Insulin Resistance - Science topic

Estimated Glucose Disposal Rate (eGDR) is a measure of insulin sensitivity that is calculated using mathematical equations based on clinical and laboratory parameters. There are several modified equations available for eGDR, as researchers and clinicians have attempted to improve its accuracy and applicability for different populations.

The modifications to eGDR equations are usually based on the data from studies that show the limitations of the original equation or its applicability to certain populations. For example, some modifications may incorporate additional clinical variables such as age, gender, ethnicity, or body mass index (BMI), which have been shown to affect insulin sensitivity. Other modifications may incorporate different laboratory measures such as fasting insulin levels or HbA1c.

The threshold for eGDR varies depending on the specific modified equation used and the population being studied. Generally, a higher eGDR indicates better insulin sensitivity, while a lower eGDR indicates decreased insulin sensitivity or insulin resistance. However, the specific threshold values for eGDR may vary depending on the population studied, as different populations may have different baseline levels of insulin sensitivity and different risk factors for insulin resistance.

Ultimately, the decision on which eGDR equation and threshold to use depends on the research question or clinical context. Researchers and clinicians should choose an equation and threshold that is appropriate for their specific population and research or clinical needs.

reference :

As the word autophagy means eating itself which is an autoimmunity and of course affected beta cells will decrease in number and some in size and some will die (necrosis).

Anorexia nervosa is a psychiatric disorder that affects approximately 1 in 100 women in the reproductive age group. It is characterised by the inability to maintain normal weight most commonly due to intense fear of weight gain. While AN is classified as a psychiatric disorder, it often causes a range of physical consequences, such as electrolyte imbalance, amenorrhea secondary to hormonal derangements, impaired haematopoiesis, and decreased grey matter in the brain. There is a common misconception that women with active AN cannot conceive because of irregular menses or amenorrhea. In response to severely restricted energy intake, the hypothalamic-pituitary–gonadal axis (HPA) may produce hormonal secretion patterns similar to prepubertal or early pubertal individuals. Luteinising hormone pulses in women with AN tend to have low pulse amplitude in general, which can result in amenorrhea. AN has a fluctuating course of illness with periods of partial recovery and deterioration. Some women with AN have irregular periods rather than amenorrhoea.

I believe the following reference is highly relevant:

German JB, Dillard CJ. Saturated fats: A perspective from lactation and milk composition. Lipids 2010; 45 (10): 915-23.

Type 1 Diabetes Mellitus is almost purely genetic but type DM pathogenesis is involved considerably with diet related almost all excessive carbohydrates taken by the person.

Hi Nawaz Khan , based on my experiment, i found the insulin concetration is important in inducing adipogenesis. I firstly used 1 ug/ml insulin in induced-medium, the result is not good. Then I tried 10ug/ml insulin (the concentrations of IBMX and DEX are the same as yours), the adipogenesis is visible to naked eyes after 48 hours, but the cells' ability of adhering is weakened, so i treated them very very tenderly. Some researchers recomand 1-10ug/ml insulin. Maybe you can try higher insulin concentration, like 5 ug/ml or 10ug/ml. Wish you luck~

Also check please the following useful RG links:

best index been homeostasis model assessment of insulin resistance (HOMA-IR)

Less physical activity may be more important than excessive eating for the development of insulin resistance in human body

Hello.

For Glucose sensitivity test and start the test first hour in the morning, after overnight fasting. For the Insulin sensitivity test we withdraw the food at the first hour in the morning and start the test one hour later.

Evidence:

Putri Elisa Md

The JBI checklist is the most popular of these three tools. Typically, a descriptive cross-sectional research is done to determine illness prevalence and incidence. As a result, the critical appraisal instrument for analytic cross-sectional study is inappropriate for the evaluation.

The goal of this assessment is to evaluate a research's methodological quality and to identify how well a study handled the risk of bias in its design, conduct, and analysis.

You can feed them with a high fat diet until they are diabetic. Animal feed producers can make the special food upon request.

Dear Natalia,

I wish this article is helpful

It is an interesting question but I have not heard of such test. If it dives indication of Insulin resistance, then it would be useful.

@Amos Thank you for the information

We would use a 3U/Kg i.p. dose of insulin in fasted animals (5hrs as overnight fasting is very stressful for mice). Tissue is harvested 15 mins post injection.

