The Authors provide a thorough examination of a wide series of items related to AI in DR screening, including medico-legal issues, still under way of definition worldwide. Most articles strengthen reliability data, mainly useful to diabetologists facing DR screening, being provided with a suggestion (usually green or red flags) by the AI system. In my opinion, the workflow following a red flag has to be well-specified yet: some systems correctly suggest that red flagged patients follow a preferred pathway for a human examination, but the term "preferred" may vary owing to local organisational issues, mainly in LMICs. In my opinion and experience, one must keep in mind that red flags don't inform about how impending a vision loss can be: sometimes, bleeding of a correctly recognized proliferation, or reaching the fovea by correctly identified fluid and exudates approaching it, is a matter of hours. In such cases, missing the need for speed can worsen patients' sight and raise not-yet-defined medico-legal issues. So, I believe it would be safe to obtain an immediate ophthalmologist's or trained diabetologist's examination of all red-flagged images, what is nowadays made really easy by telemedicine.
Dear Editor
This indeed a very good article on emerging class of antidiabetic drugs i.e SGLT2 inhibitors. SGLT2 inhibitors are making their way not only for their role as an adjuvant therapy for control of diabetes, but their beneficial role in providing cardiac safety, renal protection and weight reduction are making these drugs superior in comparison to DPP4 inhibitors, which are another widely used and well tolerated anti diabetic drugs. SGLT2 inhibitors are known to lower blood glucose by inhibiting glucose and sodium re absorption and promoting glycosuria, as a consequence they cause glucose and HbA1C reduction and lowering of blood pressure1. A part from these benefits , SGLT2 inhibitors might acquire potential indication to be used for prevention and treatment of gout due to their uric acid reducing properties2.
Since these drugs got FDA approval and become available, the side effect profile of these drugs have always remained talk of major debates. Well known side effects are genital infection, increase incidence of mycotic infections and diabetic ketoacidosis. One of the major and serious concern with use of SGLT2 inhibitors is possibility of Fournier’s gangrene. Fournier’s gangrene is an extremely rare but life-threatening bacterial infection of the genital tissue. Current article is also reflection of my own experience. I have been prescribing SGLT2 inhibitors quite frequently and most of the patients are in regular follow up and I have not seen any...
Dear Editor
This indeed a very good article on emerging class of antidiabetic drugs i.e SGLT2 inhibitors. SGLT2 inhibitors are making their way not only for their role as an adjuvant therapy for control of diabetes, but their beneficial role in providing cardiac safety, renal protection and weight reduction are making these drugs superior in comparison to DPP4 inhibitors, which are another widely used and well tolerated anti diabetic drugs. SGLT2 inhibitors are known to lower blood glucose by inhibiting glucose and sodium re absorption and promoting glycosuria, as a consequence they cause glucose and HbA1C reduction and lowering of blood pressure1. A part from these benefits , SGLT2 inhibitors might acquire potential indication to be used for prevention and treatment of gout due to their uric acid reducing properties2.
Since these drugs got FDA approval and become available, the side effect profile of these drugs have always remained talk of major debates. Well known side effects are genital infection, increase incidence of mycotic infections and diabetic ketoacidosis. One of the major and serious concern with use of SGLT2 inhibitors is possibility of Fournier’s gangrene. Fournier’s gangrene is an extremely rare but life-threatening bacterial infection of the genital tissue. Current article is also reflection of my own experience. I have been prescribing SGLT2 inhibitors quite frequently and most of the patients are in regular follow up and I have not seen any patient coming up with necrotizing infection of perineum. Therefore considering the diverse beneficial effects associated with this class of drug, it should be considered wherever required.
References:
Pereira, M.J., Eriksson, J.W. Emerging Role of SGLT-2 Inhibitors for the Treatment of Obesity. Drugs 79, 219–230 (2019) doi:10.1007/s40265-019-1057-0
Bailey, CJ. Uric acid and the cardio‐renal effects of SGLT2 inhibitors. Diabetes Obes Metab. 2019; 21: 1291– 1298. https://doi.org/10.1111/dom.13670
We thank the authors for their question and interest in our article. The two cited articles (1,2) are very interesting but differ from what we wanted to show with the St. Carlos GDM Prevention Study (3). The first one is a case-control study analyzing associations of DASH and Mediterranean diets with GDM (1). The second one evaluates the effect of a nutritional intervention with a Mediterranean diet on postpartum development of glucose disorders in women with prior GDM (2). The St. Carlos GDM Prevention Study was a randomized controlled trial that analyzed the effect a nutritional intervention with a MedDiet, supplemented with extra virgin olive oil and nuts, on GDM development.
The motive women were given extra virgin olive oil was to ensure a high compliance with the MedDiet. Not only women increased their intake in these two foods, but also increased their overall MEDAS score (3). This also seemed to translate in a substitution of unhealthy foods for healthy ones. For example, a substitution of unhealthy snacks for nuts and of processed sauces and dressings for olive oil and olive oil-based sauces. The ultimate message we were hoping to convey is that extra virgin olive oil and nuts should be consumed more, with less restrictions. Current Spanish guidelines advise a controlled consumption of these foods in pregnancy.
The type of medical nutrition therapy used in GDM treatment is not standardized and can be different between centers. Due to the results found...
We thank the authors for their question and interest in our article. The two cited articles (1,2) are very interesting but differ from what we wanted to show with the St. Carlos GDM Prevention Study (3). The first one is a case-control study analyzing associations of DASH and Mediterranean diets with GDM (1). The second one evaluates the effect of a nutritional intervention with a Mediterranean diet on postpartum development of glucose disorders in women with prior GDM (2). The St. Carlos GDM Prevention Study was a randomized controlled trial that analyzed the effect a nutritional intervention with a MedDiet, supplemented with extra virgin olive oil and nuts, on GDM development.
