Metformin and insulin sensitivity -
This points to the possibility that SHORT syndrome model might be useful for further research into the insight of metformin action. There are also clinical implications of our case. Doctors very rarely perform glucose tolerance tests on metformin, as this agent is usually stopped prior to testing, in order to avoid possible false negative results.
Furthermore, in most cases OGTT is performed without concomitant insulin measurements. In this case we performed the second OGTT on metformin in order to assess the extent of improvement of insulin resistance in this case of rare genetically-determined disease associated with severe insulin resistance.
Paradoxically we observed worsening of glucose tolerance with a massive release of insulin above the assay detection limit. If the second Oral Glucose Tolerance Test i. on metformin treatment had not been performed, then subsequent worsening of glucose tolerance, or even early development of type 2 diabetes would have been most likely attributed to beta-cell exhaustion due to genetically-determined insulin resistance, rather to superimposed effects of metformin treatment, that would have been missed.
In case of the SHORT syndrome, most available literature data [ 1 , 2 , 4 , 12 , 13 ] pertain to either genetic or clinical characteristics of disease with hardly any data on treatment modalities and outcome. For instance, in an extensive genetic paper by Huang-Doran et al.
Verge et al. The case of our patient therefore constitutes a caution for clinicians, who treat insulin-resistant states, where metformin is usually a drug of the first choice. SHORT syndrome might represent an exception from this rule. Indeed, at least in some of these patients metformin treatment might worsen, rather than improve, glucose tolerance, and paradoxically accelerate an onset of type 2 diabetes.
In view of these findings we postulate that SHORT syndrome might be a model to test yet unknown aspects of metformin actions. As the study comprises a case report, then no formal database has been created. Chudasama KK, Winnay J, Johansson S, Claudi T, König R, Haldorsen I, Johansson B, Woo JR, Aarskog D, Sagen JV, Kahn CR, Molven A, Njølstad PR.
SHORT syndrome with partial lipodystrophy due to impaired phosphatidylinositol 3 kinase signaling. Am J Hum Genet. Article CAS Google Scholar. Innes AM, Dyment DA. SHORT syndrome. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K, Amemiya A, editors. SourceGeneReviews ®.
Seattle: University of Washington; — Højlund K. Metabolism and insulin signaling in common metabolic disorders and inherited insulin resistance. Dan Med J. PubMed Google Scholar. Avila M, Dyment DA, Sagen JV, St-Onge J, Moog U, Chung BHY, Mo S, Mansour S, Albanese A, Garcia S, Martin DO, Lopez AA, Claudi T, König R, White SM, Sawyer SL, Bernstein JA, Slattery L, Jobling RK, Yoon G, Curry CJ, Merrer ML, Luyer BL, Héron D, Mathieu-Dramard M, Bitoun P, Odent S, Amiel J, Kuentz P, Thevenon J, Laville M, Reznik Y, Fagour C, Nunes ML, Delesalle D, Manouvrier S, Lascols O, Huet F, Binquet C, Faivre L, Rivière JB, Vigouroux C, Njølstad PR, Innes AM, Thauvin-Robinet C.
Clinical reappraisal of SHORT syndrome with PIK3R1 mutations: toward recommendation for molecular testing and management. Clin Genet. Article CAS PubMed Google Scholar. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC.
Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man.
Belfiore F, Iannello S, Volpicelli G. Insulin sensitivity indices calculated from basal and OGTT-induced insulin, glucose, and FFA levels. Mol Genet Metab. Lewandowski KC, Płusajska J, Horzelski W, Bieniek E, Lewiński A. Limitations of insulin resistance assessment in polycystic ovary syndrome.
Endocr Connect. Gutch M, Kumar S, Razi SM, Gupta KK, Gupta A. Indian J Endocrinol Metab. Rena G, Hardie DG, Pearson ER. The mechanisms of action of metformin. Li M, Li X, Zhang H, Lu Y. Molecular mechanism of metformin for diabetes and cancer treatment. Front Physiol. Article PubMed PubMed Central Google Scholar.
Metformin: an anti-diabetic drug to fight cancer. Phamacol Res. Thauvin-Robinet C, Auclair M, Duplomb L, Caron-Debarle M, Avila M, St-Onge J, Le Merrer M, Le Luyer B, Héron D, Mathieu-Dramard M, Bitoun P, Petit JM, Odent S, Amiel J, Picot D, Carmignac V, Thevenon J, Callier P, Laville M, Reznik Y, Fagour C, Nunes ML, Capeau J, Lascols O, Huet F, Faivre L, Vigouroux C, Rivière JB.
PIK3R1 mutations cause syndromic insulin resistance with lipoatrophy. Article CAS PubMed PubMed Central Google Scholar. Mutations in PIK3R1 cause SHORT syndrome.
Insulin resistance uncoupled from dyslipidemia due to C-terminal PIK3R1 mutations. JCI Insight. Verge CF, Donaghue KC, Williams PF, Cowell CT, Silink M.
Insulin-resistant diabetes during growth hormone therapy in a child with SHORT syndrome. Acta Paediatr. Download references. Department of Endocrinology and Metabolic Diseases, Medical University of Lodz, Lodz, Poland. Krzysztof C. You can also search for this author in PubMed Google Scholar. KCL lead clinician involved in the care of the patient, preparation of the manuscript.
KD, MB, JK doctors involved in clinical care internal medicine and gynaecology. Preparation of the manuscript, particularly tables and figure. AL overall supervision and review of the manuscript as the Head of the Department.
All authors read and approved the final manuscript. This case was presented as a guided poster at the 54th Annual Meeting of the European Association for the Study of Diabetes The EASD in Berlin, Germany October 1—5, , Session: Monogenic diabetes: ePoster No.
Correspondence to Andrzej Lewiński. Patient consent was obtained to anonymously present results of her investigation for research and education purposes. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Open Access This article is distributed under the terms of the Creative Commons Attribution 4. Reprints and permissions. Lewandowski, K. et al. Metformin paradoxically worsens insulin resistance in SHORT syndrome.
