| SPINA-GR | |
|---|---|
| Reference range | 1.41–9.00 mol/s |
| Calculator | https://doi.org/10.5281/zenodo.7479856 |
| Purpose | Medical diagnosis, research |
| Test of | Insulin sensitivity |
SPINA-GR is a calculated biomarker for insulin sensitivity. [1] [lower-alpha 1] It represents insulin receptor gain.
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)
G1: Parameter for pharmacokinetics (154.93 s/L)
DR: EC50 of insulin at its receptor (1,6 nmol/L)
GE: Effector gain (50 s/mol)
P(∞): Constitutive endogenous glucose production (150 μmol/s)
Compared to healthy volunteers, SPINA-GR is significantly reduced in persons with prediabetes and diabetes mellitus, and it correlates with the M value in glucose clamp studies, triceps skinfold, subscapular skinfold and (better than HOMA-IR and QUICKI) with the two-hour value in oral glucose tolerance testing (OGTT), glucose rise in OGTT, waist-to-hip ratio, body fat content (measured via DXA) and the HbA1c fraction. [1]
Both in the FAST study, an observational case-control sequencing study including 300 persons from Germany, and in a large sample from the NHANES study, SPINA-GR differed more clearly between subjects with and without diabetes than the corresponding HOMA-IR, HOMA-IS and QUICKI indices. [3]
Together with the secretory capacity of pancreatic beta cells (SPINA-GBeta), SPINA-GR provides the foundation for the definition of a fasting based disposition index of insulin-glucose homeostasis (SPINA-DI). [3]
In combination with SPINA-GBeta and whole-exome sequencing, calculating SPINA-GR 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). [4]
In lean subjects it is significantly higher than in a population with obese persons. [1] In several populations, SPINA-GR 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. [3]
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.
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 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.
Drugs used in diabetes treat diabetes mellitus by decreasing glucose levels in the blood. With the exception of insulin, most GLP-1 receptor agonists, and pramlintide, all diabetes medications are administered orally and are thus called oral hypoglycemic agents or oral antihyperglycemic agents. There are different classes of hypoglycemic drugs, and selection of the appropriate agent depends on the nature of diabetes, age, and situation of the person, as well as other patient factors.
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.
An insulin analog is any of several types of medical insulin that are altered forms of the hormone insulin, different from any occurring in nature, but still available to the human body for performing the same action as human insulin in terms of controlling blood glucose levels in diabetes. Through genetic engineering of the underlying DNA, the amino acid sequence of insulin can be changed to alter its ADME characteristics. Officially, the U.S. Food and Drug Administration (FDA) refers to these agents as insulin receptor ligands, although they are usually just referred to as insulin analogs or even just insulin.
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.
The quantitative insulin sensitivity check index (QUICKI) is derived using the inverse of the sum of the logarithms of the fasting insulin and fasting glucose:
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.
Acquired generalized lipodystrophy (AGL), also known as Lawrence syndrome and Lawrence–Seip syndrome, is a rare skin condition that appears during childhood or adolescence, characterized by fat loss affecting large areas of the body, particularly the face, arms, and legs. There are four types of lipodystrophy based on its onset and areas affected: acquired or inherited, and generalized or partial. Both acquired or inherited lipodystrophy present as loss of adipose tissues, in the absence of nutritional deprivation. The near-total loss of subcutaneous adipose tissue is termed generalized lipodystrophy while the selective loss of adipose tissues is denoted as partial lipodystrophy. Thus, as the name suggests, AGL is a near-total deficiency of adipose tissues in the body that is developed later in life. It is an extremely rare disease with only about 100 cases reported worldwide. There are three main etiologies of AGL suspected: autoimmune, panniculitis-associated, or idiopathic. After its onset, the disease progresses over a few days, weeks, months, or even in years. Clinical presentations of AGL are similar to other lipodystrophies, including metabolic complications and hypoleptinemia. Treatments are also similar and mainly supportive for symptomatic alleviation. Although HIV- or drug-induced lipodystrophy are types of acquired lipodystrophy, their origins are very specific and distinct and hence are usually not discussed with AGL.
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.
Chromium is claimed to be an essential element involved in the regulation of blood glucose levels within the body. More recent reviews have questioned this, however.
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.
The Metabolic Score for Insulin Resistance (METS-IR) is a metabolic index developed with the aim to quantify peripheral insulin sensitivity in humans; it was first described under the name METS-IR by Bello-Chavolla et al. in 2018. It was developed by the Metabolic Research Disease Unit at the Instituto Nacional de Ciencias Médicas Salvador Zubirán and validated against the euglycemic hyperinsulinemic clamp and the frequently-sampled intravenous glucose tolerance test in Mexican population. It is a non-insulin-based alternative to insulin-based methods to quantify peripheral insulin sensitivity and an alternative to SPINA Carb, the Homeostatic Model Assessment (HOMA-IR) and the quantitative insulin sensitivity check index (QUICKI). METS-IR is currently validated for its use to assess cardio-metabolic risk in Latino population.
SPINA-GBeta is a calculated biomarker for pancreatic beta cell function. It represents the maximum amount of insulin that beta cells can produce per time-unit.
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.