The motive women were given extra virgin olive oil was to ensure a high compliance with the MedDiet. Not only women increased their intake in these two foods, but also increased their overall MEDAS score (3). This also seemed to translate in a substitution of unhealthy foods for healthy ones. For example, a substitution of unhealthy snacks for nuts and of processed sauces and dressings for olive oil and olive oil-based sauces. The ultimate message we were hoping to convey is that extra virgin olive oil and nuts should be consumed more, with less restrictions. Current Spanish guidelines advise a controlled consumption of these foods in pregnancy.
The type of medical nutrition therapy used in GDM treatment is not standardized and can be different between centers. Due to the results found in our study, we think that a MedDiet-based medical nutrition therapy can be appropriate for GDM treatment (4). To improve the adherence to this diet, it is very important to recommend increasing the intake of extra virgin olive oil and nuts.
In view of the foregoing, we do think that it might be worthy considering a modification of both the nutrition and pregnancy guidelines and medical nutrition therapy in GDM treatment.
1. Izadi V, Tehrani H, Haghighatdoost F, et.al. Adherence to the DASH and Mediterranean diets is associated with decreased risk for gestational diabetes mellitus. Nutrition 2016;32:1092-6. doi:10.1016/j.nut.2016.03.006.
2. Perez-Ferre N, Valle LD, Torrej MJ, et.al. Diabetes Mellitus and Abnormal Glucose Tolerance Development After Gestational Diabetes: A Three-year, Prospective, Randomized, Clinical based, Mediterranean lifestyle Interventional Study with Parallel Groups. Clinical Nutrition 2015;34:579-585. doi:10.1016/j.clnu.2014.09.005.
3. Assaf-Balut C, García de la Torre N, Durán, A, et al. A Mediterranean diet with additional extra virgin olive oil and pistachios reduces the incidence of gestational diabetes mellitus (GDM): A randomized controlled trial: The St. Carlos GDM prevention study. PLoS One. 2017;12:e0185873. doi:10.1371/journal.pone.0185873.
4. Assaf-Balut C, García de la Torre N, Durán, A, Medical nutrition therapy for gestational diabetes mellitus based on Mediterranean Diet principles: a subanalysis of the St Carlos GDM Prevention Study. BMJ Open Diabetes Res Care.2018. 11;6:e000550. doi: 10.1136/bmjdrc-2018-000550.
As author of the Diabetes Health Profile, I felt that overall the paper provided a generally balanced report of your study, I have however, a number of issues regarding your report.
First, although resulting in a high alpha coefficient (0.79), it is incorrect to calculate an alpha score for the total number of items when the scale itself is multidimensional (Oranges and apples). In doing so, it can result in an overall low alpha score. In this case it is fortunate that the value was high. Had this been a low score this would have been perceived as a negative result to the less knowledgeable.
Secondly, with regard to responsiveness to change, a crude method for measuring change in score was used together with a very limited patient sample. Although the limitation of the methodology was discussed to some extent in the discussion, it would have been preferable at least to measure at both pre and post for each of the three scale domains. Minimally Important Difference (MID) values are available for the DHP that would enable the smallest change in score that is clinically significant to be measured.
Thirdly, in the section ‘Significance of the study’ it would have been more appropriate that the final comment on implementation in clinical practice and studies should have been limited to the ‘Norwegian’ version of the DHP-18. As currently phrased this is rather general and suggests the use of the DHP-18 in clinical studies per se.
As author of the Diabetes Health Profile, I felt that overall the paper provided a generally balanced report of your study, I have however, a number of issues regarding your report.
First, although resulting in a high alpha coefficient (0.79), it is incorrect to calculate an alpha score for the total number of items when the scale itself is multidimensional (Oranges and apples). In doing so, it can result in an overall low alpha score. In this case it is fortunate that the value was high. Had this been a low score this would have been perceived as a negative result to the less knowledgeable.
Secondly, with regard to responsiveness to change, a crude method for measuring change in score was used together with a very limited patient sample. Although the limitation of the methodology was discussed to some extent in the discussion, it would have been preferable at least to measure at both pre and post for each of the three scale domains. Minimally Important Difference (MID) values are available for the DHP that would enable the smallest change in score that is clinically significant to be measured.
Thirdly, in the section ‘Significance of the study’ it would have been more appropriate that the final comment on implementation in clinical practice and studies should have been limited to the ‘Norwegian’ version of the DHP-18. As currently phrased this is rather general and suggests the use of the DHP-18 in clinical studies per se.
Finally, permission to use the DHP-18 was given by Oxford University Innovation, not Dr David Churchman.
T2DM first problem still open is to recognize diabetics so far without proper diagnosis, in order to avoid the series of complications that arise decades before the clinical diabetic symptomatology decades before the clinical diabetic symptomatologyFDA Commissioner Scott Gottlieb, MD, said: "Diabetes affects nearly 30 million Americans. Access to affordable insulin is literally a matter of life and death". Aurobindo would say this is a true and false statement. Why do we all, including FDA, not radically solve the real problem underlying the diabetic growing epidemic? Let's start talking about Pre-Primary and Primary Prevention of T2DM, based on Diabetic and Dislipidemic-Dependent, Inherited Real Risk, bedside diagnosed from birth with a stethoscope, and removed by inexpensive Reconstructing Mitochodrial Quantum Therapy. The till now open problem in the traditional Accademic Medicine is the clinical diagnosis of T2DM from the First of its Five Stages. Well. Recently, a new and original reliable clinical method for diagnosing DM has been added to a flurry of methods that have existed for twenty years. The Corpus Callosum is the part of the brainthat allows communication between its two hemispheres. It is responsible for transmitting neural messages between both the right and left hemispheres. According to Angiobiopathy Theory, microvessel dynamic parallels the related parenchima cell activity. As a consequence,thanks to Quantum Biophysical Semeiotic, physi...