Diabetol Metab Syndr 11 , 81 Download citation. Received : 16 April Accepted : 21 September Published : 01 October Anyone you share the following link with will be able to read this content:. Sorry, a shareable link is not currently available for this article. Provided by the Springer Nature SharedIt content-sharing initiative.
In response to the body's insulin resistance, the pancreas deploys more of the hormone to keep cells energized and manage blood glucose levels in a healthy range. This is why people with type 2 diabetes tend to have higher levels of circulating insulin. The ability of the pancreas to increase insulin production means that insulin resistance alone won't have any symptoms at first.
Over time, though, insulin resistance tends to get worse, and the pancreatic beta cells that make insulin can wear out. Eventually, the pancreas no longer produces enough insulin to overcome the cells' resistance.
The result is higher blood glucose levels, and ultimately prediabetes or type 2 diabetes. Insulin has other roles in the body besides regulating blood glucose levels, and the effects of insulin resistance are thought to go beyond diabetes.
For example, some research has shown that insulin resistance, independent of diabetes, is associated with heart disease. Scientists are beginning to get a better understanding of how insulin resistance develops.
For starters, several genes have been identified that make a person more or less likely to develop the condition. It's also known that older people are more prone to insulin resistance. Lifestyle can play a role, too. Being sedentary, overweight or obese increases the risk for insulin resistance.
It's not clear, but some researchers theorize that extra fat tissue may cause inflammation, physiological stress or other changes in the cells that contribute to insulin resistance.
There may even be some undiscovered factor produced by fat tissue, perhaps a hormone, that signals the body to become insulin resistant. Doctors don't usually test for insulin resistance as a part of standard diabetes care. In clinical research, however, scientists may look specifically at measures of insulin resistance, often to study potential treatments for insulin resistance or type 2 diabetes.
They typically administer a large amount of insulin to a subject while at the same time delivering glucose to the blood to keep levels from dipping too low.
The less glucose needed to maintain normal blood glucose levels, the greater the insulin resistance. Insulin resistance comes in degrees. The more insulin resistant a person with type 2 is, the harder it will be to manage their diabetes because more medication is needed to get enough insulin in the body to achieve target blood glucose levels.
Insulin resistance isn't a cause of type 1 diabetes, but people with type 1 who are insulin resistant will need higher insulin doses to keep their blood glucose under control than those who are more sensitive to insulin. As with type 2, people with type 1 may be genetically predisposed to become insulin resistant, or they may develop resistance due to being overweight.
Cindy T. Pau, Insluin Keefe, Jessica Garcinia cambogia for nail health, Corrine K. Ihsulin metformin is widely used to improve insulin resistance in women with Metformin and insulin sensitivity ovary sensitivitg PCOSits mechanism of action is complex, Metformin and insulin sensitivity inconsistent effects on insulin sensitivity and variability in treatment response. The aim of the study was to delineate the effect of metformin on glucose and insulin parameters, determine additional treatment outcomes, and predict patients with PCOS who will respond to treatment. We conducted an open-label, interventional study at an academic medical center. Interval visits were performed to monitor anthropometric measurements and menstrual cycle parameters.Metformin and exercise independently OMAD recipes glycemic control.
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Inxulin plasma glucose is Metformni by sfnsitivity principally hepatic insulni production, as glucose disposal by skeletal muscle and senssitivity tissue is minimal sensitivitty Following mixed-meal absorption, insulin levels rise in response to carbohydrate and to smaller extents protein to reduce liver glucose production and lipolysis Metfornin well as stimulate blood flow to skeletal muscle for glucose uptake Mstformin, insulin ssensitivity on the Metflrmin to provide sensitigity regulation of endogenous glucose production ajd well as sensitivkty additional food intake Exercise can sensitivify of either aerobic or resistance form, although the combination may result in the best HbA1c reductions 2.
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Exercise and metformin both increase 5-adenosine monophosphate kinase AMPK. This is important because AMPK is one of the several mechanisms by which each therapy act to suppress hepatic glucose output and increase insulin-stimulated glucose disposal 11 As a result, it would be fair to expect a greater benefit to glycemic control since two of the major organs regulating blood glucose would be impacted compared with either treatment alone.
However, the literature on co-prescribing lifestyle modification with metformin on blood glucose is equivocal Table 1. Indeed, some 25 have shown that lifestyle modification plus metformin resulted in more weight loss than lifestyle modification alone, and the weight loss was associated with lower 2-h circulating glucose levels.
This is somewhat consistent with recent work by Erickson et al. Furthermore, Ortega et al. sought to test the effects of combining metformin with exercise on free-living glycemic control in individuals with prediabetes or T2D The results of this later work demonstrated that high intensity interval exercise in combination with metformin therapy lowered interstitial fluid glucose to a greater extent than exercise alone.
Interestingly, others have suggested that in people with T2D treated with metformin that timing exercise 30 to 60 min following drug ingestion may impact plasma glucose and insulin to a greater extent than exercising 90 min after ingestion The Diabetes Aerobic and Resistance Exercise DARE trial, however, showed that people with T2D on metformin plus lifestyle modification had similar HbA1c improvements when compared with individuals on lifestyle modification only This is consistent with the IDDP since it was shown that the combination therapy of metformin and lifestyle modification had equivalent effects to reduce the progression from prediabetes to T2D Notwithstanding this, a retrospective analysis of the Look AHEAD study demonstrated that people with type 2 diabetes treated with metformin prior to and during intensive lifestyle therapy had smaller improvements in fasting plasma glucose and HbA1c compared with those undergoing lifestyle therapy only Further, the work by Boulé et al.
Their results implied that metformin blunted reductions in post-prandial blood glucose concentrations during a standardized meal. Together, most 2627 but not all 2431 studies showing an additive effect of metformin plus exercise studied individuals who were already prescribed metformin.
In contrast, we showed previously 32 that 12 weeks of metformin plus exercise training prospectively in naïve users had no effect on fasting plasma glucose in adults with prediabetes.
This is consistent with newer work 3334 whereby in normoglycemic insulin-resistant adults, fasting or postprandial glucose levels did not appear to be negatively affected by metformin.