Hi Pourya,

Do you change the fructose solution, at least once, but preferably twice a week? I feed my mice a 32% fructose solution (D-fructose diluted in tap water and sterile filtered) and I find they have no problem drinking it, but you have to change the solution and the bottles regularly as two things can happen: the solution dries in the spout and blocks it, or that the solution starts to smell bad - the solution has a high concentration of sugar so it shouldn't get contaminated, but I have noticed the smell changes.

Hope this helps!

As mentioned, it could be palatability. However, you could also use special HFD or HFHS diets to induce insulin resistance in your rats.

TFA intake is directly associated with the development of diabetes mellitus (DM) remains unknown.

Some genetic factors

Lipolysis in the consequence of basal insulin defiency

(Keto-)Acidosis,

Some hormones (like growth hormone and others)

Some drugs, mostly hormones itself (e. g. cortisone)

Insulinreceptor-Down-regulation

Antibodies against insulin and its receptor

Liver cirrhosis

Thank you, agreed with Mitchell V Kaminski , but it is not universal, some people never develop diabetes despite doing the same (overconsumption of refined sugar). Where is the defect that brought some to suffer from diabetes while the same is not observed in their counterparts?

Also check https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4855031/

The TyG index was evaluated as a surrogate method for estimation of insulin resistance and it proved to perform better than HOMA in recent research

From this possibility you can influence the amount of M2

Perhaps the “ESPGHAN/ESPEN/ESPR guidelines on pediatric parenteral nutrition: Carbohydrates” and related publications provide the appropriate and practical instructions for glucose infusion in children [1]. Excessive chronic glucose infusion may lead to hyperglycemia, which leads to increased lipogenesis and adipocyte fat deposition along with subsequent hepatic steatosis, elevated hepatic VLDL triglycerides, hypercholesterolemia, and may ultimately cause insulin resistance (IR) [1]. The magnitude of this effect depends individually and is affected by pre-existing metabolic stress or disease [1]. The gold standard for determining IR is the euglycemic–hyperinsulinemic clamp technique [3]. This method is considered invasive, costly, and impractical for large samples. Despite its modest specificity and sensitivity, HOMA-IR is used as an IR surrogate and alternative index in a large number of studies, including those dealing with children [4]. Other IR indexes with varied specificity and sensitivity, as well as purposes, are available [3,4].

References:

[1] Mesotten D, Joosten K, Kempen A, et al. ESPGHAN/ESPEN/ESPR guidelines on pediatric parenteral nutrition: carbohydrates. Clinical Nutrition, 2018; xxx: 1-7. http://dx.doi.org/10.1016/ j.clnu.2018.06.947.

[2] Sanchez-Garc´ıa A, Rodr´ıguez-Gutierrez R, Mancillas-Adame L. et al. Diagnostic accuracy of the triglyceride and glucose index for insulin resistance: a systematic review. International Journal of Endocrinology, 2020; ID 4678526, 7 pages. https://doi.org/10.1155/2020/ 4678526.

[3] van der Aa Marloes P, Catherijne AJK, Anthonius dB, et al. Definition of insulin resistance affects prevalence rate in pediatric patients: a systematic review and call for consensus. Journal of Pediatric Endocrinology and Metabolism, 2017; 30(2):123-131.doi:10.1515/jpem-2016-0242.

The fact that cancer cells use more sugar than non-cancer cells, known as the Warburg effect, appears to form the basis of the current question. Nevertheless, it is not yet known if this effect is merely a symptom of cancer or whether it is the cause of cells becoming cancerous. Evidence indicating the way cancer cells metabolize sugar is not conclusive, either. Considering refined or added sugar, the bulk of the available evidence indicates that sugar is not a carcinogen. There is no evidence that eating sugar causes cancer or speeds up its growth. There is also no evidence that eliminating dietary sugar causes cancer to shrink or disappear. However, it is known that eating excess sugar, especially added sugars, can contribute to many chronic diseases such as obesity and diabetes, which are potential risk factors for several types of cancer.

Chromium picolinate, specifically, has been shown to reduce insulin resistance . Chromium levels decrease with age. Studies show that people with type 2 diabetes have lower blood levels of chromium than those without the disease

Dear Vishnu, I usually always perform both ITT and OGTT, you can add IPGTT if you are trying to assess the role of incretins. Some of your animals may be insulin resistant only or glucose intolerant only, having the two tests is essential to clearly monitor what is the physiopathology. Plus, unlike mice, Wistar are outbred rats that will result in higher variability among the animals.