T2DM first problem still open is to recognize diabetics so far without proper diagnosis, in order to avoid the series of complications that arise decades before the clinical diabetic symptomatology decades before the clinical diabetic symptomatologyFDA Commissioner Scott Gottlieb, MD, said: "Diabetes affects nearly 30 million Americans. Access to affordable insulin is literally a matter of life and death". Aurobindo would say this is a true and false statement. Why do we all, including FDA, not radically solve the real problem underlying the diabetic growing epidemic? Let's start talking about Pre-Primary and Primary Prevention of T2DM, based on Diabetic and Dislipidemic-Dependent, Inherited Real Risk, bedside diagnosed from birth with a stethoscope, and removed by inexpensive Reconstructing Mitochodrial Quantum Therapy. The till now open problem in the traditional Accademic Medicine is the clinical diagnosis of T2DM from the First of its Five Stages. Well. Recently, a new and original reliable clinical method for diagnosing DM has been added to a flurry of methods that have existed for twenty years. The Corpus Callosum is the part of the brainthat allows communication between its two hemispheres. It is responsible for transmitting neural messages between both the right and left hemispheres. According to Angiobiopathy Theory, microvessel dynamic parallels the related parenchima cell activity. As a consequence,thanks to Quantum Biophysical Semeiotic, physicians are able to bedside recognize in both qualitative and quantitative way, Corpus Callosum microcirculatory wall dynamics. Notoriously, Diabetic and Dislipidemic Constitution-Dependent, Inherited Real Risk can be recognized with a stethoscope starting from birth (1, 2). Regardless of blood glucose, this predisposition to T2DM is characterized also by an increased synthesis of GH-RH, and especially high activity nucleus of the vagus nerve. therefore by a significant increase in the Corpus Callosum activity, ascertained at the beside, as illustrated in my article (3). Interestingly, at rest, the normal activity of Corpus Callosum, easily and quickly assessed on vary large scale, e.g., during any medical examination, allows to exclude the presence of T2DM, starting from birth, namely from its Inherited Real Risk.
References if allowed by Medscape.
1) Sergio Stagnaro and Simone Caramel.Inherited Real Risk of Type 2 Diabetes Mellitus: bedside diagnosis, pathophysiology and primary prevention. Front Endocrinol (Lausanne). 2013; 4: 17. Published online 2013 Feb 26. doi:[10.3389/fendo.2013.00017]http://www.frontiersin.org/Review/ReviewForum.aspx [ [MEDLINE]
2) Stagnaro S., West PJ., Hu FB., Manson JE., Willett WC. Diet and Risk of Type 2 Diabetes. N Engl J Med. 2002 Jan 24;346(4):297-298. [MEDLINE]
3)Sergio Stagnaro (2018) La Valutazione della Microcircolazione nel Corpo Calloso recita un Ruolo importante nella Diagnostica Clinica Semeiotico-Biofisico- Quantistica. http://www.sisbq.org/uploads/5/6/8/7/5687930/corpocalloso.pdf
4) Simone Caramel, Marco Marchionni and Sergio Stagnaro. The Glycocalyx Bedside Evaluation Plays A Central Role in Diagnosing Type 2 Diabetes Mellitus and in its Primary Prevention. Treatment Strategies - Diagnosing Diabetes, Cambridge Research Centre, Volume 6 Issue 1, Pg 41-43. http://viewer.zmags.com/publication/0aafcae9#/0aafcae9/1
5) Caramel S., Marchionni M., Stagnaro S. Morinda citrifolia Plays a Central Role in the Primary Prevention of Mitochondrial-dependent Degenerative Disorders. Asian Pac J Cancer Prev. 2015;16(4):1675. http://www.ncbi.nlm.nih.gov/pubmed/25743850[MEDLINE]
We would like to thank Anne-Thea McGill and Brown et al for their response to our manuscript “Parental history of type 2 diabetes is associated with lower resting energy expenditure in normoglycemic subjects.” The points raised by the commentaries are well taken. However, as stated in the limitations of our study, we performed a cross-sectional study which did not track weight gain A longitudinal study would be required to gain such specific insights. While predictive models are useful, they are not without limitations and the most accurate determination of weight gain arising from lower resting energy expenditure is best done by a longitudinal study. Lower resting expenditure may not always equate to an energy surplus as energy intake could be lower in subjects with lower REE or physical activity energy expenditure may be higher, thus balancing the total energy expenditure.
It’s appreciated for addressing an interesting area of research about the efficacy of medical nutrition treatment based on the Mediterranean Diet (MedDiet).
The study was a secondary analysis of the St Carlos GDM Prevention Study, conducted between January and December 2015 in Hospital Clinico San Carlos (Madrid, Spain). The author used MedDiet-MNT in order to observe its effects on mother’s glycemic level and also the prenatal outcome.
According to this study, there were two groups. Both groups received dietary recommendation to follow MD guideline, the difference was just in intervention group, they added portion for virgin olive oil and nuts. Basically both groups had similar diet recommendation, so further clinical experiment is highly needed to determine the exact effect of adding portion in extra virgin olive oil and nuts on lowering risk of GDM.
