Ketogenic Diet. Recently, Caron et al. CAS Enahncement PubMed Central Google Scholar Kraemer, F. Metformin is Insulin sensitivity enhancement formula most Insulin sensitivity enhancement formula used eenhancement therapeutic agent for type 2 diabetes mellitus T2DM. Importance of changes in adipose tissue insulin resistance to histological response during thiazolidinedione treatment of patients with nonalcoholic steatohepatitis. Ten min later, the floating top layer containing mature adipocytes was collected.

Insulin sensitivity enhancement formula -

The differences in estimates of adipose tissue insulin sensitivity could arise from differences in growth hormone GH 20 or catecholamines. GH secretion and catecholamine sensitivity decrease with age 21, 22 , which could explain lower fasting FFA concentrations for any given insulin concentration in older subjects.

Similarly, exercise and physical fitness increase GH secretion and catecholamine responsiveness and therefore explain greater fasting FFA concentration at a certain insulin level in subjects with better physical fitness 23, The impact of GH on lipolysis argues in favor of using the pancreatic clamp technique, in which somatostatins inhibit GH secretion, thereby circumventing the effects of differences in GH secretion and GH-mediated lipolytic action.

In addition, somatostatins could also have inhibitory effects on epinephrine secretion In contrast with GH and catecholamines, glucagon is unlikely to explain the effects of age and physical fitness, because glucagon has little effect on lipolysis at physiological concentrations We also found a good correlation between IC 50 estimated by the multistep pancreatic and the one-step hyperinsulinemic-euglycemic clamp technique.

Therefore, the one-step hyperinsulinemic-euglycemic clamp is a reasonable alternative to the multistep pancreatic clamp. The one-step hyperinsulinemic-euglycemic clamp is more widely available and reduced the duration of the study.

In addition, in studies applying the one-step hyperinsulinemic-euglycemic clamp for other primary outcomes, estimates of adipose tissue insulin sensitivity can be obtained as a secondary outcome.

However, the insulin dose applied for the clamp is crucial. The dose-response relationship between insulin concentration and lipolysis is very steep in insulin-sensitive individuals; therefore, the dose applied may be greater than necessary for a maximal suppression of lipolysis outside the linear part of the log-log curve.

This would lead to an underestimation of adipose tissue insulin sensitivity, which may also have been the case for some of the subjects in the current study, thereby explaining the less than ideal agreement between IC 50 as measured by the multistep and the one-step clamp.

This could potentially be overcome by selecting an insulin dose of approximately one-half of that used for our day 2 study. However, this cannot be determined from our current data, because the dose-response relationship is determined from only two data points basal and clamp , whereas the multistep clamp with three data points would reveal a lack of linearity.

We acknowledge that when studying a population with large variations in adipose tissue insulin sensitivity, it may be difficult to obtain useful data for all subjects with only a single insulin dose.

There are limitations to our study. First, although our study covered wide ranges in age, adiposity, physical fitness, and adipose tissue insulin sensitivity, we included only two subjects with type 2 diabetes.

This limits our ability to extend our findings to patients with this disease. Second, our subjects consumed a controlled three-day diet before each study day, and our data may not apply to studies that do not include a carefully controlled diet.

In conclusion, Adipo-IR estimates adipose tissue insulin sensitivity reasonably well compared with a multistep pancreatic clamp with FFA tracers. This supports the use of Adipo-IR for larger population studies. However, Adipo-IR cannot substitute the direct measurements of insulin action in adipose tissue obtained by the clamp techniques, and this direct measurement is preferred for mechanistic studies of insulin action in adipose tissue.

In addition, if our findings can be reproduced, we suggest that age and physical fitness might be needed as part of more robust models of adipose tissue insulin sensitivity when using Adipo-IR. Finally, the one-step hyperinsulinemic-euglycemic clamp technique is a reasonable and more convenient alternative to the multistep pancreatic clamp technique in studies with other primary outcomes.

We are grateful for the excellent assistance provided by Barbara Norby and Pamela Reich with respect to subject recruitment and performance of the studies. We acknowledge the excellent technical assistance provided by Christy Allred, Debra Harteneck, and Lendia Zhou.

This work was supported by National Center for Research Resources Grant 1UL1RR; National Institutes of Health Grants DK, DK, DK; and grants from The Danish Diabetes Academy supported by the Novo Nordisk Foundation, Danish Diabetes Association, Augustinus Foundation, and the Research Council Aarhus University Hospital.

Author contributions: E. performed the studies, analyzed the data, and wrote the manuscript. and M. performed the studies, contributed to the discussion, and reviewed and edited the manuscript. designed and oversaw the study, and reviewed and edited the manuscript.

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Insulin regulation of lipolysis in nondiabetic and IDDM subjects. Gastaldelli A , Harrison SA , Belfort-Aguilar R , Hardies LJ , Balas B , Schenker S , Cusi K. Importance of changes in adipose tissue insulin resistance to histological response during thiazolidinedione treatment of patients with nonalcoholic steatohepatitis.

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Volume Article Contents Abstract. Journal Article. How to Measure Adipose Tissue Insulin Sensitivity. Esben Søndergaard , Esben Søndergaard. Oxford Academic. Ana Elena Espinosa De Ycaza. Maria Morgan-Bathke. Michael D. PDF Split View Views. Cite Cite Esben Søndergaard, Ana Elena Espinosa De Ycaza, Maria Morgan-Bathke, Michael D.

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Figure 1. Open in new tab Download slide. Table 1. Subject Characteristics. Variable a. Abbreviation: FFM, fat-free mass. Open in new tab. Figure 2. Figure 3. Figure 4. Figure 5. adipose tissue insulin resistance index.

The degree of insulin resistance should be inversely proportional to the glucose uptake by target tissues during the procedure.

In other words, the less glucose that's taken up by tissues during the procedure, the more insulin resistant a patient is. A variation of this technique, the hyperinsulinemic-hyperglycemic clamp provides a better measurement of pancreatic beta cell function but is less physiologic than the euglycemic technique.

Insulin sensitivity test IST : IST involves IV infusion of a defined glucose load and a fixed-rate infusion of insulin over approximately 3 hours. Somatostatin may be infused simultaneously to prevent insulin secretion, inhibit hepatic gluconeogenesis, and delay secretion of counter-regulatory hormones— particularly glucagon, growth hormone, cortisol, and catecholamines.

Fewer blood samples are required for this test, compared to clamp techniques. The mean plasma glucose concentration over the last 30 minutes of the test reflects insulin sensitivity.

Although lengthy, IST is less labor intensive than clamp techniques and the FSIVGTT. Insulin tolerance test ITT : A simplified version of IST, ITT measures the decline in serum glucose after an IV bolus of regular insulin 0. Several insulin and glucose levels are sampled over the following 15 minutes depending on the protocol used.

The ITT primarily measures insulin-stimulated uptake of glucose into skeletal muscle. Because this test is so brief, there's very little danger of counter-regulatory hormones interfering with its results. IV access should be established for insulin injection, blood sampling, and for rapid administration of D50W should severe hypoglycemia occur.

These values reflect the rate of decline of log transformed glucose values. Frequently sampled IV glucose tolerance tests FSIVGTT. This method is less labor intensive than clamp techniques yet still requires as many as 25 blood samples over a 3-hour period, and a computer-assisted mathematical analysis.

Several variations of the FSIVGTT have been published. One recently published study infused 0. The SI was calculated by a computer-based program. Tolbutamide administration can also be used during FSIVGTT to augment endogenous insulin secretion and is particularly useful in women with diabetes.

Continuous infusion of glucose with model assessment CIGMA : Like ITT, CIGMA requires fewer venipunctures and is less laborious than clamp techniques.

A constant IV glucose infusion is administered, and samples for glucose and insulin are drawn at 50, 55, and 60 minutes. A mathematical model is then used to calculate SI. The results are reasonably compatible with clamp techniques; however, few laboratories have used CIGMA for insulin sensitivity testing in diabetic patients and there is no substantive data using the CIGMA technique in women with PCOS.

Oral glucose tolerance test OGTT : OGTT, a mainstay in the diagnosis of impaired glucose tolerance IGT and diabetes mellitus in pregnant and nonpregnant women, may be used to assess insulin sensitivity as well.

Because no IV access is needed, OGTT is better suited for assessment of large populations than the other techniques we outlined. A modified OGTT that uses a or g glucose load and measures glucose and insulin at various intervals over 2 to 4 hours has been used in clinical studies.

Like other minimal approaches to diagnosis, OGTT provides information on beta cell secretion and peripheral insulin action, and various mathematical equations have been used to provide an SI value.

Insulin resistance has also been assessed qualitatively if one or more insulin values exceed an upper limit of normal at appropriate intervals. Researchers have compared various methods for assessing insulin sensitivity in type 2 diabetics using the OGTT and found good correlations between AUCinsulin, insulin level at minutes I , and the steady state plasma glucose concentrations derived from a modified ITT.

As mentioned before, the search for uncomplicated and inexpensive quantitative tools to evaluate insulin sensitivity has led to development of fasting state homeostatic assessments. These tests are based on fasting glucose and fasting insulin, and use straightforward mathematical calculations to assess insulin sensitivity and beta cell function.

Several homeostatic approaches have been developed in recent years, each with its merits and deficiencies. One of the weaknesses of these models is that they assume the relationship between glucose and insulin is linear when in fact it's parabolic. Fasting insulin I0 : Fasting serum insulin is an inexpensive assay, and does not require any mathematical calculations.

At least one researcher has advocated averaging two or three readings to account for day-to-day variability. Although I0 is less variable than other fasting procedures in normoglycemic patients, clinicians must still interpret results cautiously.

Remember that insulin sensitivity is the ability of the hormone to reduce serum glucose. If fasting glucose is high—for example, in a patient with impaired glucose tolerance—that may indicate a diminished effect from circulating insulin or in severe cases of insulin resistance, diminished quantity of the hormone.

Hence I0 should not be used in glucose-intolerant or diabetic patients. The ratio of glucose to insulin is easily calculated, with lower values depicting higher degrees of insulin resistance.

Homeostatic model assessment HOMA : HOMA has been widely employed in clinical research to assess insulin sensitivity. The constant should be replaced by

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