Ziegelasch, N., Vogel, M., Müller, E. et al. Cystatin C serum levels in healthy children are related to age, gender, and pubertal stage. Pediatr Nephrol 34, 449–457 (2019). https://doi.org/10.1007/s00467-018-4087-z

Aisling Smyth

Dear colleague,

there are unfortunately no cutoff value. My suggestion, whatever the aim of you work is, is to provide quartiles or quintiles of HOMA-IR in your descriptive statistics. This is the most widely used methods when discussing HOMA index.

If you need a cutoff for any kind of binary statistics, the most reliable paper would probably be the one from Ascaso and colleagues (Diabetes Care 26:3320–3325, 2003).

Interesting question. Rodent studies have indeed showed dose dependent increase of calcitonin in clinically relevant doses. However, the relevance of rodent models with humans is unknown. Long term epidemiological studies will be needed in order to have a reliable answer. In the meantime, FDA recommends avoidance of use of these drugs in patients diagnosed with medullary thyroid cancer, patients with familial history of medullary cancer, or MEN2. Indeed, it is difficult to have a reliable family history on syndromes of multiple endocrine neoplasms. In the meantime, FDA recommends calcitonin measurement and thyroid ultrasound in patients treated with GLP1 receptor agonists. There are also a few case reports of people that were diagnosed with medullary thyroid carcinoma while being on GLP1 receptor agonist treatment. However, it is not straightforward to prove causality. Registries of patients with medullary thyroid carcinoma will be helpful in providing an answer. In rodents, the development of medullary thyroid carcinoma had a significant latency, about 25% of rodent life time was needed for the diagnosis of medullary carcinoma. Thus, pharmacovigilance is needed and careful consideration before prescription of GLP1 receptor agonists in children.

Hi,

always used only high-fat diet, or high- proten or high -fiber ,according to experimental models from previous studies. But usually we use one or the other.

Thank you!

Polycystic ovarian disease (PCOD) is widely dependent on genetic, environmental, lifestyle and ethnicity factors including body weight. Weight loss improves the endocrine profile and increases chances of ovulation and pregnancy.

Hi Laith,

you must see this paper from DiabetesCare (https://care.diabetesjournals.org/content/26/8/2442) to see its role on IR/IS. It is well known to be measured in human as a markers for metabolic syndromes but even though it could be interesting to use it to overcome such diseases, since adiponectin can have other roles in cells (as anti-inflammatory effects, reproduction changes, cancer onset...), lifetime changes should produce more risky results (nutrition, sports...) than use of hormones.

fred

Diabetes is frequently associated with magnesium (Mg) deficit.

HOMA is the best method to calculate insulin resistance.

Hi Mohamed

I think you're searching for this paper ( ) and related ones.

fred

There are existing data on the metabolic and endocrine effects of dietary fructose that suggest that increased consumption of fructose may be detrimental in terms of body weight and adiposity and the metabolic indexes associated with the insulin resistance syndrome,

Please look for this link:

Prince Nkemakolam Okoroh yes, you're right... but what if this scenario could be maintained without further treatment, would it mean that the treatment worked and the person is now free of T2DM?

Thanks Zainab

I would suggest you ask Prof. Melvin Hayden. He is a participant on Researchgate. Good luck!

Hi Fahrettin,

What you are describing is relatively common. I recommend you look for your gene at http://www.mousephenotype.org/ to see if other knockouts have been subjected to systematic phenotyping by the IMPC.

If what you say is correct (both are pure C57Bl/6 background), there can be many explanations including CRISPR off-target effects. Try looking at flanking genes to see if it would make sense that introducing genetic elements might have disturbed transcription factor binding sites, then check the expression of those genes by qPCR. It's good also to look carefully at the targeting strategies to be sure that they will be complete knockouts and that all mRNA variants will be affected including those with alternative start codons.

PCOS is heavily linked to insulin resistance. With the rise of non-communicable diseases globally including type 2 diabetes and metabolic syndrome, the incidence of PCOS is expected to also increase considerably.

A very interesting exchange. I refer you all to a new review i had written on how hyper-insulinemia can cause insulin resistance (Najjar and Perdomo, Physiology, May issue-2019).

Mario Ciampolini thank you

Great question. While certainly a key player in macrophage recruitment to adipose tissue and subsequent inflammation, I would just like to point out that there is certainly conflicting evidence as to whether LPS is required for the systemic glucose/insulin intolerance that we observe with endotoxemia. Have a look at this 2012 paper which used a model of reduced LPS-immunogenicity for comparison.