Although this diet had several benefits, the use of adding portion on extra virgin oil and pistachios in the intervention group treatment still becomes a question. In the other study, traditional Mediterranean diet had positive effect on lowering risk of GDM in pregnant women (Izadi, 2016), this outcome also occurred in the study conducted by Perez,Ferre (2014) that MD could reduce risk of GDM. So, if the traditional way has been reported successful in lowering GDM risk, is that really necessary to modify the basic guideline of MedDiet?
It’s appreciated for addressing an interesting area of research about the efficacy of medical nutrition treatment based on the Mediterranean Diet (MedDiet).
The study was a secondary analysis of the St Carlos GDM Prevention Study, conducted between January and December 2015 in Hospital Clinico San Carlos (Madrid, Spain). The author used MedDiet-MNT in order to observe its effects on mother’s glycemic level and also the prenatal outcome.
According to this study, there were two groups. Both groups received dietary recommendation to follow MD guideline, the difference was just in intervention group, they added portion for virgin olive oil and nuts. Basically both groups had similar diet recommendation, so further clinical experiment is highly needed to determine the exact effect of adding portion in extra virgin olive oil and nuts on lowering risk of GDM.
Although this diet had several benefits, the use of adding portion on extra virgin oil and pistachios in the intervention group treatment still becomes a question. In the other study, traditional Mediterranean diet had positive effect on lowering risk of GDM in pregnant women (Izadi, 2016), this outcome also occurred in the study conducted by Perez,Ferre (2014) that MD could reduce risk of GDM. So, if the traditional way has been reported successful in lowering GDM risk, is that really necessary to modify the basic guideline of MedDiet?
References:
1. Izadi V, Tehrani H, Haghighatdoost F, et.al. Adherence to the DASH and Mediterranean diets is associated with decreased risk for gestational diabetes mellitus. Nutrition 2016;32:1092-6. doi:10.1016/j.nut.2016.03.006.
2. Perez-Ferre N, Valle LD, Torrej MJ, et.al. Diabetes Mellitus and Abnormal Glucose Tolerance Development After Gestational Diabetes: A Three-year, Prospective, Randomized, Clinical based, Mediterranean lifestyle Interventional Study with Parallel Groups. Clinical Nutrition 2015;34:579-585. doi:10.1016/j.clnu.2014.09.005.
Humans have proportionately large, complex brains that require large amounts of nutrients- energy and micronutrients. There are a number of little recognised co-adaptations to manage this 'brain drain'. Two very important mechanisms to manage this high localised metabolic rate were to - 1) Use the extremely varied and reactive plant chemicals that were increasingly being consumed in the nomadic hunter-gatherer hominins 2) To increase the buffer stores of nutrients by reactivating mammalian genes for subcutaneous fat stores. 3) increase strong drives to acquire high nutrient food predicated on energy density.
The nutrient chemicals are often plant defence (secondary) chemicals) of which the anti yeast polyphenol resveratrol is but one of myriads, act as Michael acceptors. These reactions are much less precise that enzymatic reactions. They shuffle-reshuffle electrons and efficiently manage energy, reducing free radical production and energy loss . There are a number of enhanced anti-oxidant, detoxification, and adaptive and general cell repair pathways coordinated by the NRF2/Keap1/antioxidant response element cell protection systems.
2) As mentioned, the subcutaneaous adipose tissue is a brain nutrient buffer - especially for the intra-uterine and postnatal human brain development. This adipose is not just a fat store but lipids and many other nutrients should be in the stores - those absorbed through the colon after being trafficked there...
Humans have proportionately large, complex brains that require large amounts of nutrients- energy and micronutrients. There are a number of little recognised co-adaptations to manage this 'brain drain'. Two very important mechanisms to manage this high localised metabolic rate were to - 1) Use the extremely varied and reactive plant chemicals that were increasingly being consumed in the nomadic hunter-gatherer hominins 2) To increase the buffer stores of nutrients by reactivating mammalian genes for subcutaneous fat stores. 3) increase strong drives to acquire high nutrient food predicated on energy density.
The nutrient chemicals are often plant defence (secondary) chemicals) of which the anti yeast polyphenol resveratrol is but one of myriads, act as Michael acceptors. These reactions are much less precise that enzymatic reactions. They shuffle-reshuffle electrons and efficiently manage energy, reducing free radical production and energy loss . There are a number of enhanced anti-oxidant, detoxification, and adaptive and general cell repair pathways coordinated by the NRF2/Keap1/antioxidant response element cell protection systems.
2) As mentioned, the subcutaneaous adipose tissue is a brain nutrient buffer - especially for the intra-uterine and postnatal human brain development. This adipose is not just a fat store but lipids and many other nutrients should be in the stores - those absorbed through the colon after being trafficked there by fibre and released from the (non grain) variably fermentable dietary fibre.
A high nutrient varied diet from heritage and wild type immune competent foods has been supplying healthy humans for the few million years of their evolution... until our
3) particularly strong reward mesolimbic system drives for energy dense foods also fostered new abilities to refine and process dietary items with various technologies. Current agribusiness, mass-monocultural food production and processing have excluded the vast range and volume of complex plant chemicals required. In addition, these refined highly bred or genetically altered/edited foods are often grown and processed with foreign, unnecessary (xenobiotic) or frankly toxic chemicals.
SO, unless the total plant food adequacy, lack of contaminants, genetics (polymorphisms, particularly that of adipose distribution type) and epigenetics is known or modelled, each individual's energetics equations will be different. Many studies show very different results in individuals fed different controlled energy diets - where the micronutrient intake is totally ignored. Often the participants are blamed for not recording their food intake or complying in other ways properly. This is the likely reason for such poor predictions thus far. The inability to explain varied and 'equivocal' results in so many studies has not had an adequate explanation. Modelling human energetics in other animals is not useful due to this set of unusual nutritional and metabolic characteristics.
