HRT reduces the onset of diabetes in menopausal women

Nov 24, 2021Oct 13, 2021 kaitiscotland1 Comment

Type 2 Diabetes Delayed by Menopause Hormone Therapy

Mar 16, 2021 Editor: David L. Joffe, BSPharm, CDE, FACA
Author: Mit Suthar, PharmD. Candidate, LECOM School of Pharmacy

The mechanisms by which estrogens / hormone therapy improve glucose homeostasis and delay diabetes are not completely understood.

Franck Mauvais-Jarvis, MD., director of the Tulane Diabetes Research Program at Tulane University Health Sciences Center, New Orleans, explained at the Annual World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease: “During the menopause transition, women accumulate metabolic disturbances, including visceral obesity, systemic inflammation, insulin resistance, dyslipidemia, and hypertension. They also lose muscle mass. Some of these abnormalities are partially explained by chronological aging, but they are also caused by estrogen deficiency. There’s a synergism between aging and estrogen deficiency.”

Almost 30 years ago, researchers investigated the connection between postmenopausal hormone use and the subsequent incidence of non-insulin dependent diabetes in a prospective cohort of 21,028 postmenopausal US women aged 30-55 years. These women were registered in the Nurse’s Health Study and monitored for 12 years (Ann Epidemiol. 1992;2[5]:665-73).

Interestingly, during this study they found that the patients who were on hormone therapy experienced a 20% reduction in the incidence of type 2 diabetes. A newer study from 2009 analyzed the association between the use of hormone therapy and new-onset diabetes in 63,624 postmenopausal women. These patients were enrolled in the prospective French cohort of the Etude Epidemiologique de Femmes de la Mutuelle Générale de l’Education Nationale (E3N) and followed for 15 years (Diabetologia. 2009;52[10]:2092-100). This study also found that participants who were taking hormone therapy also experienced a 20% reduction in the incidence of type 2 diabetes.

In another study called the Heart and Estrogen/Progestin Replacement Study researchers evaluated the effect of hormone therapy on fasting glucose level and incident diabetes. 20 US centers reported on 2,763 postmenopausal women with coronary heart disease (Ann Intern Med. 2003;138[1]:1-9). The study participants received 0.625mg of conjugated estrogen with 2.5mg of medroxyprogesterone, or placebo, and were followed for 4 years. The research discovered that patients who were treated with hormone therapy had a 35% reduction in the incidence of diabetes.

Dr. Mauvais-Jarvis stated that the strongest data came from the Women’s Health Initiative (WHI), which was a randomized, double-blind trial (Diabetologia. 2004; 47[7]:1175-87). This trial compared the effect of daily 0.625mg conjugated estrogen and 2.5mg medroxyprogesterone acetate with placebo during 5.6 years of monitoring.
This trial also revealed a 20% decrease in the incidence of diabetes after 5 years. The researchers found that the protection from diabetes was present whether the WHI participants took just estrogen alone or estrogen plus medroxyprogesterone (N Engl J Med. 2016;374:803-6).

Results from research published in 2006 from a meta-analysis of 107 trials (Diabetes Obes Metab. 2006;8[5]:538-54) found that in women without diabetes, hormone therapy decreased the HOMA-IR (Homeostatic Model Assessment for Insulin Resistance) score by 13% and incidence of type 2 diabetes by 30%. Women with diabetes who took hormone therapy had their fasting glucose reduced by 11% and HOMA-IR by 36%.

Dr. Mauvais-Jarvis explains that the mechanisms by which estrogens improve glucose homeostasis are not completely understood. “One of the most important [mechanisms] is a decrease in abdominal fat, which improves insulin resistance and systemic inflammation. However, in the WHI, it was clear that the improvement in HOMA-IR was independent from the body weight and fat. Estrogen has also been found to increase insulin clearance and sensitivity, increase glucose disposal and effectiveness and decrease sarcopenia. There are fewer than 20 studies looking at beta-cell function. Half of them have shown that estrogen improves insulin secretion.” The idea that the benefits of hormone therapy are independent of weight loss for reducing the incidence of diabetes is certainly encouraging.

Significant factors about the benefits and disadvantages of hormone therapy include the route of administration, and adverse effects of the therapies. Oral estrogens can increase liver exposure to estrogen, increase triglycerides, and increase clotting factors, but an advantage is that oral estrogen is a cheaper form than the transdermal form. Transdermal delivery of estrogen does not raise triglycerides, clotting factors, or inflammatory factors, and presents less exposure to the liver.

Dr. Mauvis-Jarvis and colleagues also evaluated the effect of conjugated estrogens plus bazedoxifene in mice (Mol Metab. 2014;3[2]:177-90). The reason bazedoxifene was combined to estrogen was to preserve the beneficial effects of estrogen but block the estrogen in the breast and uterus, thus decreasing the risk of cancer.

The unforeseen benefits of menopausal hormone therapy cannot be ignored in regard to the decreased incidence of diabetes in patients who take these hormonal therapies. While it is doubtful that hormone therapy will ever be approved for a diabetic indication due to the various complexities of said therapy, hormonal therapy should not be denied to patients with an approved indication who are at increased risk for developing diabetes.

Practice Pearls:

Menopausal hormone therapy can significantly reduce the incidence of diabetes in patients who have an indication for hormone therapy and are at risk for developing diabetes.
Both older and more recent trials have demonstrated this reduction in incidence, which is around 20%
The mechanisms by which estrogens improve glucose homeostasis are not completely understood and the risks of estrogen therapy, such as cancer risk, must be accounted for on a patient by patient basis

Brunk, Doug. “Menopause Hormone Therapy Found to Delay Type 2 Diabetes.” MDedge Endocrinology, MDedge, 31 Jan. 2020.

Mit Suthar, PharmD. Candidate, LECOM School of Pharmacy

Improved life expectancy for severe kidney disease on keto diets

Nov 18, 2021Oct 13, 2021 kaitiscotland1 Comment

Teresa Rodriguez is a Florida USA specialist dietician who has undertaken training with the Charlie Foundation to provide help to patients who have severe kidney disease of various types. Some conditions, previously thought to be untreatable, such as Polycystic Kidney Disease respond to the ketogenic diet and the quality of life and life expectancy for these people has been transformed.

Teresa sees patients in person and coaches them online and via Facebook. She is expecting her book, aimed at both physicians and patients, Keto for Kidney Disease, to be published in March 22.

Teresa comes from Puerto Rico and speaks fluent Spanish and American English and can provide learning in both languages.

I was one of several doctors who were treated to an online presentation by Teresa recently, and was amazed to see how different her approach and results are compared to NHS “usual” treatment and results.

I was taught that there wasn’t really much you could do about Polycystic Kidneys except for dialysis and transplantation when the kidneys eventually failed. She explained that PKD is actually a metabolic condition and that it responds to a ketogenic diet of usually 20g carbohydrate a day. There can be other aggravating factors such as oxalate overload and the kidney needs support to avoid the formation of kidney stones. Many patients will need to drink lemon juice in the mornings and have a much higher fluid intake than usual.

She optimises the patient’s diet based on the results of a detailed clinical history and blood and urine results. She finds that Cystatin C is a much more reliable predicator of kidney function than standard tests such as Creatinine Clearance. She often has to modify drug prescriptions. The blood pressure must be kept within normal limits to reduce deterioration in kidney function but Calcium channel blockers are not beneficial in PKD compared to ACE inhibitors and Sartans. Metformin, however is beneficial.

There is increasing interest in Ketogenic Diet Therapy and Therapeutic Carbohydrate Restriction worldwide.

Metformin improves surgery results in type 2 patients

Nov 12, 2021Aug 23, 2021 kaitiscotland1 Comment

Improved Post-Surgical Outcomes in Patients Using Metformin

Feb 13, 2021 Editor: Steve Freed, R.PH., CDE
Author: Abdullah Al-Ajmi, PharmD Candidate, Skaggs School of Pharmacy and Pharmaceutical Sciences

Metformin use was associated with lower inflammatory markers before surgery, leading to improved outcomes post-surgery.

Around a third of patients >65 years in the U.S. have type 2 diabetes (T2DM). Due to diabetes complications, renal and cardiac comorbidities are common in many patients, leading to impaired inflammatory responses and reduced time to recovery. Also, around half of this patient population undergoes surgical treatment during their lifetime. Therefore, these effects may lead to increased morbidity and mortality post-surgery.

Patients with T2DM have commonly been prescribed metformin as first-line therapy. In addition to its impact on blood glucose control, it has been shown to reduce chronic inflammation. These effects have been studied in diseases linked with the aging process, such as cardiovascular and renal diseases. Previous literature regarding the use of metformin has shown that it reduces all-cause mortality and cardiovascular and renal complications. However, whether metformin use pre-surgery can improve patients’ outcomes post-surgery was not studied before.

A new study aimed to assess the effect of metformin on post-surgical outcomes in patients with T2DM. The study design was retrospective, including patients with T2DM who underwent surgery and were eligible for metformin use. It excluded patients with type 1 diabetes or impaired renal function, since metformin is not indicated in those cases. The investigators compared the patients’ outcomes based on whether they received metformin before surgery or not. Since metformin’s effect on inflammation is based on its use over time, patients’ glycemic control was not considered in the enrollment process. They included patients with an increased risk of mortality or readmission.

The study data was collected from January 2010 to January 2016, and the follow-up continued to December 2018.

Metformin exposure was considered if the patient received at least one prescription within six months before surgery and prescribed the last doctor’s prescription before surgery. Patients who did not meet these criteria were considered not exposed to metformin and fell in the comparison group. Those who are not indicated to use metformin were excluded from the study. The study identified the primary outcome to be 90 days mortality post-surgery. Additionally, secondary outcomes were identified, including 30-day mortality, readmission within three months post-surgery, 5-year survival rate, and the level of the inflammatory marker neutrophil to leukocyte ratio (NLR) pre-surgery.

The study included 5,460 patients who were matched at a 1:1 ratio between the study groups. Patient characteristics were similar between the groups. In the metformin group, around 2% of deaths were reported within a month of surgery. Also, 3% of deaths were reported after three months and 13% in the 5th year. On the other hand, the non-metformin group showed a similar 2% death rate in the first month, but the rates increased to 5% and 17% by three months and five years, respectively. The risk reduction associated with metformin use is considered statistically significant (1.28%; 95% CI, 0.26–2.31). The results also indicate that metformin use was associated with a statically significant reduction in 90-day and 5-year mortality. These outcomes were similar to most surgical interventions except in neurosurgery, which did not show a significant risk reduction with the use of metformin. When comparing hospital readmissions, metformin use was associated with significantly lower readmission rates from 1 to 3 months after discharge than patients who did not receive metformin. Moreover, patients in the metformin group had lower NLR levels before surgery.

The study findings suggest that metformin has additional mechanisms of action to its known means for glycemic control. The reduction of the NLR before surgery is associated with a decrease in morbidity and mortality post-surgery. The study has several limitations, one of which the possibility of confounding variables due to its design. One reason is that the type of surgery was evenly distributed between cohorts. Different surgeries can cause additional surgical stress to the patients, which may affect the study’s outcome. Also, the retrospective nature may introduce selection bias during the data collection phase. Furthermore, the author indicated that the mortality and admission rate might have been misrepresented.

Practice Pearls:

Metformin use in patients with T2DM is associated with a reduced mortality risk post-surgery.
Readmission post-discharge is reduced with metformin use before surgery in patients with T2DM.
Patients with T2DM on metformin have lower inflammatory markers before surgery, leading to improved outcomes post-surgery.

Reitz, Katherine M. et al. “Association Between Preoperative Metformin Exposure And Postoperative Outcomes In Adults With Type 2 Diabetes”. JAMA Surgery, vol 155, no. 6, 2020, p. e200416. American Medical Association (AMA), doi:10.1001/jamasurg.2020.0416.

Campbell, Jared M. et al. “Metformin Reduces All-Cause Mortality And Diseases Of Ageing Independent Of Its Effect On Diabetes Control: A Systematic Review And Meta-Analysis.” Ageing Research Reviews, vol 40, 2017, pp. 31-44. Elsevier BV, doi:10.1016/j.arr.2017.08.003.

Abdullah Al-Ajmi, PharmD Candidate, Skaggs School of Pharmacy and Pharmaceutical Sciences

Kriss Kresser: What to eat instead of the fat hidden in processed foods

Nov 6, 2021Aug 23, 2021 kaitiscotland1 Comment

*If you think these are the healthy option, you must read this post*

Industrial seed oils are sold in big plastic containers of bright gold liquid, and although some of us will buy these to deep and shallow fry foods at home, most of the seed oils we eat will be hidden in processed foods, often marketed as convenient and healthy.

When ingested, these oils cause a low grade inflammatory process that can aggravate and sometimes cause such diverse conditions as: diabetes, obesity, cardiovascular disease, macular degeneration of the eyes, osteoarthritis, gut pain, asthma, autoimmune illnesses, dementia and mental health problems.

Kriss Kresser explains why these oils should be avoided and what fats to eat instead. Of course, this largely means ditching processed foods, if you haven’t already.

https://chriskresser.com/how-industrial-seed-oils-are-making-us-sick/

ADA cut target HbAIC for children to 7%

Oct 31, 2021Aug 23, 2021 kaitiscotland1 Comment

More Stringent HbA1C Targets for Children and Adolescents with Type 1 Diabetes

Mar 2, 2021 Editor: David L. Joffe, BSPharm, CDE, FACA
Author: Adrian Gavre, PharmD Candidate, Philadelphia College of Osteopathic Medicine

What do the new ADA guidelines for HbA1C have to say about treating children and adolescents with type 1 diabetes?

Recently, the American Diabetes Association (ADA) recommended lowering the target hemoglobin A1C (HbA1C) guidelines for children with type 1 diabetes (T1D).

A study conducted by Redondo et al. has shown that stricter controls of HbA1C within this population resulted in improved patient outcomes. Specifically, it was revealed that chronically elevated blood glucose levels in children could lead to increased rates of several serious effects, such as abnormal brain development; cardiac issues including stroke, coronary, peripheral heart disease; and other diabetic complications, nephropathy, neuropathy, and retinopathy. Better control of blood glucose levels lowered these events’ incidence and improved mortality rates in children and adolescents with T1D. http://imasdk.googleapis.com/js/core/bridge3.476.0_en.html#goog_25686799Volume 0%

Regarding abnormal brain development, one meta-analysis (n=1619) showed that patients with T1D had lower inhibition, working memory, and executive function compared to control subjects. In a study regarding microvascular diseases, patients with lower HbA1C had a significantly lower risk of microvascular diseases than patients with higher HbA1C (mean Hba1C 8.06% vs. 9.76%). A study conducted by the Swedish National Diabetes Register found a risk over fourfold for all-cause mortality, over sevenfold for cardiovascular mortality, and elevenfold for cardiovascular disease in patients diagnosed with T1D under age ten compared to the control group.

Due to this study’s results, the ADA 2020 Standards of Medical Care recommends that children and adolescents with T1D target an HbA1C goal of less than 7%. This is a change from their 2019 guidelines, which had a target HbA1C goal of less than 7.5%.

The study suggests that more intensive insulin therapy is the preferred strategy to treat children and adolescents with T1D. Instead of simply treating a patient’s hyperglycemia with insulin, it would be more beneficial to more aggressively bring blood glucose levels to a normal range. More aggressive blood glucose treatment seems to be the best strategy that results in a lower incidence of diabetes-related complications and long-term organ damage.

However, caution should be used in this approach as more aggressive insulin therapy and lower HbA1C targets often result in a higher incidence of hypoglycemia. Symptoms of hypoglycemia are severe and can include dizziness, seizures, coma, and death. Despite this, the study has found that the incidence of hypoglycemia in children and adolescents with T1D has been steadily declining over the past three decades. The Danish Adult Diabetes Database (DADD) found an annual decrease of 8.4% in hypoglycemia incidence in children under 15 with type 1 diabetes from 1995-2016. Another similar study showed no significant difference in hypoglycemia rates in children who had an A1C <7% compared to children who had an A1C between 8-9% (n=1,770). Over this time, the lowered hypoglycemia rates coincide with innovations in drug therapies and technologies, such as insulin analogs, insulin pumps, and continuous glucose monitoring.

These innovative technologies make it easier than ever to keep a patient’s HbA1C within a prespecified range and reduce the risk of hypoglycemia. The ADA still recommends a target of 7.5% for patients too young to properly articulate hypoglycemic symptoms, or patients who do not have access to these innovative technologies. An HbA1C score of less than 8% is acceptable for patients with a severe history of hypoglycemia or a shortened life expectancy due to other pre-existing conditions.

Practice Pearls:

The ADA recently recommended lowering the target HbA1C from 7.5% to 7% for children with type 1 diabetes.
Lowering the target HbA1C in children and adolescents with type 1 diabetes reduces the risks of developing diabetic complications such as nephropathy, neuropathy, and retinopathy, abnormal brain development, and cardiac disorders, and improves mortality.
Although more aggressive insulin regimens can result in hypoglycemia, hypoglycemia rates in children and adolescents with type 1 diabetes have decreased over the past three decades due to innovative new technologies and therapies such as insulin analogs, insulin pumps, and continuous glucose monitoring.

Redondo, M, et al. “The Evolution of Hemoglobin A1c Targets for Youth With Type 1 Diabetes: Rationale and Supporting Evidence.“

Adrian Gavre, PharmD Candidate, Philadelphia College of Osteopathic Medicine  

Dr Gil Wilshire: Resource for women with polycystic ovary syndrome

Oct 25, 2021Aug 23, 2021 kaitiscotlandLeave a comment

*Dr Gil Wilshire has treated thousands of women with polycystic ovary syndrome over 30 years*

Dr Wilshire is a USA gynaecologist who recommends low carbing, also known as a reduced carbohydrate therapeutic diet, for his patients who wish to improve their weight, symptoms and fertility.

His You Tube Videos are collected here for your interest. Please feel free to recommend them to women you know who are afflicted. This is thought to be about one in ten women.

Don’t over treat blood pressure in the over 75s

Oct 19, 2021Aug 21, 2021 kaitiscotland2 Comments

The lowest mortality in people over the age of 75 occurred in those with a systolic blood pressure of 140-160 and a diastolic pressure of 80-90.

These figures are different than for the middle aged, young retirees and those with diabetes, who are often told to shoot for systolic BPs of 130 to 140.

It was reported Age and Ageing that an analysis of a primary care database that strict blood pressure control can actually be detrimental. Frail older adults do particularly poorly when their blood pressures are too low.

My comment: I remember doing four house calls in a row one warm summer’s day to see older adults, all at different addresses, who had collapsed from over treated blood pressure. None came to serious harm but they could have had fractures, sustained head injuries or collapsed in the street. I have read that a higher blood pressure in older life helps to perfuse the kidneys better. For many patients, they see nurses at nurse led clinics and lower blood pressures are not remarked on. They are told “good, come back in six months or a year”. They only see GPs when the blood pressure is considered to be too high. Instead, patients may be better to have realistic targets set by their GP depending on their age and ongoing health issues and check their blood pressure at home where it is less likely to be artificially raised by anxiety that is common in the health care setting.

Saving lives from cardiac arrest in young athletes

Oct 13, 2021Aug 21, 2021 kaitiscotland1 Comment

Adapted from BMJ Oct 10 2020

Ventricular fibrillation with cardiac arrest is the most common cause of death in young athletes.

Unless there has just been physical contact with another player it is best to assume that someone who collapses on a playing field should be considered to have had a cardiac arrest until proven otherwise.

Breathing can continue for half a minute after cardiac arrest and jerking of the limbs is common.

In this situation, begin chest compressions immediately and send for an automated defibrillator and ambulance crew.

My comments: Chest compressions are done to the Bee Gees “Staying Alive”. Don’t waste your time with rescue breaths as these don’t improve survival. Defibrillation is the key and survival reduces by 10% per minute post collapse.

From British Journal of Sports Medicine.

Omega 3 fatty acids are an easy way improve life expectancy

Oct 7, 2021Aug 21, 2021 kaitiscotland1 Comment

A study reported in the American Journal of Clinical Nutrition has found that the highest levels of omega 3 fatty acids found in red blood cells were strongly associated with corresponding increased life expectancy.

This was a longitudinal study over 11 years. People in the top 5th of the erythrocyte fatty acid group had a life expectancy of 5 years more than the people in the bottom 5th.

This is actually as strong an association with mortality and cardiovascular events as traditional factors such as blood pressure, serum lipids and diabetes.

It is never too late to stop smoking

Oct 1, 2021Aug 21, 2021 kaitiscotland1 Comment

There are far fewer smokers now and many have transferred from cigarettes to the more benign vaping devices. Everyone knows not to start or stop if they possibly can, particularly people with diabetes, cardiovascular and lung disease. But is there a point when stopping becomes pointless?

Researchers performed a prospective cohort study with 517 Russian smokers who had been diagnosed with early stage, non small cell lung cancer.

Life lasted a whopping 21.6 months longer in those who stopped smoking soon after diagnosis.