Somewhat surprisingly, however, is the observation that no randomized clinical trial has been designed to date to test the effectiveness of exercise plus metformin on glycemic control. Given that some work shows opposing 31additive 2627or null findings 32 — 34it is reasonable to suggest that metformin contributes to inter-individual glycemic response differences Table 1.
Table 1. Summary of clinical trials examining the impact of metformin in combination with exercise on glycemic control compared to exercise alone.
Exercise improves glycemic control through both skeletal muscle insulin-dependent and insulin-independent mechanisms Subsequently, contraction mediated mechanisms favoring glucose uptake last for ~3—6 h following a single bout of exercise.
In time, insulin-sensitizing effects take over to explain improved glucose control Habitual exercise i. Metformin is suggested to stimulate skeletal muscle glucose uptake and oxidation Moreover, metformin has been shown to lower intramuscular triglyceride content and bioactive acyl-chain bioactive lipids 3839 through in part elevations in fat oxidation.
Together, these observations indicate that metformin has effects on skeletal muscle energy metabolism that favor glucose homeostasis.
Because metformin is advised as a first-line pharmacological agent, we conducted a double-blind, randomized control trial to test the effect of exercise training with and without metformin on insulin sensitivity in people with prediabetes For 12 weeks, individuals were randomized to either: placebo, metformin, exercise training with placebo, or exercise training with metformin.
Insulin sensitivity was determined about 28 h post-exercise via the euglycemic-hyperinsulinemic clamp with glucose isotope tracers. Tracers were utilized to determine the effects of metformin on skeletal muscle insulin sensitivity as well as hepatic glucose production. Although to date no follow up studies have been conducted using stable isotopes to understand skeletal muscle insulin-stimulated glucose disposal, recent work has tested the effect of metformin on aerobic or resistance exercise skeletal muscle cellular adaptation 33 The results of these studies collectively show that metformin opposes skeletal muscle mitochondrial adaptations as well as inhibits fat-free mass accretion see below Cell Mechanisms for further discussionwhich were directly correlated with attenuated gains in aerobic fitness as well as strength.
Together, these findings highlight that blunted fitness adaptation may relate to the reduced skeletal muscle insulin sensitivity response. In either case, this smaller gain in insulin sensitivity following the combination of exercise and metformin treatment does not apparently lead to stark blood glucose elevations 2331 Further work is warranted to better understand how the combination of drug-exercise therapies contributes to glycemic control across exercise doses, particularly in people with T2D.
For instance, recent work demonstrated that metformin increased carbohydrate utilization during high intensity interval exercise in insulin resistant adults when compared to exercise alone This may be of clinical relevance since carbohydrate use during exercise was related to insulin sensitivity as measured by the intravenous glucose tolerance test.
The findings of Ortega et al. Whether exercise intensity interacts with metformin to affect skeletal muscle insulin sensitivity in clinical populations remains to be tested to help understand if muscle is the primary driver of glycemic variation responses.
Indeed, people at risk for or with T2D, in particular, have impaired responses to insulin This highlights that the liver becomes insulin resistant and plays roles in both fasting and fed states.
While fasting glucose and insulin may serve as a proxy for hepatic glucose production, and study of hepatokines, liver fat, or liver enzymes 43 may provide indirect estimates of hepatic function, use of stable isotopes along with hyperinsulinemic-clamps represent ideal methodologies to depict the role of the liver on glycemic control.
The exercise impact on hepatic glucose production is generally positive. One to seven days of aerobic exercise has been shown in people with T2D to increase hepatic insulin sensitivity 44 Exercise training studies of ~12 weeks have also demonstrated favorable effects on hepatic insulin sensitivity 46with at least some of the effect being related to improved hepatokines i.
It cannot be ruled out though that discrepancies between short-term training studies may relate to exercise intensity, as higher intensity exercise activates AMPK in hepatocytes As a result, it seems that energy deficit, at least partially, created by exercise is an important mechanism improving hepatic insulin sensitivity.
Metformin improves hepatic insulin sensitivity. The mechanism by which metformin lowers hepatic glucose production is mainly thought to be through activation of AMPK and reduction in gluconeogenic enzymes 49although some suggest antagonism of glucagon may be important In addition, metformin is considered to increase fat oxidation in hepatocytes, thereby reducing the potential delirious effects of lipids on insulin signaling Recent work has suggested that metformin may benefit conditions of hepatic steatosis.
In particular, although metformin-induced similar reductions in the hepatic triglyceride content of Otsuka Long-Evans Tokushima Fatty OLETF rats under caloric restriction, compared to caloric restriction alone, the combined treatment lowered hepatic-derived inflammation more Additionally, metformin augmented the benefits of caloric restriction on lowering post-prandial circulating glucose in rodents, suggesting that metformin may impact the liver during energy deficit reduce diabetes and non-alcoholic fatty liver disease risk This observation of greater glycemic benefit was in parallel to greater beta-oxidation and mitochondrial mitophagy i.