Although, I'm sure others may be able to contribute something more recent in the literature.

Hi Maiara,

ITT protocols vary, but as rule mice need to fast before insulin injection, in order to bring mice to a similar level of blood glucose, because you do not know the last time they have eaten. You should not offer food again.

Protocol variation is usually about fasting time (again, for mice you should not go beyond 4-6h). Otherwise, they are subjected to hypoglycemia after insulin ip. The second variation is the insulin dose (from 0,5-1,0 IU/Kg), depending on mice strain.

See if the attachments can help you.

Inherited metabolic disorders are genetic conditions that result in metabolism problems. If it's can considered as linking so most people with inherited metabolic disorders have a defective gene that results in an enzyme deficiency. There are hundreds of different genetic metabolic disorders, and their symptoms, treatments, and prognoses vary widely.

These might be helpful...

I guess IT CAN, but still diabetes remain the disease of lifestyle, so NOT ALWAYS

Get a look on this paper please. May be it will help:

Dear Mikolaj,

This is a great question. We are well known that most of our body cells have glucose transporter system which mostly mediated by insulin. However, a number of cells uptakes glucose without insulin mediation. Thus, in hyperglycaemic conditions such as insulin resistance these cells are more affected and most of diabetes complications observe in these cells due to glucose over uptake ...thus, midlife type 2 diabetes was not simply a vascular risk factor but rather had a more general negative effect on brain integrity. It could directly affect nerve cell and synapse physiology, perhaps by enhancing Alzheimer-type neurodegeneration, or the loss of brain volume could be separate though additive with Alzheimer pathology.

All the best,

Dear Terun,

Maybe the following reviews will help you on the subject:

Xun P, Wu Y, He Q, He K. Fasting insulin concentrations and incidence of hypertension, stroke, and coronary heart disease: a meta-analysis of prospective cohort studies. Am J Clin Nutr 2013;98(6):1543-54. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3831539/pdf/ajcn9861543.pdf

Zhang X, Li J, Zheng S, Luo Q, Zhou C, Wang C. Fasting insulin, insulin resistance, and risk of cardiovascular or all-cause mortality in non-diabetic adults: a meta-analysis. Biosci Rep 2017;37(5):BSR20170947. http://www.bioscirep.org/content/37/5/BSR20170947.full-text.pdf

Best regards from Germany,

Martin

Thank you all very much for your recommendations and research papers to read and reference. I really appreciate it!

Best regards,

Kiera

Dear Pranab

Good day. As for as mechanism of insulin resistance in type-2 diabetes mellitus is concerned, I think the basic evidence emerged when researchers observed that hyperglycemia was associated with higher than normal insulin, which implied that the hyperinsulinemia was unable to dispose of the glucose. This led to the concept of “insulin resistance”.

Now your question needs underlying mechanism in subjects with insulin resistance. Coming to this, first its not just ATP to blame, the defects seem to have molecular basis leading to changes in both insulin receptor and further downstream effect.

The normal physiological insulin-insulin receptor pathway is depicted as: (ATTACHED AS FIGURE-1)

So pathology can result from beta cell dysfunction, insulin release kinetics, insulin, insulin receptor and further downstream actors.

1- Vollenweider P et al have demonstrated defects in downstream pathways affecting insulin receptor substrate (IRS) related phosphatidylinositol 3 (PIP3) activation, which further inhibits the PKC protein due to decrese tyrosine kinase phosphorylation.

Reference: Vollenweider P et al. Insulin resistance, defective insulin receptor substrate 2-associated phosphatidylinositol-3' kinase activation, and impaired atypical protein kinase C (zeta/lambda) activation in myotubes from obese patients with impaired glucose tolerance. Diabetes. 2002 Apr;51(4):1052-9.

2- Another pathway highlighted along with Vollenweider et al is that of p42(MAPK) & p44(MAPK) tyrosine phosphorylationwhich can lead to decrease glucose related uptake of glucose.

Reference: del Aguila LF et al. TNF-alpha impairs insulin signaling and insulin stimulation of glucose uptake in C2C12 muscle cells. Am J Physiol.1999 May;276(5 Pt 1):E849-55.

3- Mutations in insulin receptor are also common in diabetes.

Reference: Kusari J et al. Insulin resistance and diabetes due to different mutations in the tyrosine kinase domain of both insulin receptor gene alleles. J Biol Chem. 1991 Mar 15;266(8):5260-7.

