| SPINA-GBeta | |
|---|---|
| Reference range | 0.64–3.73 pmol/s |
| Calculator | https://doi.org/10.5281/zenodo.7479856 |
| Purpose | Medical diagnosis, research |
| Test of | Pancreatic beta cell function |
SPINA-GBeta is a calculated biomarker for pancreatic beta cell function. [1] [lower-alpha 1] It represents the maximum amount of insulin that beta cells can produce per time-unit (e.g. in one second).
The index is derived from a mathematical model of insulin-glucose homeostasis. [2] For diagnostic purposes, it is calculated from fasting insulin and glucose concentrations with:
. [1]
[I](∞): Fasting Insulin plasma concentration (μU/mL)
[G](∞): Fasting blood glucose concentration (mg/dL)
Dβ: EC50 for glucose at beta cells (7 mmol/L)
G3: Parameter for pharmacokinetics (58,8 s/L)
SPINA-GBeta significantly correlates with the M value in glucose clamp studies and (better than HOMA-Beta) with the two-hour value in oral glucose tolerance testing (OGTT), glucose rise in OGTT, subscapular skinfold, truncal fat content and the HbA1c fraction. [1]
It has the additional advantage that it circumvents the HOMA-blind zone, which renders the calculation of HOMA-Beta impossible if the fasting glucose concentration is 3.5 mmol/L (63 mg/dL) or below. [3] Unlike HOMA-Beta, SPINA-Beta can be sensibly calculated in the whole range of measurements. [1]
In repeated measurements, SPINA-GBeta had higher retest reliability than HOMA-Beta, a measurement for beta cell function from the homeostasis model assessment. [1] [4]
In the FAST study, an observational case-control sequencing study including 300 persons from Germany, SPINA-GBeta differed more clearly between subjects with and without diabetes than the corresponding HOMA-Beta index. [4]
Together with the reconstructed insulin receptor gain (SPINA-GR), SPINA-GBeta provides the foundation for the definition of a fasting based disposition index of insulin-glucose homeostasis (SPINA-DI). [4]
In combination with SPINA-GR and whole-exome sequencing, calculating SPINA-GBeta helped to identify a new form of monogenetic diabetes (MODY) that is characterised by primary insulin resistance and results from a missense variant of the type 2 ryanodine receptor (RyR2) gene (p.N2291D). [5]
In several populations, SPINA-GBeta correlated with the area under the glucose curve and 2-hour concentrations of glucose, insulin and proinsulin in oral glucose tolerance testing, concentrations of free fatty acids, ghrelin and adiponectin, and the HbA1c fraction. [4]
Hypoglycemia, also called low blood sugar, is a fall in blood sugar to levels below normal, typically below 70 mg/dL (3.9 mmol/L). Whipple's triad is used to properly identify hypoglycemic episodes. It is defined as blood glucose below 70 mg/dL (3.9 mmol/L), symptoms associated with hypoglycemia, and resolution of symptoms when blood sugar returns to normal. Hypoglycemia may result in headache, tiredness, clumsiness, trouble talking, confusion, fast heart rate, sweating, shakiness, nervousness, hunger, loss of consciousness, seizures, or death. Symptoms typically come on quickly.
Insulin resistance (IR) is a pathological condition in which cells either fail to respond normally to the hormone insulin or downregulate insulin receptors in response to hyperinsulinemia.
Beta cells (β-cells) are specialized endocrine cells located within the pancreatic islets of Langerhans responsible for the production and release of insulin and amylin. Constituting ~50–70% of cells in human islets, beta cells play a vital role in maintaining blood glucose levels. Problems with beta cells can lead to disorders such as diabetes.
The glucose tolerance test is a medical test in which glucose is given and blood samples taken afterward to determine how quickly it is cleared from the blood. The test is usually used to test for diabetes, insulin resistance, impaired beta cell function, and sometimes reactive hypoglycemia and acromegaly, or rarer disorders of carbohydrate metabolism. In the most commonly performed version of the test, an oral glucose tolerance test (OGTT), a standard dose of glucose is ingested by mouth and blood levels are checked two hours later. Many variations of the GTT have been devised over the years for various purposes, with different standard doses of glucose, different routes of administration, different intervals and durations of sampling, and various substances measured in addition to blood glucose.
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 come on slowly. Long-term complications from high blood sugar include heart disease, strokes, diabetic retinopathy which can result in blindness, kidney failure, and poor blood flow in the limbs which may lead to amputations. The sudden onset of hyperosmolar hyperglycemic state may occur; however, ketoacidosis is uncommon.
The blood sugar level, blood sugar concentration, blood glucose level, or glycemia is the measure of glucose concentrated in the blood. The body tightly regulates blood glucose levels as a part of metabolic homeostasis.
Glucokinase is an enzyme that facilitates phosphorylation of glucose to glucose-6-phosphate. Glucokinase occurs in cells in the liver and pancreas of humans and most other vertebrates. In each of these organs it plays an important role in the regulation of carbohydrate metabolism by acting as a glucose sensor, triggering shifts in metabolism or cell function in response to rising or falling levels of glucose, such as occur after a meal or when fasting. Mutations of the gene for this enzyme can cause unusual forms of diabetes or hypoglycemia.
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.
Glycated hemoglobin is a form of hemoglobin (Hb) that is chemically linked to a sugar. Most monosaccharides, including glucose, galactose and fructose, spontaneously bond with hemoglobin when present in the bloodstream. However, glucose is only 21% as likely to do so as galactose and 13% as likely to do so as fructose, which may explain why glucose is used as the primary metabolic fuel in humans.
Many types of glucose tests exist and they can be used to estimate blood sugar levels at a given time or, over a longer period of time, to obtain average levels or to see how fast body is able to normalize changed glucose levels. Eating food for example leads to elevated blood sugar levels. In healthy people, these levels quickly return to normal via increased cellular glucose uptake which is primarily mediated by increase in blood insulin levels.
The homeostatic model assessment (HOMA) is a method used to quantify insulin resistance and beta-cell function. It was first described under the name HOMA by Matthews et al. in 1985.
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.
Zinc transporter 8 (ZNT8) is a protein that in humans is encoded by the SLC30A8 gene. ZNT8 is a zinc transporter related to insulin secretion in humans. In particular, ZNT8 is critical for the accumulation of zinc into beta cell secretory granules and the maintenance of stored insulin as tightly packaged hexamers. Certain alleles of the SLC30A8 gene may increase the risk for developing type 2 diabetes, but a loss-of-function mutation appears to greatly reduce the risk of 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.
Glucose clamp technique is a method for quantifying insulin secretion and resistance. It is used to measure either how well an individual metabolizes glucose or how sensitive an individual is to insulin.
Thyroid's secretory capacity is the maximum stimulated amount of thyroxine that the thyroid can produce in a given time-unit.
The sum activity of peripheral deiodinases is the maximum amount of triiodothyronine produced per time-unit under conditions of substrate saturation. It is assumed to reflect the activity of deiodinases outside the central nervous system and other isolated compartments. GD is therefore expected to reflect predominantly the activity of type I deiodinase.
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.
SPINA-GR is a calculated biomarker for insulin sensitivity. It represents insulin receptor gain.
Pancreatic beta cell function is one of the preconditions of euglycaemia, i.e. normal blood sugar regulation. It is defined as insulin secretory capacity, i.e. the maximum amount of insulin to be produced by beta cells in a given unit of time.