To date, we are aware of only one study in humans that has systematically tested the effect of combining metformin with exercise on hepatic glucose production
: Metformin and insulin sensitivity| Metformin paradoxically worsens insulin resistance in SHORT syndrome | The ihsulin of metformin in the management of NAFLD. Biguanides and NIDDM. Correspondence Protein-packed dishes Sensitiviyy Lewiński. Metformin and insulin sensitivity, metformin treatment might be potentially harmful in these patients. Gloria Queipo-García. Sarabia VLam LBurdett ELeiter LAKlip A. Competing interests The authors declare that they have no competing interests. |
| Introduction | As with any medication, metformin may have potential side effects, and its use should be monitored by a healthcare professional. It is also crucial for individuals taking metformin to adhere to their prescribed treatment plan, including regular blood sugar monitoring and lifestyle modifications. In conclusion, metformin plays a significant role in the management of type 2 diabetes. By reducing liver glucose production, improving insulin sensitivity, and potentially aiding in weight loss, metformin helps individuals with diabetes achieve better glycemic control. However, it is important to remember that diabetes management is multifaceted, and metformin should be used in conjunction with other lifestyle modifications to achieve optimal results. Studies have shown that metformin can effectively improve insulin sensitivity and reduce insulin resistance in individuals with prediabetes or type 2 diabetes. It works by activating an enzyme called AMP-activated protein kinase AMPK , which regulates cellular energy balance. By activating AMPK, metformin promotes glucose uptake in skeletal muscles and decreases glucose production in the liver. Multiple clinical trials have demonstrated the efficacy of metformin in the treatment of insulin resistance. These studies have shown that metformin can significantly improve insulin sensitivity, reduce fasting blood sugar levels, and decrease HbA1c levels, a marker of long-term blood sugar control. Furthermore, metformin has been found to slow the progression from prediabetes to type 2 diabetes. In addition to improving insulin sensitivity, metformin offers other potential benefits for individuals with insulin resistance. It may help lower blood pressure, improve lipid profile by reducing LDL cholesterol and triglyceride levels, and support weight loss. These benefits not only help in managing diabetes but also lower the risk of cardiovascular complications. Like any medication, metformin may cause side effects. Common side effects include gastrointestinal symptoms such as nausea, diarrhea, and stomach discomfort. These side effects are usually mild and resolve over time. Rarely, metformin can lead to lactic acidosis, a serious condition that requires immediate medical attention. It is crucial to discuss any concerns or potential side effects with a healthcare provider. While metformin is a valuable option for managing insulin resistance, lifestyle changes also play a vital role. Regular exercise, a healthy diet that focuses on whole foods, weight management, and stress reduction can improve insulin sensitivity. Understanding the importance of these lifestyle modifications is essential for comprehensive insulin resistance management. In addition to metformin, several other medications may be prescribed to manage insulin resistance in individuals with type 2 diabetes. These include thiazolidinediones, dipeptidyl peptidase-4 DPP-4 inhibitors, and sodium-glucose cotransporter-2 SGLT2 inhibitors. Each medication works differently to target specific aspects of diabetes management. As clinicians and researchers continue to explore the complexities of insulin resistance and its treatments, metformin has emerged as a potential game-changer. It not only improves insulin sensitivity but also offers additional benefits for cardiovascular health and weight management. However, as with any medication, it is essential to consult with a healthcare provider before starting or adjusting metformin therapy. Are you looking for sustainably packaged online prescriptions? Visit Cabinet Health to explore our range of medications and discover eco-friendly solutions for your healthcare needs! Here to help keep your health in mind - medicine that is easy, sustainable and proven safe. Get your Metformin Glucophage refills in stunning personalized bottles with Cabinet Health. Apoorva T, MHM. April 20, Metformin For Type 2 Diabetes - Benefits and Side Effects. Moira Lawler, March 17, , The Possible Benefits of Metformin for Type 2 Diabetes and Other Health Conditions. As a service to our readers, Cabinet Health provides access to our library of archived medical content. Please note the date of last review or update on all articles. No content on this site, regardless of date, should ever be used as a substitute for direct medical advice from your doctor or other qualified clinician. Check out other articles we have on the blog. Low patient medication adherence rates comes with many consequences. In this blog post, we'll explore why medication adherence is vital for maintaining good health and how it can significantly impact overall well-being. Having high blood cholesterol can put you at an increased risk of heart attack and stroke. If your cholesterol or triglyceride levels are high, your provider may suggest lifestyle changes or prescribe medication to help bring these levels down. Embrace the unexpected and discover the extraordinary with each step of your journey. Why is cholesteran an important health topic and what do the numbers in your lipid panel mean? rx system visualized glass jar Article Highlights Insulin resistance is a common condition that affects many individuals, especially those with prediabetes or type 2 diabetes. See If Your Prescriptions Qualify for Free. Try Your Name! Di r ections: A ctual di r ection s will r eflec t you r p r escription onc e t r ans f e r ed. See If Your Prescriptions Qualify for Free Stylish, Plastic-Free, Customized Glass Bottles. Here's How Your 💖Custom Labels Will Look:. See If Yours Qualify. Metformin generic for Glucophage®. Shop Now. Link Moira Lawler, March 17, , The Possible Benefits of Metformin for Type 2 Diabetes and Other Health Conditions. Continue Reading. ON THE BLOG. Taken together with data from the current study, glucose effectiveness, not insulin sensitivity, improves with metformin treatment. The second objective of the study was to determine additional effects of metformin treatment in women with PCOS and to determine factors that predicted improvement. Patients with lower baseline T levels pre-hCG and pre-metformin were more likely to have an ovulatory response supporting previous findings 41 , 44 , 46 , although a distinct cutoff was not apparent. After metformin treatment, the T and androstenedione levels were lower in women who ovulated compared to those who did not. Previous studies suggest that higher insulin levels, insulin resistance, and less severe menstrual abnormalities were predictors of an ovulatory response A meta-analysis suggested no effect of weight In the current study, improved ovulation had no relationship to weight, initial menstrual cycle frequency, FSH or LH levels, insulin levels or insulin resistance, ovarian volume, or follicle number. There was also no relationship between ovulation and increased glucose effectiveness, nor was ovulation predicted by glucose tolerance M in previous studies The data support the concept that metformin has a direct ovarian effect on androgen levels that is not mediated through changes in gonadotropin or insulin levels. Taken together, it is possible that metformin induces ovulation by directly decreasing steroidogenesis, thereby reducing the inhibitory effects of androgens on folliculogenesis. In addition to lower T levels after metformin treatment in women who ovulated, T levels decreased overall. Women with the highest initial T levels had the most significant reductions. The T response to metformin has been variable in previous work 17 , 18 , 44 , 46 — 50 , with lean women exhibiting a greater decrease 14 , Nevertheless, there was no relationship between BMI and response to metformin in the current study, requiring further examination of BMI as a predictive factor. The improvement in T level was also unrelated to changes in glucose levels or effectiveness and insulin or LH levels. The mechanism explaining the ability of metformin to lower androgen levels may also be elucidated through further understanding of mitochondrial complex I. Metformin has been reported to decrease androgen levels in human theca cell cultures 51 , Indirect examinations have demonstrated a decrease in ovarian Pc17α activity after metformin treatment Recent studies demonstrate a reduction in both CYP17A1-lyase and 3β-hydroxysteroid dehydrogenase II 3βHSDII activity when assessed in adrenal cells, which appears to be mediated through inhibition of mitochondrial complex I of the respiratory chain Other parameters that improved after metformin treatment include weight, hip circumference, diastolic blood pressure, total cholesterol, and low-density lipoprotein. Weight loss has been demonstrated in other studies of metformin treatment The DEXA measurements in the current study suggest that it is not fat or bone mineral mass that decreases with metformin treatment. Although the decrease may represent lean mass, previous studies suggest that metformin protects or increases lean mass in aging men and in adolescent girls 54 , Therefore, further studies are needed to determine the reason for the change in body weight and composition. Systolic and diastolic blood pressure decreased with metformin in other studies as well Previous studies have demonstrated that metformin improved lipid profiles with increased HDL in women with PCOS 44 and decreased triglyceride levels in subjects with type 2 diabetes 15 , without improvements in cholesterol levels HDL and triglycerides did not improve in the current study, which may relate to lower baseline triglyceride and HDL levels in this study compared to others as well as differences in the study population and metformin dosing. None of these parameters were associated with improvement in glucose effectiveness. There are limitations to the study. It is not a randomized, placebo-controlled trial. Menstrual cycles were monitored by history and prospectively between the screening visit and the first study visit. Therefore, anovulatory bleeding could be misinterpreted as ovulatory, resulting in a conservative estimate of improved ovulatory frequency. The treatment period is relatively short. Although the effects of metformin can be rapid 56 , a more pronounced ovulatory response may have been demonstrated if the treatment duration were extended to 6 months 45 , Finally, the study did not test mitochondrial complex 1 function directly, and it is possible that the mechanism of glucose and T reduction may occur through alternate or tissue-specific mechanisms. This study challenges the rationale of using metformin in subjects with PCOS to improve insulin sensitivity. Metformin improved fasting glucose and glucose effectiveness. It also improved T levels and ovulation in association with lower T levels. However, the improved glucose effectiveness and T levels were not associated with each other. Taken together with evidence that metformin lowers intracellular ATP in hepatocytes, muscle, and adrenal cells, the data point to a coordinated mechanism of metformin action related to its ability to inhibit mitochondrial complex I. Improvement in glucose effectiveness and androgen levels must be examined as separate outcome parameters in women with PCOS on metformin treatment. Importantly, further investigation to delineate the exact site and mechanism of action of metformin on mitochondrial complex I may help explain the variability in treatment response and provide insight into new therapeutic targets for the treatment of PCOS. This work was supported by American Diabetes Association Grant CT to C. Disclosure Summary: C. have nothing to declare. has consulted for Astra Zeneca. Knochenhauer ES , Key TJ , Kahsar-Miller M , Waggoner W , Boots LR , Azziz R. Prevalence of the polycystic ovary syndrome in unselected black and white women of the southeastern United States: a prospective study. J Clin Endocrinol Metab. Google Scholar. Diamanti-Kandarakis E , Kouli CR , Bergiele AT , et al. A survey of the polycystic ovary syndrome in the Greek island of Lesbos: hormonal and metabolic profile. Asunción M , Calvo RM , San Millán JL , Sancho J , Avila S , Escobar-Morreale HF. A prospective study of the prevalence of the polycystic ovary syndrome in unselected Caucasian women from Spain. Dunaif A , Segal KR , Futterweit W , Dobrjansky A. Profound peripheral insulin resistance, independent of obesity, in polycystic ovary syndrome. Chang RJ , Nakamura RM , Judd HL , Kaplan SA. Insulin resistance in nonobese patients with polycystic ovarian disease. Ehrmann DA , Sturis J , Byrne MM , Karrison T , Rosenfield RL , Polonsky KS. Insulin secretory defects in polycystic ovary syndrome. Relationship to insulin sensitivity and