4- Apart from glucose insulin resistance is also implicated in disturbing lipid metabolites leading to their ectopic deposition and poor folding of several protein and effects on immune response with increase release of inflammatory cytokines.

Reference: Samuel VT et al. Mechanisms for insulin resistance: common threads and missing links. Cell. 2012 Mar 2;148(5):852-71. doi: 10.1016/j.cell.2012.02.017.

Finally pubmed data search as ome of which I have highlighted will provide you with enormous specific defects in insulin release in type-2 diabetes. Moreover, the evolving field of molecular pathology is discovering newer and newer mutations which actually play the producer and director’s role behind these apparent mechanisms. Much more to decipher in terms of molecular parthenogenesis.

Regards

Dr Sikandar

Thanks a lot José Fernando Díaz-Villanueva

But are there other contributors to PCOS other than insulin resistance because the points you mentioned are related to insulin resistance.

I have seen very typical PCOS phenotypes but with no insulin resistance or whatsoever, so can there be other factors leading to this PCOS phenotype?

Some genetically modified tendencies?

Some other diseases causing PCOS like patterns??

Regards

Dr Sikandar

Hi Andrew

i detailled below the protocol i used to induce insulino-resistance and assay 2-NBDG cell incorporation. Unfortunally, the values that i obtained was the same. is there any modifications i should do?

2-NBDG glucose uptake assay on insulin-resistant HepG2 cells

- Culture cells (2 x 104/well) in a black clear bottom 96-well microtiter plate in a final volume of 100 µL/well in presence of additional factors for viability/proliferation testing.

- Incubate cells overnight or 80-90% of confluence. The appropriate incubation time will depend on the individual cell type and cell concentrations used.Therefore, it is recommended to determine the optimal incubation time for a particular experiment.

- Carefully remove (decant) the overnight culture medium from adherent cells and add in each wells 100µL of fresh medium (without growth factors: FBS) containing 1 µM insulin in serum-free MEM (5.5 mM Glucose)

- Incubate the plate at 37°C for 24 hours in a humidified, 5% CO2 atmosphere

- Carefully remove (decant) the overnight culture medium from adherent cells and add in each wells 100µL of fresh medium low glucose (without growth factors: FBS) containing for each well the amount of sample (concentration) need for the experiment

- Incubate the plate at 37°C for 24h in a humidified 5% CO2 atmosphere

- Carefully remove (decant) the culture medium containing samples from adherent cells and add in each wells 100µL of fresh medium low glucose (without growth factors: FBS) containing 0.1 µM insulin in serum-free MEM (5.5 mM glucose)

- Incubate the plate at 37°C for 30 minutes in a humidified 5% CO2 atmosphere

- Then, add in each wells 100 µL of 2-NBDG (40 µM) prepared on PBS (1% BSA)

- Incubate the plate at 37°C for 30 minutes in a humidified 5% CO2 atmosphere

- Washed cells two times with 200 µL of ice-cold PBS to stop uptake

- Add in each wells 100 µL of PBS

- Measure the 2-NBDG fluorescence intensity on a fluorescence microplate reader at 465 nm excitation and 540 nm emission wavelengths.

Sikandar, yes, most MD doctors are testing hemoglobin A1C which is glycated red blood cells. Since RBC live for 3 months the hgA1c gives, a pretty good average of fasting glucose for the last 3 months. Glycated proteins produce AGE Advanced Glycated End products that accelerate aging. And then there is glycated insulin, that will be the most important test in the future - see:

Maybe the following papers will help you:

1. Shi-Xiong Tan, Kelsey H. Fisher-Wellman, Daniel J. Fazakerley, Yvonne Ng, Himani Pant, Jia Li, Christopher C. Meoli, Adelle C. F. Coster, Jacqueline Stöckli§4, and David E. James. Selective Insulin Resistance in Adipocytes. THE JOURNAL OF BIOLOGICAL CHEMISTRY VOL. 290, NO. 18, pp. 11337–11348, May 1, 2015

2. Zechner R, Zimmermann R, Eichmann TO, et al. FAT SIGNALS - Lipases and Lipolysis in Lipid Metabolism and Signaling. Cell Metabolism. 2012;15(3):279-291. doi:10.1016/j.cmet.2011.12.018.

3. Philip G. McTernan, Alison L. Harte, Leah A. Anderson , Allan Green, Stephen A. Smith, Julie C. Holder, Anthony H. Barnett, Margaret C. Eggo, Sudhesh Kumar. Insulin and Rosiglitazone Regulation of Lipolysis and Lipogenesis in Human Adipose Tissue In Vitro.Diabetes May 2002, 51 (5) 1493-1498 .