Human metabolism can only be very generally approximated. This will improve if mathematical systems models using dynamic energy budget equations where both macronutrient and micronutrient reserve factors are corrected for.
We read with great interest the article by Gilbert-Ouimet M et al1 recently published in your journal. Such study showed an interesting result that only increased risk of incidence of diabetes occurring among female workers working 45 hours or more per week, and suggested that modification of such risk factors would be helpful to improve prevention strategies and orient policymaking by following up 7065 workers over a 12-year period in Ontario, Canada.
However, we have some concerns. Firstly, in order to find out the potential relationship between long work hours and the incidence of diabetes, several other independent variables were considered in the analysis process such as sociodemographic and health-related covariates, but the information of menopause and menopausal hormone therapy (MHT) among women was not added. Strong association with increased risk of cardiovascular diseases had been confirmed in several studies and data from large randomized-controlled trials have shown that the decrease of incidence of T2D in women could be achieved by MHT with conjugated estrogens 2,3 . Although the clinical evidence still not be sufficient to recommend the use of hormones for prevention of diabetes among women especially with early menopause or premature ovarian insufficiency4, such detail might be helpful to uncover the neglected association between menopause and increased risk of diabetes.
Secondly, compared with the increased risk...
We read with great interest the article by Gilbert-Ouimet M et al1 recently published in your journal. Such study showed an interesting result that only increased risk of incidence of diabetes occurring among female workers working 45 hours or more per week, and suggested that modification of such risk factors would be helpful to improve prevention strategies and orient policymaking by following up 7065 workers over a 12-year period in Ontario, Canada.
However, we have some concerns. Firstly, in order to find out the potential relationship between long work hours and the incidence of diabetes, several other independent variables were considered in the analysis process such as sociodemographic and health-related covariates, but the information of menopause and menopausal hormone therapy (MHT) among women was not added. Strong association with increased risk of cardiovascular diseases had been confirmed in several studies and data from large randomized-controlled trials have shown that the decrease of incidence of T2D in women could be achieved by MHT with conjugated estrogens 2,3 . Although the clinical evidence still not be sufficient to recommend the use of hormones for prevention of diabetes among women especially with early menopause or premature ovarian insufficiency4, such detail might be helpful to uncover the neglected association between menopause and increased risk of diabetes.
Secondly, compared with the increased risk of incidence of diabetes within women, such risk tended to decrease as the number of work hours increased, which was very interesting. A recent meta-analysis of individual data from 68 prospective studies showed that diabetes increased the risk for occlusive vascular mortality nearly three times among women, so could Gilbert-Ouimet M et al's data be translated into the potential relationship of increased risk of occlusive vascular mortality with more work hours? It would deserve in-depth exploration of the raw data of the Ontario study.
In conclusion, we appreciate Gilbert-Ouimet M et al for their study in sex difference of work hours and incidence of diabetes. It indeed expanded our knowledge of effects of working long hours on diabetes, but further studies are still needed to investigate the potential effects of menopause and MHT on the association between work hour and increased risk of incidence of diabetes and cardiovascular events among women.
REFERENCES:
1. Gilbert-Ouimet M, Ma H, Glazier R, et al. Adverse effect of long work hours on incident diabetes in 7065 Ontario workers followed for 12 years. BMJ Open Diab Res Care 2018; 6: e000496.
2. Kanaya AM, Herrington D, Vittinghoff E, et al. Glycemic effects of postmenopausal hormone therapy: the Heart and Estrogen/progestin Replacement Study. A randomized, double-blind, placebo-controlled trial. Ann Intern Med. 2003; 138: 1-9.
3. Manson JE, Chlebowski RT, Stefanick ML, et al. Menopausal hormone therapy and health outcomes during the intervention and extended poststopping phases of the Women’s Health Initiative randomized trials. JAMA, 2013; 310: 1353-68.
4. Mauvais-Jarvis F, Manson JE, Stevenson JC, et al. Menopausal Hormone Therapy and Type 2 Diabetes Prevention: Evidence, Mechanisms, and Clinical Implications. Endocr Rev. 2017; 38: 173-88.
5. Norhammar A. Diabetes and cardiovascular mortality: the impact of sex. Lancet Diabetes Endocrinol. 2018; 6: 517-519.
ACKNOWLEDGEMENT:
This work was supported by Program of Shanghai Academic Research Leader (17XD1405000), Program for Outstanding Medical Academic Leader (LJRC2015-21), NSFC grants (91539118, 81611130092) to C.L., NSFC grants (81473445,2014ZX09301307-016) to Z.W.
Nyenwe et al. (1) address an interesting and important topic of the effects or associations of parental diabetes with offspring outcomes. However, the paper contains an important error that renders one of their conclusions markedly incorrect.
Specifically, having estimated a difference in energy expenditure among offspring of parents with diabetes (which the authors refer to as ‘parental diabetes’) versus offspring of parents without diabetes, the authors project that persons with parental diabetes will, as a result of this difference, steadily gain substantial weight indefinitely. They state:
“According to the data published by Wishnofsky (2), one pound has a caloric value of 3500 kcal or (1 kg=7700 kcal). We derived the estimated weight gain in kg by dividing the projected energy accrual by 7700. When normalized REE is used for this estimation, subjects with parental diabetes had a daily energy surplus of 125 kcal which would translate to ~6 kg weight gain per year.”
This type of estimation is commonly referred to as the 3500 kcal rule or 3500 kcal per pound rule.
This reasoning and calculation is erroneous because it fails to account for the dynamic changes of energy expenditure that occur with weight gain and loss. Wishnofsky himself noted the complexity of estimating energetic equivalents of gaining or losing body weight, specifically addressing the importance of time, nitrogen balance, tissue type, and water loss, among other factors, on...
Nyenwe et al. (1) address an interesting and important topic of the effects or associations of parental diabetes with offspring outcomes. However, the paper contains an important error that renders one of their conclusions markedly incorrect.
Specifically, having estimated a difference in energy expenditure among offspring of parents with diabetes (which the authors refer to as ‘parental diabetes’) versus offspring of parents without diabetes, the authors project that persons with parental diabetes will, as a result of this difference, steadily gain substantial weight indefinitely. They state:
“According to the data published by Wishnofsky (2), one pound has a caloric value of 3500 kcal or (1 kg=7700 kcal). We derived the estimated weight gain in kg by dividing the projected energy accrual by 7700. When normalized REE is used for this estimation, subjects with parental diabetes had a daily energy surplus of 125 kcal which would translate to ~6 kg weight gain per year.”
This type of estimation is commonly referred to as the 3500 kcal rule or 3500 kcal per pound rule.
This reasoning and calculation is erroneous because it fails to account for the dynamic changes of energy expenditure that occur with weight gain and loss. Wishnofsky himself noted the complexity of estimating energetic equivalents of gaining or losing body weight, specifically addressing the importance of time, nitrogen balance, tissue type, and water loss, among other factors, on estimating the energetic equivalent of one pound of body weight (2, 3). He did not imply that 3500 kcal should be used as the equivalent of one pound of weight in all cases and extrapolated indefinitely.
Over very short periods of time, such a linear projection might be a reasonable rough approximation, but over periods of months or years, the 3500 kcal rule can lead to order-of-magnitude overestimates of weight changes in response to energy intake or expenditure variations (4). This has been noted repeatedly in the literature (5-8), including prominent journals such as New England Journal of Medicine (9), The Journal of the American Medical Association (10, 11), and The Lancet (12). This error has resulted in at least one paper being retracted (13).
Validated mathematical models have been developed to account for the dynamic changes in energy expenditure that occur with weight gain and loss (12). Using such a model, we calculated that the observed 125 kcal/d difference in energy expenditure would produce a total weight change of ~6.5 kg, with ~3.9 kg gained in the first year and 95% of the total gained in 3 years. These model calculations incorporated the baseline demographics and anthropometrics reported by Nyenwe et al. and assumed that the subjects had a constant energy intake and a physical activity level of 1.7. Even the simple 10 kcal/d per pound rule of thumb (or equivalently 100 kJ/d per kg) derived from a more detailed mathematical model (12) predicts a total weight change of ~6 kg, with half of the gain occurring in the first year and 95% of the total gain in 3 years. These estimates stand in marked contrast to the predicted ~6 kg of weight gain every year stated by Nyenwe et al.
We encourage the authors to revise their conclusion regarding projected weight effects of the estimated differences in energy expenditure.
References:
1. Nyenwe EA, Ogwo CC, Owei I, et al. Parental history of type 2 diabetes is associated with lower resting energy expenditure in normoglycemic subjects. BMJ Open Diabetes Research & Care 2018;6(1) doi: https://www.doi.org/10.1136/bmjdrc-2018-000511
4. Brown AW, Hall KD, Thomas D, et al. Order of Magnitude Misestimation of Weight Effects of Children's Meal Policy Proposals. Childhood Obesity 2014;10(6):542-5. doi: https://www.doi.org/10.1089/chi.2014.0081
5. Hall KD, Chow CC. Why is the 3500 kcal per pound weight loss rule wrong? International Journal of Obesity 2013;37(12):10.1038/ijo.2013.112. doi: https://www.doi.org/10.1038/ijo.2013.112
6. Thomas DM, Martin CK, Lettieri S, et al. Response to 'why is the 3500 kcal per pound weight loss rule wrong?'. Int J Obes 2013;37(12):1614-5. doi: https://www.doi.org/10.1038/ijo.2013.113
7. Thomas DM, Martin CK, Lettieri S, et al. Can a weight loss of one pound a week be achieved with a 3500-kcal deficit? Commentary on a commonly accepted rule. Int J Obes 2013;37(12):1611-3. doi: https://www.doi.org/10.1038/ijo.2013.51
8. Bohan Brown MM, Brown AW, Allison DB. Linear extrapolation results in erroneous overestimation of plausible stressor-related yearly weight changes. Biological Psychiatry 2014 doi: https://www.doi.org/10.1016/j.biopsych.2014.10.028
9. Casazza K, Fontaine KR, Astrup A, et al. Myths, presumptions, and facts about obesity. N Engl J Med 2013;368(5):446-54. doi: https://www.doi.org/10.1056/NEJMsa1208051
12. Hall KD, Sacks G, Chandramohan D, et al. Quantification of the effect of energy imbalance on bodyweight. Lancet 2011;378(9793):826-37. doi: https://www.doi.org/10.1016/S0140-6736(11)60812-X
13. Retraction of “Modeling Potential Effects of Reduced Calories in Kids' Meals with Toy Giveaways”. Childhood Obesity 2014;10(6):546-46. doi: https://www.doi.org/10.1089/chi.2014.1062
The Authors provide a thorough examination of a wide series of items related to AI in DR screening, including medico-legal issues, still under way of definition worldwide. Most articles strengthen reliability data, mainly useful to diabetologists facing DR screening, being provided with a suggestion (usually green or red flags) by the AI system. In my opinion, the workflow following a red flag has to be well-specified yet: some systems correctly suggest that red flagged patients follow a preferred pathway for a human examination, but the term "preferred" may vary owing to local organisational issues, mainly in LMICs. In my opinion and experience, one must keep in mind that red flags don't inform about how impending a vision loss can be: sometimes, bleeding of a correctly recognized proliferation, or reaching the fovea by correctly identified fluid and exudates approaching it, is a matter of hours. In such cases, missing the need for speed can worsen patients' sight and raise not-yet-defined medico-legal issues. So, I believe it would be safe to obtain an immediate ophthalmologist's or trained diabetologist's examination of all red-flagged images, what is nowadays made really easy by telemedicine.
Dear Editor
Show MoreThis indeed a very good article on emerging class of antidiabetic drugs i.e SGLT2 inhibitors. SGLT2 inhibitors are making their way not only for their role as an adjuvant therapy for control of diabetes, but their beneficial role in providing cardiac safety, renal protection and weight reduction are making these drugs superior in comparison to DPP4 inhibitors, which are another widely used and well tolerated anti diabetic drugs. SGLT2 inhibitors are known to lower blood glucose by inhibiting glucose and sodium re absorption and promoting glycosuria, as a consequence they cause glucose and HbA1C reduction and lowering of blood pressure1. A part from these benefits , SGLT2 inhibitors might acquire potential indication to be used for prevention and treatment of gout due to their uric acid reducing properties2.
Since these drugs got FDA approval and become available, the side effect profile of these drugs have always remained talk of major debates. Well known side effects are genital infection, increase incidence of mycotic infections and diabetic ketoacidosis. One of the major and serious concern with use of SGLT2 inhibitors is possibility of Fournier’s gangrene. Fournier’s gangrene is an extremely rare but life-threatening bacterial infection of the genital tissue. Current article is also reflection of my own experience. I have been prescribing SGLT2 inhibitors quite frequently and most of the patients are in regular follow up and I have not seen any...
We thank the authors for their question and interest in our article. The two cited articles (1,2) are very interesting but differ from what we wanted to show with the St. Carlos GDM Prevention Study (3). The first one is a case-control study analyzing associations of DASH and Mediterranean diets with GDM (1). The second one evaluates the effect of a nutritional intervention with a Mediterranean diet on postpartum development of glucose disorders in women with prior GDM (2). The St. Carlos GDM Prevention Study was a randomized controlled trial that analyzed the effect a nutritional intervention with a MedDiet, supplemented with extra virgin olive oil and nuts, on GDM development.
Show MoreThe motive women were given extra virgin olive oil was to ensure a high compliance with the MedDiet. Not only women increased their intake in these two foods, but also increased their overall MEDAS score (3). This also seemed to translate in a substitution of unhealthy foods for healthy ones. For example, a substitution of unhealthy snacks for nuts and of processed sauces and dressings for olive oil and olive oil-based sauces. The ultimate message we were hoping to convey is that extra virgin olive oil and nuts should be consumed more, with less restrictions. Current Spanish guidelines advise a controlled consumption of these foods in pregnancy.
The type of medical nutrition therapy used in GDM treatment is not standardized and can be different between centers. Due to the results found...
As author of the Diabetes Health Profile, I felt that overall the paper provided a generally balanced report of your study, I have however, a number of issues regarding your report.
First, although resulting in a high alpha coefficient (0.79), it is incorrect to calculate an alpha score for the total number of items when the scale itself is multidimensional (Oranges and apples). In doing so, it can result in an overall low alpha score. In this case it is fortunate that the value was high. Had this been a low score this would have been perceived as a negative result to the less knowledgeable.
Secondly, with regard to responsiveness to change, a crude method for measuring change in score was used together with a very limited patient sample. Although the limitation of the methodology was discussed to some extent in the discussion, it would have been preferable at least to measure at both pre and post for each of the three scale domains. Minimally Important Difference (MID) values are available for the DHP that would enable the smallest change in score that is clinically significant to be measured.
Thirdly, in the section ‘Significance of the study’ it would have been more appropriate that the final comment on implementation in clinical practice and studies should have been limited to the ‘Norwegian’ version of the DHP-18. As currently phrased this is rather general and suggests the use of the DHP-18 in clinical studies per se.
Finally, permi...
Show MoreT2DM first problem still open is to recognize diabetics so far without proper diagnosis, in order to avoid the series of complications that arise decades before the clinical diabetic symptomatology decades before the clinical diabetic symptomatologyFDA Commissioner Scott Gottlieb, MD, said: "Diabetes affects nearly 30 million Americans. Access to affordable insulin is literally a matter of life and death". Aurobindo would say this is a true and false statement. Why do we all, including FDA, not radically solve the real problem underlying the diabetic growing epidemic? Let's start talking about Pre-Primary and Primary Prevention of T2DM, based on Diabetic and Dislipidemic-Dependent, Inherited Real Risk, bedside diagnosed from birth with a stethoscope, and removed by inexpensive Reconstructing Mitochodrial Quantum Therapy. The till now open problem in the traditional Accademic Medicine is the clinical diagnosis of T2DM from the First of its Five Stages. Well. Recently, a new and original reliable clinical method for diagnosing DM has been added to a flurry of methods that have existed for twenty years. The Corpus Callosum is the part of the brainthat allows communication between its two hemispheres. It is responsible for transmitting neural messages between both the right and left hemispheres. According to Angiobiopathy Theory, microvessel dynamic parallels the related parenchima cell activity. As a consequence,thanks to Quantum Biophysical Semeiotic, physi...
Show MoreWe would like to thank Anne-Thea McGill and Brown et al for their response to our manuscript “Parental history of type 2 diabetes is associated with lower resting energy expenditure in normoglycemic subjects.” The points raised by the commentaries are well taken. However, as stated in the limitations of our study, we performed a cross-sectional study which did not track weight gain A longitudinal study would be required to gain such specific insights. While predictive models are useful, they are not without limitations and the most accurate determination of weight gain arising from lower resting energy expenditure is best done by a longitudinal study. Lower resting expenditure may not always equate to an energy surplus as energy intake could be lower in subjects with lower REE or physical activity energy expenditure may be higher, thus balancing the total energy expenditure.
It’s appreciated for addressing an interesting area of research about the efficacy of medical nutrition treatment based on the Mediterranean Diet (MedDiet).
The study was a secondary analysis of the St Carlos GDM Prevention Study, conducted between January and December 2015 in Hospital Clinico San Carlos (Madrid, Spain). The author used MedDiet-MNT in order to observe its effects on mother’s glycemic level and also the prenatal outcome.
According to this study, there were two groups. Both groups received dietary recommendation to follow MD guideline, the difference was just in intervention group, they added portion for virgin olive oil and nuts. Basically both groups had similar diet recommendation, so further clinical experiment is highly needed to determine the exact effect of adding portion in extra virgin olive oil and nuts on lowering risk of GDM.
Although this diet had several benefits, the use of adding portion on extra virgin oil and pistachios in the intervention group treatment still becomes a question. In the other study, traditional Mediterranean diet had positive effect on lowering risk of GDM in pregnant women (Izadi, 2016), this outcome also occurred in the study conducted by Perez,Ferre (2014) that MD could reduce risk of GDM. So, if the traditional way has been reported successful in lowering GDM risk, is that really necessary to modify the basic guideline of MedDiet?
References:
Show More1. Izadi V, Tehrani H, Haghighatdoost F, et.a...
Humans have proportionately large, complex brains that require large amounts of nutrients- energy and micronutrients. There are a number of little recognised co-adaptations to manage this 'brain drain'. Two very important mechanisms to manage this high localised metabolic rate were to - 1) Use the extremely varied and reactive plant chemicals that were increasingly being consumed in the nomadic hunter-gatherer hominins 2) To increase the buffer stores of nutrients by reactivating mammalian genes for subcutaneous fat stores. 3) increase strong drives to acquire high nutrient food predicated on energy density.
Show MoreThe nutrient chemicals are often plant defence (secondary) chemicals) of which the anti yeast polyphenol resveratrol is but one of myriads, act as Michael acceptors. These reactions are much less precise that enzymatic reactions. They shuffle-reshuffle electrons and efficiently manage energy, reducing free radical production and energy loss . There are a number of enhanced anti-oxidant, detoxification, and adaptive and general cell repair pathways coordinated by the NRF2/Keap1/antioxidant response element cell protection systems.
2) As mentioned, the subcutaneaous adipose tissue is a brain nutrient buffer - especially for the intra-uterine and postnatal human brain development. This adipose is not just a fat store but lipids and many other nutrients should be in the stores - those absorbed through the colon after being trafficked there...
To the Editor
We read with great interest the article by Gilbert-Ouimet M et al1 recently published in your journal. Such study showed an interesting result that only increased risk of incidence of diabetes occurring among female workers working 45 hours or more per week, and suggested that modification of such risk factors would be helpful to improve prevention strategies and orient policymaking by following up 7065 workers over a 12-year period in Ontario, Canada.
Show MoreHowever, we have some concerns. Firstly, in order to find out the potential relationship between long work hours and the incidence of diabetes, several other independent variables were considered in the analysis process such as sociodemographic and health-related covariates, but the information of menopause and menopausal hormone therapy (MHT) among women was not added. Strong association with increased risk of cardiovascular diseases had been confirmed in several studies and data from large randomized-controlled trials have shown that the decrease of incidence of T2D in women could be achieved by MHT with conjugated estrogens 2,3 . Although the clinical evidence still not be sufficient to recommend the use of hormones for prevention of diabetes among women especially with early menopause or premature ovarian insufficiency4, such detail might be helpful to uncover the neglected association between menopause and increased risk of diabetes.
Secondly, compared with the increased risk...
Nyenwe et al. (1) address an interesting and important topic of the effects or associations of parental diabetes with offspring outcomes. However, the paper contains an important error that renders one of their conclusions markedly incorrect.
Specifically, having estimated a difference in energy expenditure among offspring of parents with diabetes (which the authors refer to as ‘parental diabetes’) versus offspring of parents without diabetes, the authors project that persons with parental diabetes will, as a result of this difference, steadily gain substantial weight indefinitely. They state:
“According to the data published by Wishnofsky (2), one pound has a caloric value of 3500 kcal or (1 kg=7700 kcal). We derived the estimated weight gain in kg by dividing the projected energy accrual by 7700. When normalized REE is used for this estimation, subjects with parental diabetes had a daily energy surplus of 125 kcal which would translate to ~6 kg weight gain per year.”
This type of estimation is commonly referred to as the 3500 kcal rule or 3500 kcal per pound rule.
This reasoning and calculation is erroneous because it fails to account for the dynamic changes of energy expenditure that occur with weight gain and loss. Wishnofsky himself noted the complexity of estimating energetic equivalents of gaining or losing body weight, specifically addressing the importance of time, nitrogen balance, tissue type, and water loss, among other factors, on...
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