family history of non-insulin-dependent diabetes mellitus. J Clin Invest. Ehrmann DA , Barnes RB , Rosenfield RL , Cavaghan MK , Imperial J. Prevalence of impaired glucose tolerance and diabetes in women with polycystic ovary syndrome. Diabetes Care. Legro RS , Kunselman AR , Dodson WC , Dunaif A. Prevalence and predictors of risk for type 2 diabetes mellitus and impaired glucose tolerance in polycystic ovary syndrome: a prospective, controlled study in affected women. Welt CK , Arason G , Gudmundsson JA , et al. Defining constant versus variable phenotypic features of women with polycystic ovary syndrome using different ethnic groups and populations. Apridonidze T , Essah PA , Iuorno MJ , Nestler JE. Prevalence and characteristics of the metabolic syndrome in women with polycystic ovary syndrome. Ehrmann DA , Liljenquist DR , Kasza K , Azziz R , Legro RS , Ghazzi MN. Prevalence and predictors of the metabolic syndrome in women with polycystic ovary syndrome. Nestler JE , Jakubowicz DJ. Decreases in ovarian cytochrome Pc17α activity and serum free testosterone after reduction of insulin secretion in polycystic ovary syndrome. N Engl J Med. Nestler JE , Jakubowicz DJ , Evans WS , Pasquali R. Effects of metformin on spontaneous and clomiphene-induced ovulation in the polycystic ovary syndrome. Tang T , Lord JM , Norman RJ , Yasmin E , Balen AH. Insulin-sensitising drugs metformin, rosiglitazone, pioglitazone, D-chiro-inositol for women with polycystic ovary syndrome, oligo amenorrhoea and subfertility [published online May 16, ]. Cochrane Database Syst Rev. doi: DeFronzo RA , Barzilai N , Simonson DC. Mechanism of metformin action in obese and lean noninsulin-dependent diabetic subjects. Yu JG , Kruszynska YT , Mulford MI , Olefsky JM. A comparison of troglitazone and metformin on insulin requirements in euglycemic intensively insulin-treated type 2 diabetic patients. Ehrmann DA , Cavaghan MK , Imperial J , Sturis J , Rosenfield RL , Polonsky KS. Effects of metformin on insulin secretion, insulin action, and ovarian steroidogenesis in women with polycystic ovary syndrome. Diamanti-Kandarakis E , Kouli C , Tsianateli T , Bergiele A. Therapeutic effects of metformin on insulin resistance and hyperandrogenism in polycystic ovary syndrome. Eur J Endocrinol. Zawadzki JK , Dunaif A. Diagnostic criteria for polycystic ovary syndrome: towards a rational approach. In: Dunaif A , Givens JR , Haseltine FP , Merriam GR , eds. Polycystic Ovary Syndrome. Boston, MA : Blackwell Scientific ; : — Google Preview. Taylor AE , McCourt B , Martin KA , et al. Determinants of abnormal gonadotropin secretion in clinically defined women with polycystic ovary syndrome. Azziz R , Hincapie LA , Knochenhauer ES , Dewailly D , Fox L , Boots LR. Screening for hydroxylase-deficient nonclassic adrenal hyperplasia among hyperandrogenic women: a prospective study. Fertil Steril. Welch S , Gebhart SS , Bergman RN , Phillips LS. Minimal model analysis of intravenous glucose tolerance test-derived insulin sensitivity in diabetic subjects. Welt CK , Adams JM , Sluss PM , Hall JE. Inhibin A and inhibin B responses to gonadotropin withdrawal depends on stage of follicle development. Pacini G , Bergman RN. MINMOD: a computer program to calculate insulin sensitivity and pancreatic responsivity from the frequently sampled intravenous glucose tolerance test. Comput Methods Programs Biomed. Miller RA , Birnbaum MJ. An energetic tale of AMPK-independent effects of metformin. Jackson RA , Hawa MI , Jaspan JB , et al. Mechanism of metformin action in non-insulin-dependent diabetes. Nosadini R , Avogaro A , Trevisan R , et al. Effect of metformin on insulin-stimulated glucose turnover and insulin binding to receptors in type II diabetes. Owen MR , Doran E , Halestrap AP. Evidence that metformin exerts its anti-diabetic effects through inhibition of complex 1 of the mitochondrial respiratory chain. Biochem J. El-Mir MY , Nogueira V , Fontaine E , Avéret N , Rigoulet M , Leverve X. Dimethylbiguanide inhibits cell respiration via an indirect effect targeted on the respiratory chain complex I. J Biol Chem. Miller RA , Chu Q , Xie J , Foretz M , Viollet B , Birnbaum MJ. Biguanides suppress hepatic glucagon signalling by decreasing production of cyclic AMP. Bergman RN. Lilly Lecture Toward physiological understanding of glucose tolerance. Minimal-model approach. Kahn BB , Alquier T , Carling D , Hardie DG. AMP-activated protein kinase: ancient energy gauge provides clues to modern understanding of metabolism. Cell Metab. Foretz M , Hébrard S , Leclerc J , et al. Hardie DG , Carling D , Carlson M. Annu Rev Biochem. Musi N , Hirshman MF , Nygren J , et al. Metformin increases AMP-activated protein kinase activity in skeletal muscle of subjects with type 2 diabetes. Zierath JR , Galuska D , Nolte LA , Thörne A , Kristensen JS , Wallberg-Henriksson H. Effects of glycaemia on glucose transport in isolated skeletal muscle from patients with NIDDM: in vitro reversal of muscular insulin resistance. Sarabia V , Lam L , Burdett E , Leiter LA , Klip A. Glucose transport in human skeletal muscle cells in culture. Stimulation by insulin and metformin. Brunzell JD , Robertson RP , Lerner RL , et al. Relationships between fasting plasma glucose levels and insulin secretion during intravenous glucose tolerance tests. Savage PJ , Bennion LJ , Flock EV , et al. Diet-induced improvement of abnormalities in insulin and glucagon secretion and in insulin receptor binding in diabetes mellitus. Açbay O , Gündodu S. Can metformin reduce insulin resistance in polycystic ovary syndrome? Palomba S , Falbo A , Russo T , et al. Insulin sensitivity after metformin suspension in normal-weight women with polycystic ovary syndrome. Bergman RN , Finegood DT , Ader M. Assessment of insulin sensitivity in vivo. Endocr Rev. DeFronzo RA , Tobin JD , Andres R. Glucose clamp technique: a method for quantifying insulin secretion and resistance. Am J Physiol. Moghetti P , Castello R , Negri C , et al. Metformin effects on clinical features, endocrine and metabolic profiles, and insulin sensitivity in polycystic ovary syndrome: a randomized, double-blind, placebo-controlled 6-month trial, followed by open, long-term clinical evaluation. Essah PA , Apridonidze T , Iuorno MJ , Nestler JE. Effects of short-term and long-term metformin treatment on menstrual cyclicity in women with polycystic ovary syndrome. Fleming R , Hopkinson ZE , Wallace AM , Greer IA , Sattar N. Ovarian function and metabolic factors in women with oligomenorrhea treated with metformin in a randomized double blind placebo-controlled trial. Lean women with polycystic ovary syndrome respond to insulin reduction with decreases in ovarian Pc17 α activity and serum androgens. Legro RS , Barnhart HX , Schlaff WD , et al. Clomiphene, metformin, or both for infertility in the polycystic ovary syndrome. Maciel GA , Soares Júnior JM , Alves da Motta EL , Abi Haidar M , de Lima GR , Baracat EC. Nonobese women with polycystic ovary syndrome respond better than obese women to treatment with metformin. Baillargeon JP , Jakubowicz DJ , Iuorno MJ , Jakubowicz S , Nestler JE. Effects of metformin and rosiglitazone, alone and in combination, in nonobese women with polycystic ovary syndrome and normal indices of insulin sensitivity. Mansfield R , Galea R , Brincat M , Hole D , Mason H. Metformin has direct effects on human ovarian steroidogenesis. Attia GR , Rainey WE , Carr BR. Metformin directly inhibits androgen production in human thecal cells. Hirsch A , Hahn D , Kempná P , et al. Metformin inhibits human androgen production by regulating steroidogenic enzymes HSD3B2 and CYP17A1 and complex I activity of the respiratory chain. Rodríguez-Moctezuma JR , Robles-López G , López-Carmona JM , Gutiérrez-Rosas MJ. Effects of metformin on the body composition in subjects with risk factors for type 2 diabetes. Diabetes Obes Metab. Lee CG , Boyko EJ , Barrett-Connor E , et al. Insulin sensitizers may attenuate lean mass loss in older men with diabetes. la Marca A , Egbe TO , Morgante G , et al. Metformin treatment reduces ovarian cytochrome Pc17α response to human chorionic gonadotrophin in women with insulin resistance-related polycystic ovary syndrome. Hum Reprod. Oxford University Press is a department of the University of Oxford. It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide. Sign In or Create an Account. Endocrine Society Journals. Advanced Search. Search Menu. Article Navigation. 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| PCOS: Insulin and Metformin – Center for Young Women's Health | Belfiore F, Iannello S, Volpicelli G. Insulin sensitivity indices calculated from basal and OGTT-induced insulin, glucose, and FFA levels. Mol Genet Metab. Lewandowski KC, Płusajska J, Horzelski W, Bieniek E, Lewiński A. Limitations of insulin resistance assessment in polycystic ovary syndrome. Endocr Connect. Gutch M, Kumar S, Razi SM, Gupta KK, Gupta A. Indian J Endocrinol Metab. Rena G, Hardie DG, Pearson ER. The mechanisms of action of metformin. Li M, Li X, Zhang H, Lu Y. Molecular mechanism of metformin for diabetes and cancer treatment. Front Physiol. Article PubMed PubMed Central Google Scholar. Metformin: an anti-diabetic drug to fight cancer. Phamacol Res. Thauvin-Robinet C, Auclair M, Duplomb L, Caron-Debarle M, Avila M, St-Onge J, Le Merrer M, Le Luyer B, Héron D, Mathieu-Dramard M, Bitoun P, Petit JM, Odent S, Amiel J, Picot D, Carmignac V, Thevenon J, Callier P, Laville M, Reznik Y, Fagour C, Nunes ML, Capeau J, Lascols O, Huet F, Faivre L, Vigouroux C, Rivière JB. PIK3R1 mutations cause syndromic insulin resistance with lipoatrophy. Article CAS PubMed PubMed Central Google Scholar. Mutations in PIK3R1 cause SHORT syndrome. Insulin resistance uncoupled from dyslipidemia due to C-terminal PIK3R1 mutations. JCI Insight. Verge CF, Donaghue KC, Williams PF, Cowell CT, Silink M. Insulin-resistant diabetes during growth hormone therapy in a child with SHORT syndrome. Acta Paediatr. Download references. Department of Endocrinology and Metabolic Diseases, Medical University of Lodz, Lodz, Poland. Krzysztof C. You can also search for this author in PubMed Google Scholar. KCL lead clinician involved in the care of the patient, preparation of the manuscript. KD, MB, JK doctors involved in clinical care internal medicine and gynaecology. Preparation of the manuscript, particularly tables and figure. AL overall supervision and review of the manuscript as the Head of the Department. All authors read and approved the final manuscript. This case was presented as a guided poster at the 54th Annual Meeting of the European Association for the Study of Diabetes The EASD in Berlin, Germany October 1—5, , Session: Monogenic diabetes: ePoster No. Correspondence to Andrzej Lewiński. Patient consent was obtained to anonymously present results of her investigation for research and education purposes. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Open Access This article is distributed under the terms of the Creative Commons Attribution 4. Reprints and permissions. Lewandowski, K. et al. Metformin paradoxically worsens insulin resistance in SHORT syndrome. Diabetol Metab Syndr 11 , 81 Download citation. Received : 16 April Accepted : 21 September Published : 01 October Anyone you share the following link with will be able to read this content:. Sorry, a shareable link is not currently available for this article. Provided by the Springer Nature SharedIt content-sharing initiative. Skip to main content. Search all BMC articles Search. Download PDF. Short report Open access Published: 01 October Metformin paradoxically worsens insulin resistance in SHORT syndrome Krzysztof C. Abstract Background SHORT syndrome is an autosomal dominant condition associated severe insulin resistance IR and lipoatrophy due to post-receptor defect in insulin signaling involving phosphoinositidekinase regulatory subunit 1 PIK3R1 , where no clear treatment guidelines are available. Methods We attempted to test the efficacy metformin in a female patient with SHORT syndrome by measuring glucose and insulin during an extended Oral Glucose Tolerance Test OGTT in a year old patient BMI Results She had lipid concentrations within the reference range, normal thyroid function tests, prolactin, gonadotropins, estradiol and androgens with Free Androgen Index 4. Conclusions Metformin treatment may paradoxically lead to deterioration of insulin resistance and to development of glucose intolerance in SHORT syndrome. Background SHORT syndrome is an autosomal dominant condition associated with severe insulin resistance and early onset of type 2 diabetes in the absence of obesity. Case description We describe a case of year old female patient who presented for an endocrine assessment in our Department with a history of amenorrhoea. Investigation results Her height was cm, weight Table 1 Biochemical and hormonal results of 21 year old women with SHORT syndrome Full size table. Full size image. Discussion Our patient demonstrated typical features of the SHORT syndrome, with severe insulin resistance and lipoatrophy in the absence of dyslipidaemia, as described before [ 1 ]. Conclusions The case of our patient therefore constitutes a caution for clinicians, who treat insulin-resistant states, where metformin is usually a drug of the first choice. Abbreviations IR: insulin resistance PIK3R1: phosphoinositidekinase regulatory subunit 1 OGTT: Oral Glucose Tolerance Test HOMA-IR: Homeostatic Model Assessment of Insulin Resistance TSH: thyroid-stimulating hormone T4: thyroxine SHGB: sex hormone binding globulin DHEAS: dehydroepiandrosterone sulphate PTH: parathyroid hormone ATP: adenosine triphosphate AMP: adenosine monophosphate. References Chudasama KK, Winnay J, Johansson S, Claudi T, König R, Haldorsen I, Johansson B, Woo JR, Aarskog D, Sagen JV, Kahn CR, Molven A, Njølstad PR. Article CAS Google Scholar Innes AM, Dyment DA. PubMed Google Scholar Avila M, Dyment DA, Sagen JV, St-Onge J, Moog U, Chung BHY, Mo S, Mansour S, Albanese A, Garcia S, Martin DO, Lopez AA, Claudi T, König R, White SM, Sawyer SL, Bernstein JA, Slattery L, Jobling RK, Yoon G, Curry CJ, Merrer ML, Luyer BL, Héron D, Mathieu-Dramard M, Bitoun P, Odent S, Amiel J, Kuentz P, Thevenon J, Laville M, Reznik Y, Fagour C, Nunes ML, Delesalle D, Manouvrier S, Lascols O, Huet F, Binquet C, Faivre L, Rivière JB, Vigouroux C, Njølstad PR, Innes AM, Thauvin-Robinet C. Article CAS PubMed Google Scholar Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Article CAS Google Scholar Belfiore F, Iannello S, Volpicelli G. Article CAS Google Scholar Lewandowski KC, Płusajska J, Horzelski W, Bieniek E, Lewiński A. Article CAS Google Scholar Gutch M, Kumar S, Razi SM, Gupta KK, Gupta A. Article CAS Google Scholar Rena G, Hardie DG, Pearson ER. Article CAS Google Scholar Li M, Li X, Zhang H, Lu Y. Article CAS Google Scholar Thauvin-Robinet C, Auclair M, Duplomb L, Caron-Debarle M, Avila M, St-Onge J, Le Merrer M, Le Luyer B, Héron D, Mathieu-Dramard M, Bitoun P, Petit JM, Odent S, Amiel J, Picot D, Carmignac V, Thevenon J, Callier P, Laville M, Reznik Y, Fagour C, Nunes ML, Capeau J, Lascols O, Huet F, Faivre L, Vigouroux C, Rivière JB. Article PubMed PubMed Central Google Scholar Verge CF, Donaghue KC, Williams PF, Cowell CT, Silink M. Article CAS Google Scholar Download references. Author information Authors and Affiliations Department of Endocrinology and Metabolic Diseases, Medical University of Lodz, Lodz, Poland Krzysztof C. Lewandowski View author publications. View author publications. Consent for publication Not applicable. Competing interests The authors declare that they have no competing interests. Additional information Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Rights and permissions Open Access This article is distributed under the terms of the Creative Commons Attribution 4. Preclinical studies in rodents demonstrated that metformin acts by inhibiting endogenous glucose production by limiting the use of glucose precursors for gluconeogenesis. Another preclinical study reported that metformin acts by inhibiting glucagon-induced hepatic glucose production. All of these studies involve rodent models with either suprapharmacological doses of metformin or other biguanides, or injected metformin directly in to peritoneum. Results of a study performed at Mayo Clinic to determine whether these rodent experiments can be translated into humans was published in Cell Reports in Nair explains: "This study was a double-blind, placebo-controlled, randomized crossover design in patients with prediabetes to determine the effect of two weeks of metformin administration. The study confirmed that metformin increases glucose tolerance and insulin sensitivity, but it also increases plasma glucagon levels, not only in the fasted state in some study participants, but also following a meal, which seemed to prevent hypoglycemia. During metformin therapy, increased glucagon levels prevented a fall in endogenous glucose production, thus providing a valid explanation for why metformin administration usually is not associated with hypoglycemia. Additionally, we found that gluconeogenesis precursors were reduced by metformin as opposed to reduced utilization of glucose precursors unlike as reported in rodent models. Metformin also counteracted some of glucagon's catabolic effects, such as increased energy expenditure and protein catabolism. Maintenance of normal blood glucose concentrations in individuals with prediabetes during treatment with metformin. This study thus offered insight into the effects of metformin in individuals with prediabetes. While extrapolating this information to patients with T2DM may need further clinical studies, it is likely that lack of hypoglycemia in patients with T2DM treated with metformin is explained by enhanced hepatic glucose production due to increased glucagon secretion. The study also shows that metformin reduces insulin secretion, which may reflect lesser need of insulin since insulin sensitivity is enhanced by metformin. Konopka AR, et al. Hyperglucagonemia mitigates the effect of metformin on glucose production in prediabetes. Cell Reports. This content does not have an English version. This content does not have an Arabic version. Metformin revisited. April 11, Chemical structure for metformin Enlarge image Close. Chemical structure for metformin Chemical structure for metformin 1,1-dimethylbiguanide; C4H11N5. Maintenance of normal blood glucose concentrations Enlarge image Close. Maintenance of normal blood glucose concentrations Maintenance of normal blood glucose concentrations in individuals with prediabetes during treatment with metformin. Related Content. An emerging connection between circadian rhythm disruption and type 2 diabetes mellitus. Medical Professionals Metformin revisited. Show the heart some love! Give Today. Help us advance cardiovascular medicine. Find a doctor. Explore careers. Sign up for free e-newsletters. About Mayo Clinic. About this Site. Contact Us. Health Information Policy. Media Requests. News Network. Price Transparency. Medical Professionals. Clinical Trials. |
| Understanding Insulin Resistance | It works by activating an enzyme called AMP-activated protein kinase AMPK , which regulates cellular energy balance. Aging Cell. In the metformin group an increase in fat-free mass in accordance with their increase in height over 18 months was found, without an increase in fat mass, resulting in a stable BMI. Short-term aerobic exercise training in obese humans with type 2 diabetes mellitus improves whole-body insulin sensitivity through gains in peripheral, not hepatic insulin sensitivity. Treatment with dietary trans 10 cis 12 conjugated linoleic acid causes isomer-specific insulin resistance in obese men with the metabolic syndrome. |
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