I hope this link will help you

regards

I’m curious, what method did you end up using? I’m currently using the iSTAT device to measure different blood gases along with lactate, but I‘m seeing odd lactate levels, even in my control mice. Taking blood from a cardiac puncture during harvest and immediately analyzing. Wondering if there is a more accurate way to measure for mice as this device is typically used for human patients.

If it may help...

Popović-Djordjević J.B., Jevtić I.I., Stanojković, T. P. (2018) Antidiabetics: Structural Diversity of Molecules with a Common Aim, Current Medicinal Chemistry.

DOI : 10.2174/0929867325666171205145309

Dear Carlos

Epinex is developping a test for glycated albumin. Not yet FDA approved.

provide devices for POC measurement of Hb A1c that I am aware of. I am sure there are more on the market. Kind regards, Michaela

Dear Abdul,

Maybe the following papers will help you:

Moore DJ, Gregory JM, Kumah-Crystal YA, Simmons JH. Mitigating micro-and macro-vascular complications of diabetes beginning in adolescence. Vasc Health Risk Manag 2009;5:1015-31. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2788594/pdf/vhrm-5-1015.pdf

Zimmerman RS. Diabetes Mellitus: Management of Microvascular and Macrovascular Complications. Cleveland Clinic - Center for Continuing Education. 2016. http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/endocrinology/diabetes-mellitus/

Donaghue KC, Wadwa RP, Dimeglio LA, Wong TY, Chiarelli F, Marcovecchio ML, Salem M, Raza J, Hofman PL, Craig ME; International Society for Pediatric and Adolescent Diabetes. ISPAD Clinical Practice Consensus Guidelines 2014. Microvascular and macrovascular complications in children and adolescents. Pediatr Diabetes 2014;15 Suppl 20:257-269. http://www.asped.org/chapters/18-Microvascular%20and%20macrovascular%20complications%20in%20children%20and%20adolescents.pdf

Hewapathirana N, Page S. Diabetic microvascular complications – screening, diagnosis and prevention. Clinical Focus Primary Care 2012, 6 (3): 177-191. https://www.google.de/url?sa=t&rct=j&q=&esrc=s&source=web&cd=13&ved=0ahUKEwjK_YiMrZPZAhWQKewKHZ-UATk4ChAWCDgwAg&url=http%3A%2F%2Fwww.ipcauk.org%2Findex.php%2Fclinical-focus-primary-care%2Fcf-volume-6-n3%2Fitem%2Fdownload%2F143_947f4c33d253d8846681d07f82404884&usg=AOvVaw2QlSY0XXz2o9bgiy3l-Y9i

All the best,

Martin

I completly agree that insulin sensitivity is very dinamically altered by many physiologically or pathologic conditions. In dogs, secondary diabetes as result of higuer progesterone and GH levels is very commom during diestrus in intact females. When we remove the source of those antagonic hormonal stimuli, many bitches achiev diabetes remission, sometimes few days after surgery. This paper may help...

No, HOMA and QUICKI basically reflect hepatic insulin resistance while the measures after a glucose challenge rather reflect whole body insulin resistance (muscle, fat etc) or beta cell function. There are other indices for insulin/glucose dynamics such as insulinogenic index, matsuda etc

see

Dr. Hyden, this is a very recent multidisciplinary project, we are working on the identification of the components of the sample through chromatography, spectrometry and magnetic resonance. We are starting studies in the hyperglycemic mouse with a skin lesion that includes the destruction of the epidermis and deep dermis. We intend to evaluate the regenerative activity of the skin layers, vascularization, etc., in these animals treated with the substance. We do not have publications so far and we are looking for financing to continue advancing in the coming years. So we keep in communication by RG or email (rogarcia@uacam.mx)

The link is an association not causal. Do patients who are more likely to use sweeteners have the profile of people who would tend to have higher rates of insulin resistance?- confounder, not causal.

Even if it is causal, then the signal is not very strong.

Just an opinion.

perhaps

HOMA-IR for insulin sensitivity have been shown to have a modest and weaker correlation for estimating insulin sensitivity in mice and rats in comparison to humans and it may be due to a considerable difference in murine physiology. If insulin sensitivity is the primary outcome of whatever you are studying it is recommended that you use the clamp studies instead. There are interesting articles pairing the two methods that you could take a look at: