension, obesity, dyslipidemia, insulin resistance, and glucose intolerance. [3] These conditions are collectively known as metabolic syndrome. [4] This close association between hyperinsulinemia and conditions of metabolic syndrome suggest related or common mechanisms of pathogenicity. [3] Hyperinsulinemia has been shown to "play a role in obese hypertension by increasing renal sodium retention". [3]

In type 2 diabetes, the cells of the body become resistant to the effects of insulin as the receptors which bind to the hormone become less sensitive to insulin concentrations resulting in hyperinsulinemia and disturbances in insulin release. [5] With a reduced response to insulin, the beta cells of the pancreas secrete increasing amounts of insulin in response to the continued high blood glucose levels resulting in hyperinsulinemia. In insulin resistant tissues, a threshold concentration of insulin is reached causing the cells to uptake glucose and therefore decreases blood glucose levels. Studies have shown that the high levels of insulin resulting from insulin resistance might enhance insulin resistance. [5]

Studies on mice with genetically reduced circulating insulin suggest that hyperinsulinemia plays a causal role in high fat diet-induced obesity. In this study, mice with reduced insulin levels expended more energy and had fat cells that were reprogrammed to burn some energy as heat. [6]

Hyperinsulinemia in neonates can be the result of a variety of environmental and genetic factors. If the mother of the infant is a diabetic and is not able to properly control her blood glucose levels, the hyperglycemic maternal blood can create a hyperglycemic environment in the fetus. To compensate for the increased blood glucose levels, fetal pancreatic beta cells can undergo hyperplasia. The rapid division of beta cells results in increased levels of insulin being secreted to compensate for the high blood glucose levels. Following birth, the hyperglycemic maternal blood is no longer accessible to the neonate resulting in a rapid drop in the newborn's blood glucose levels. As insulin levels are still elevated this may result in hypoglycemia. To treat the condition, high concentration doses of glucose are given to the neonate as required maintaining normal blood glucose levels. The hyperinsulinemia condition subsides after one to two days. [7]

Symptoms and signs

A large abdomen is a strong indicator of Hyperinsulinemia, so measure waist to hip ratio. But the best way to know if you have hyperinsulinemia is to get insulin levels checked. It is important to note that in some people Insulin can be elevated in the presence of normal glucose for 10-20 years, so it is best not to rely on glucose levels without also measuring insulin [ citation needed ]

Some patients may experience a variety of symptoms when hypoglycemia is present, including: [8]

If a person experiences any of these symptoms, a visit to a qualified medical practitioner is advised, and diagnostic blood testing, such as Fasting Insulin Levels, may be required.[ citation needed ]

Causes

Possible causes include:[ citation needed ]

Often, individuals get metabolically (internally) sick before showing signs of obesity. But visceral obesity can go undetected, and is extremely dangerous. Lifestyle choices including diet, exercise, and sleep deprivation play the largest role in Hyperinsulinemia & insulin resistance.[ citation needed ]

Belly fat is a strong predictor of high insulin levels. Obesity is characterized by an excess of adipose tissue – insulin increases the synthesis of fatty acids from glucose, facilitates the entry of glucose into adipocytes and inhibits breakdown of fat in adipocytes. [11]

On the other hand, adipose tissue is known to secrete various metabolites, hormones and cytokines that may play a role in causing hyperinsulinemia. [12] Specifically cytokines secreted by adipose tissue directly affect the insulin signalling cascade, and thus insulin secretion. [13] Adiponectins are cytokines that are inversely related to percent body fat; that is people with a low body fat will have higher concentrations of adiponectins where as people with high body fat will have lower concentrations of adiponectins. In 2011, it was reported that hyperinsulinemia is strongly associated with low adiponectin concentrations in obese people, though whether low adiponectin has a causal role in hyperinsulinemia remains to be established. [13]

Diagnosis

Fasting Insulin levels in blood may be measured as this can be elevated in the presence of normal glucose. Diagnosis is often made by checking normal levels of glucose that exceed 1.7 mmol/L (30 mg/dL) when 1 mg of glucagon is administered IM or IV. [16] In addition, urine samples or blood samples are also used to check levels of ketones and low free fatty acids. [17]

After diagnosis, most people are required to continue regular check ups for evaluations. [17]

Differential diagnosis

Treatment

Treatment is typically achieved via diet and exercise, although metformin may be used to reduce insulin levels in some patients (typically where obesity is present). A referral to a dietician is beneficial. Another method used to lower excessively high insulin levels is cinnamon, specifically Ceylon cinnamon, [19] as was demonstrated when supplemented in clinical human trials. [20]

A healthy diet that is low in simple sugars and processed carbohydrates, and high in fiber, and vegetable protein is often recommended. This includes replacing white bread with whole-grain bread, reducing intake of foods composed primarily of starch such as potatoes, and increasing intake of legumes and green vegetables, particularly soy. [21]

Regular monitoring of weight, blood sugar, and insulin are advised, as hyperinsulinemia may develop into diabetes mellitus type 2. [22]

It has been shown in many studies that physical exercise improves insulin sensitivity. [23] The mechanism of exercise on improving insulin sensitivity is not well understood however it is thought that exercise causes the glucose receptor GLUT4 to translocate to the membrane. [24] As more GLUT4 receptors are present on the membrane more glucose is taken up into cells decreasing blood glucose levels which then causes decreased insulin secretion and some alleviation of hyperinsulinemia. [23] Another proposed mechanism of improved insulin sensitivity by exercise is through AMPK activity. [23] The beneficial effect of exercise on hyperinsulinemia was shown in a study in 2009, where they found that improving fitness through exercise significantly decreases blood insulin concentrations. [23] Moreover, a diet that consists of high amounts of carbs have been linked to weight gain and obesity in rodents. Although this has not been tested in humans, it is assumed that it could aid with the prevention of weight gain in humans, and possibly obesity. [25] Medications have also been studied to treat hyperinsulinemia, although these might have some side effects, these could be used as an alternative. [26]

See also

Related Research Articles

<span class="mw-page-title-main">Metabolic syndrome</span> Medical condition

Metabolic syndrome is a clustering of at least three of the following five medical conditions: abdominal obesity, high blood pressure, high blood sugar, high serum triglycerides, and low serum high-density lipoprotein (HDL).

Insulin resistance (IR) is a pathological condition in which cells in insulin-sensitive tissues in the body fail to respond normally to the hormone insulin or downregulate insulin receptors in response to hyperinsulinemia.

<span class="mw-page-title-main">Abdominal obesity</span> Excess fat around the stomach and abdomen

Abdominal obesity, also known as central obesity and truncal obesity, is the human condition of an excessive concentration of visceral fat around the stomach and abdomen to such an extent that it is likely to harm its bearer's health. Abdominal obesity has been strongly linked to cardiovascular disease, Alzheimer's disease, and other metabolic and vascular diseases.

<span class="mw-page-title-main">Hyperglycemia</span> Too much blood sugar, usually because of diabetes

Hyperglycemia or Hyperglycaemia is a condition in which an excessive amount of glucose (glucotoxicity) circulates in the blood plasma. This is generally a blood sugar level higher than 11.1 mmol/L (200 mg/dL), but symptoms may not start to become noticeable until even higher values such as 13.9–16.7 mmol/L (~250–300 mg/dL). A subject with a consistent fasting blood glucose range between ~5.6 and ~7 mmol/L is considered slightly hyperglycemic, and above 7 mmol/L is generally held to have diabetes. For diabetics, glucose levels that are considered to be too hyperglycemic can vary from person to person, mainly due to the person's renal threshold of glucose and overall glucose tolerance. On average, however, chronic levels above 10–12 mmol/L (180–216 mg/dL) can produce noticeable organ damage over time.

<span class="mw-page-title-main">Type 2 diabetes</span> Form of diabetes mellitus

Type 2 diabetes (T2D), formerly known as adult-onset diabetes, is a form of diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. Common symptoms include increased thirst, frequent urination, fatigue and unexplained weight loss. Symptoms may also include increased hunger, having a sensation of pins and needles, and sores (wounds) that do not heal. Often symptoms develop slowly. Long-term complications from high blood sugar include heart disease, stroke, diabetic retinopathy, which can result in blindness, kidney failure, and poor blood flow in the lower-limbs, which may lead to amputations. The sudden onset of hyperosmolar hyperglycemic state may occur; however, ketoacidosis is uncommon.

<span class="mw-page-title-main">Adipose tissue</span> Loose connective tissue composed mostly by adipocytes

Adipose tissue is a loose connective tissue composed mostly of adipocytes. It also contains the stromal vascular fraction (SVF) of cells including preadipocytes, fibroblasts, vascular endothelial cells and a variety of immune cells such as adipose tissue macrophages. Its main role is to store energy in the form of lipids, although it also cushions and insulates the body.

<span class="mw-page-title-main">Adipocyte</span> Cells that primarily compose adipose tissue, specialized in storing energy as fat

Adipocytes, also known as lipocytes and fat cells, are the cells that primarily compose adipose tissue, specialized in storing energy as fat. Adipocytes are derived from mesenchymal stem cells which give rise to adipocytes through adipogenesis. In cell culture, adipocyte progenitors can also form osteoblasts, myocytes and other cell types.

<span class="mw-page-title-main">Gestational diabetes</span> Medical condition

Gestational diabetes is a condition in which a person without diabetes develops high blood sugar levels during pregnancy. Gestational diabetes generally results in few symptoms; however, it increases the risk of pre-eclampsia, depression, and of needing a Caesarean section. Babies born to individuals with poorly treated gestational diabetes are at increased risk of macrosomia, of having hypoglycemia after birth, and of jaundice. If untreated, diabetes can also result in stillbirth. Long term, children are at higher risk of being overweight and of developing type 2 diabetes.

<span class="mw-page-title-main">Adiponectin</span> Mammalian protein found in Homo sapiens

Adiponectin is a protein hormone and adipokine, which is involved in regulating glucose levels and fatty acid breakdown. In humans, it is encoded by the ADIPOQ gene and is produced primarily in adipose tissue, but also in muscle and even in the brain.

<span class="mw-page-title-main">Resistin</span> Mammalian protein found in Homo sapiens

Resistin also known as adipose tissue-specific secretory factor (ADSF) or C/EBP-epsilon-regulated myeloid-specific secreted cysteine-rich protein (XCP1) is a cysteine-rich peptide hormone derived from adipose tissue that in humans is encoded by the RETN gene.

The term diabetes includes several different metabolic disorders that all, if left untreated, result in abnormally high concentrations of a sugar called glucose in the blood. Diabetes mellitus type 1 results when the pancreas no longer produces significant amounts of the hormone insulin, usually owing to the autoimmune destruction of the insulin-producing beta cells of the pancreas. Diabetes mellitus type 2, in contrast, is now thought to result from autoimmune attacks on the pancreas and/or insulin resistance. The pancreas of a person with type 2 diabetes may be producing normal or even abnormally large amounts of insulin. Other forms of diabetes mellitus, such as the various forms of maturity-onset diabetes of the young, may represent some combination of insufficient insulin production and insulin resistance. Some degree of insulin resistance may also be present in a person with type 1 diabetes.

Glucose transporter type 4 (GLUT4), also known as solute carrier family 2, facilitated glucose transporter member 4, is a protein encoded, in humans, by the SLC2A4 gene. GLUT4 is the insulin-regulated glucose transporter found primarily in adipose tissues and striated muscle. The first evidence for this distinct glucose transport protein was provided by David James in 1988. The gene that encodes GLUT4 was cloned and mapped in 1989.

<span class="mw-page-title-main">Blood sugar regulation</span> Hormones regulating blood sugar levels

Blood sugar regulation is the process by which the levels of blood sugar, the common name for glucose dissolved in blood plasma, are maintained by the body within a narrow range.

<span class="mw-page-title-main">Equine metabolic syndrome</span> Endocrinopathy affecting horses and ponies

Equine metabolic syndrome (EMS) is an endocrinopathy affecting horses and ponies. It is of primary concern due to its link to obesity, insulin dysregulation, and subsequent laminitis. There are some similarities in clinical signs between EMS and pituitary pars intermedia dysfunction, also known as PPID or Cushing's disease, and some equines may develop both, but they are not the same condition, having different causes and different treatment.

<span class="mw-page-title-main">Prediabetes</span> Predisease state of hyperglycemia with high risk for diabetes

Prediabetes is a component of metabolic syndrome and is characterized by elevated blood sugar levels that fall below the threshold to diagnose diabetes mellitus. It usually does not cause symptoms but people with prediabetes often have obesity, dyslipidemia with high triglycerides and/or low HDL cholesterol, and hypertension. It is also associated with increased risk for cardiovascular disease (CVD). Prediabetes is more accurately considered an early stage of diabetes as health complications associated with type 2 diabetes often occur before the diagnosis of diabetes.

A number of lifestyle factors are known to be important to the development of type 2 diabetes including: obesity, physical activity, diet, stress, and urbanization. Excess body fat underlies 64% of cases of diabetes in men and 77% of cases in women. A number of dietary factors such as sugar sweetened drinks and the type of fat in the diet appear to play a role.

In recent years it has become apparent that the environment and underlying mechanisms affect gene expression and the genome outside of the central dogma of biology. It has been found that many epigenetic mechanisms are involved in the regulation and expression of genes such as DNA methylation and chromatin remodeling. These epigenetic mechanisms are believed to be a contributing factor to pathological diseases such as type 2 diabetes. An understanding of the epigenome of diabetes patients may help to elucidate otherwise hidden causes of this disease.

<span class="mw-page-title-main">Diabetes</span> Group of endocrine diseases characterized by high blood sugar levels

Diabetes mellitus, often known simply as diabetes, is a group of common endocrine diseases characterized by sustained high blood sugar levels. Diabetes is due to either the pancreas not producing enough insulin, or the cells of the body becoming unresponsive to the hormone's effects. Classic symptoms include thirst, polyuria, weight loss, and blurred vision. If left untreated, the disease can lead to various health complications, including disorders of the cardiovascular system, eye, kidney, and nerves. Diabetes accounts for approximately 4.2 million deaths every year, with an estimated 1.5 million caused by either untreated or poorly treated diabetes.

<span class="mw-page-title-main">Disposition index</span>

The Disposition index (DI) is a measure for the loop gain of the insulin-glucose feedback control system. It is defined as the product of insulin sensitivity times the amount of insulin secreted in response to blood glucose levels. "Metabolically healthy" Insulin resistant individuals can maintain normal responses to blood glucose due to the fact that higher levels of insulin are secreted as long as the beta cells of the pancreas are able to increase their output of insulin to compensate for the insulin resistance. But the ratio of the incremental increase in plasma insulin associated with an incremental increase in plasma glucose provides a better measure of beta cell function than the plasma insulin response to a glucose challenge. Loss of function of the beta cells, reducing their capacity to compensate for insulin resistance, results in a lower disposition index.

Diabetes mellitus (DM) is a type of metabolic disease characterized by hyperglycemia. It is caused by either defected insulin secretion or damaged biological function, or both. The high-level blood glucose for a long time will lead to dysfunction of a variety of tissues.

References

  1. ↑ Ballantyne, Sarah, "Is It Paleo? Splenda, Erythritol, Stevia, and Other Low-Calorie Sweeteners", 03 Jan 2015, https://www.thepaleomom.com/paleo-splenda-erythritol-stevia-low-calorie-sweeteners/ (last accessed 02 Sept 2020).
  2. ↑ Michael H. Shanik, Yuping Xu, Jan Škrha, Rachel Dankner, Yehiel Zick, Jesse Roth; Insulin Resistance and Hyperinsulinemia: Is hyperinsulinemia the cart or the horse?. Diabetes Care 1 February 2008; 31 (Supplement_2): S262–S268. https://doi.org/10.2337/dc08-s264
  3. 1 2 3 Modan, Michaela; Halkin H; Almog S; Lusky A; Eshkol A; Shefi M; Shitrit A; Fuchs Z (March 1985). "Hyperinsulinemia: A link between hypertension obesity and glucose intolerance". J. Clin. Invest. 75 (3): 809–17. doi:10.1172/JCI111776. PMC   423608 . PMID   3884667.
  4. ↑ Danker, Rache; Chetrit A; Shanik MH; Raz I; Roth J (August 2009). "Basal-stat hyperinsulinemia in healthy normoglycemic adults is predictive of type 2 diabetes over a 24-year follow-up". Diabetes Care. 32 (8): 1464–66. doi:10.2337/dc09-0153. PMC   2713622 . PMID   19435961.
  5. 1 2 Shanik, M.H.; Yuping, X.; Skrha, J.; Danker, R.; Zick, Y.; Roth, J. (2008). "Insulin Resistance and Hyperinsulinemia". Diabetes Care. 31 (2): S262–68. doi: 10.2337/dc08-s264 . PMID   18227495.
  6. ↑ Arya E. Mehran; Nicole M. Templeman; G. Stefano Brigidi; Gareth E. Lim; Kwan-Yi Chu; Xiaoke Hu; Jose Diego Botezelli; Ali Asadi; Bradford G. Hoffman; Timothy J. Kieffer; Shernaz X. Bamji; Susanne M. Clee; James D. Johnson (6 Dec 2012). "Hyperinsulinemia Drives Diet-Induced Obesity Independently of Brain Insulin Production". Cell Metabolism. 16 (5): 723–37. doi: 10.1016/j.cmet.2012.10.019 . PMID   23217255.
  7. ↑ Ferry, R.J. (2010). Hyperinsulinism "Medscape".
  8. ↑ "Hyperinsulinemia means that the amount of insulin in the blood is higher than considered normal amongst non-diabetics". January 15, 2019.
  9. ↑ Stout RW (1996). "Hyperinsulinemia and atherosclerosis". Diabetes. 45 (Suppl 3): S45-6. doi:10.2337/diab.45.3.s45. PMID   8674889.
  10. ↑ Clément L, Poirier H, Niot I, Bocher V, Guerre-Millo M, Krief S, Staels B, Besnard P (2002). "mice fed a diet enriched in t10,c12-CLA (0.4% w/w) for 4 weeks developed lipoatrophy, hyperinsulinemia, and fatty liver, whereas diets enriched in c9,t11-CLA and LA had no significant effect ; from google (hyperinsulinemia trans fat) result 2". J Lipid Res. 43 (9): 1400–09. doi: 10.1194/jlr.M20008-JLR200 . PMID   12235171.
  11. ↑ "Physiologic Effects of Insulin". Archived from the original on 2016-11-19. Retrieved 2016-11-03.
  12. ↑ Matsuzawa, Y; Fanahashi T; Nakamura T (1999). "Moleculare mechanism of metabolic syndrome X: contribution of adiposcyte-derived bioactive substances". Annals of the New York Academy of Sciences. 892 (1): 146–54. Bibcode:1999NYASA.892..146M. doi:10.1111/j.1749-6632.1999.tb07793.x. PMID   10842660. S2CID   22802586.
  13. 1 2 Weyer, C; Funahachi T; Tanaka S; Hotta K; Matsuzawa Y; Pratley RE; Tataranni PA (2011). "Hypoadiponectinemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia". The Journal of Clinical Endocrinology & Metabolism. 86 (5): 1930–35. doi: 10.1210/jcem.86.5.7463 . PMID   11344187.
  14. ↑ Poloz, Y.; Stambolic, V. (2015). "Obesity and cancer, a case for insulin signaling". Cell Death and Disease. 6 (12): e2037. doi:10.1038/cddis.2015.381. PMC   4720912 . PMID   26720346.
  15. ↑ Vigneri, R.; Goldfine, I. D.; Frittitta, L. (2016). "Insulin, insulin receptors, and cancer". Journal of Endocrinological Investigation. 39 (12): 1365–1376. doi:10.1007/s40618-016-0508-7. PMID   27368923. S2CID   46524730.
  16. ↑ Arnoux, Jean-Baptiste; Verkarre, Virginie; Saint-Martin, Cécile; Montravers, Françoise; Brassier, Anaïs; Valayannopoulos, Vassili; Brunelle, Francis; Fournet, Jean-Christophe; Robert, Jean-Jacques; Aigrain, Yves; Bellanné-Chantelot, Christine; de Lonlay, Pascale (3 October 2011). "Congenital hyperinsulinism: current trends in diagnosis and therapy". Orphanet Journal of Rare Diseases. 6: 63. doi: 10.1186/1750-1172-6-63 . PMC   3199232 . PMID   21967988.
  17. 1 2 Arnoux, Jean-Baptiste; Verkarre, Virginie; Saint-Martin, Cécile; Montravers, Françoise; Brassier, Anaïs; Valayannopoulos, Vassili; Brunelle, Francis; Fournet, Jean-Christophe; Robert, Jean-Jacques; Aigrain, Yves; Bellanné-Chantelot, Christine (2011-10-03). "Congenital hyperinsulinism: current trends in diagnosis and therapy". Orphanet Journal of Rare Diseases. 6 (1): 63. doi: 10.1186/1750-1172-6-63 . ISSN   1750-1172. PMC   3199232 . PMID   21967988.
  18. ↑ "Physiologic Effects of Insulin". www.vivo.colostate.edu. Archived from the original on 2023-05-07. Retrieved 2020-09-05.
  19. ↑ Hayward, Nicholas J.; McDougall, Gordon J.; Farag, Sara; Allwood, J. William; Austin, Ceri; Campbell, Fiona; Horgan, Graham; Ranawana, Viren (2019). "Cinnamon Shows Antidiabetic Properties that Are Species-Specific: Effects on Enzyme Activity Inhibition and Starch Digestion". Plant Foods for Human Nutrition. 74: 544–552.
  20. ↑ Solomon, TP; Blannin, AK (November 2007). "Effects of short-term cinnamon ingestion on in vivo glucose tolerance". Diabetes, Obesity & Metabolism. 9 (6): 895–901. doi:10.1111/j.1463-1326.2006.00694.x. PMID   17924872. S2CID   10443919.
  21. ↑ Villegas, R; Gao, YT; Yang, G; Li, HL; Elasy, TA; Zheng, W; Shu, XO (January 2008). "Legume and soy food intake and the incidence of type 2 diabetes in the Shanghai Women's Health Study". The American Journal of Clinical Nutrition. 87 (1): 162–7. doi:10.1093/ajcn/87.1.162. PMC   2361384 . PMID   18175751.
  22. ↑ Weyer, C.; Hanson, R. L.; Tataranni, P. A.; Bogardus, C.; Pratley, R. E. (2000-12-01). "A high fasting plasma insulin concentration predicts type 2 diabetes independent of insulin resistance: evidence for a pathogenic role of relative hyperinsulinemia". Diabetes. 49 (12): 2094–2101. doi: 10.2337/diabetes.49.12.2094 . ISSN   0012-1797. PMID   11118012.
  23. 1 2 3 4 Solomon, Thomas P; Haus JM; Kelly KR; Cook MD; Riccardi M; Rocco M; Kashyap SR; Barkowkis H; Kirwan JP (2009). "Randomized trial on the effects of a 7-d low-glycemic diet and exercise intervention on insulin resistance in older obese humans". Am J Clin Nutr. 90 (5): 1222–29. doi:10.3945/ajcn.2009.28293. PMC   2762157 . PMID   19793849.
  24. ↑ Lund, S; Holman GD; Schmitz O; Pedersen O (1995). "Contraction stimulates translocation of glucose transporter GLUT4 in skeletal muscle through a mechanism distinct from that of insulin". Proc. Natl. Acad. Sci. U.S.A. 92 (13): 5817–5821. Bibcode:1995PNAS...92.5817L. doi: 10.1073/pnas.92.13.5817 . PMC   41592 . PMID   7597034.
  25. ↑ Erion, Karel A.; Corkey, Barbara E. (June 2017). "Hyperinsulinemia: a Cause of Obesity?". Current Obesity Reports. 6 (2): 178–186. doi:10.1007/s13679-017-0261-z. ISSN   2162-4968. PMC   5487935 . PMID   28466412.
  26. ↑ Demirbilek, Hüseyin; Hussain, Khalid (2017-12-30). "Congenital Hyperinsulinism: Diagnosis and Treatment Update". Journal of Clinical Research in Pediatric Endocrinology. 9 (Suppl 2): 69–87. doi:10.4274/jcrpe.2017.S007. ISSN   1308-5735. PMC   5790328 . PMID   29280746.
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