Metformin improves blood sugar and vascular health in type one children

 From Diabetes in Control: Metformin Improves Vascular Health in Children With Type 1 Diabetes
Nov 18, 2017
In individuals with type 1 diabetes (T1DM), cardiovascular disease (CVD) is a major issue and the primary cause of death.

Vascular changes can be detected years before progression to CVD. Targeting blood sugar regulation early in patients at high risk of developing T1DM and in those already diagnosed with T1DM, could potentially help reduce vascular dysfunction risk and even reverse changes already made in vascular function.

Past studies have shown that in adults with T1DM, metformin reduces HbA1c, BMI, and required insulin doses. It has also been suggested that metformin leads to reduced cardiovascular events and better blood sugar regulation in patients with type 2 diabetes. Studies conducted on children with T1DM suggest the same benefits. However, there is currently no research on how metformin affects vascular function in children with T1DM.
A double blind, randomized, placebo-controlled trial was conducted to evaluate the association between metformin and vascular health in children with T1DM over a 12-month period. The study included a total of 90 children from a Women’s and Children’s Hospital in South Australia.  Children were randomly divided into two groups to receive either the metformin intervention or the placebo intervention. Children who weighed 60kg or greater received 1gm of metformin twice daily and those who weighed less than 60kg received 500mg twice daily. Doses were then increased to the complete dose over a period of 2 to 6 weeks.
Follow-up was conducted at 3, 6, and 12 months from the start of the study. Vascular function was obtained at baseline and at every follow-up visit using the brachial artery ultrasound, HbA1C, insulin dose, and BMI were among some of the other outcomes measured.
Results show that vascular function defined by GTN improved over the 12-month period by 3.3% in the metformin intervention group regardless of HbA1c when compared to the placebo group (95% CI 0.3 to 6.3; P=0.03). GTN was found to be the highest in the metformin group at 3 months when compared to placebo. Children in the metformin group also experienced significant improvement (P=0.001) in HbA1c levels at 3 months (8.4%; 95% CI 8.0 to 8.8) (68mmol/mol; 95% CI 64 to 73) when compared to the placebo group (9.3%; 95% CI 9.0 to 9.7). At 12 months, the overall difference between HbA1c improvement between the two groups was lower but remained a significant 1.0% (95% CI 0.4 to 1.5) 10.9mmol/mol (95% CI 4.4 to 16.4), P=0.001. In addition, it was found that children in the metformin group had a decreased insulin dose requirement of 0.2 units/kg/day throughout the 12-month period compared to those in the placebo group (95% CI 0.1 to 0.3, P=0.001).
The following study determined that children with T1DM with above average BMIs and taking metformin saw a significant improvement in vascular smooth muscle function compared to those not taking metformin. The study suggested that in addition to vascular health, metformin also improved HbA1c levels and reduced total daily insulin dose. It was found that improvements in both vascular function and HbA1c were the highest at 3 months. This is most likely due to medication adherence being the highest around 3 months.
Practice Pearls:
In children with above average weight and who were diagnosed with type 1 diabetes, metformin provides a significant improvement in vascular smooth muscle function.
Metformin provides a significant improvement in HbA1c levels in children with type 1 diabetes.
In addition to vascular health and HbA1c benefits, metformin further aids in reducing daily insulin dose in children with type 1 diabetes.
Anderson JJA, Couper JJ, Giles LC, et al. Effect of Metformin on vascular function in children with type 1 diabetes: A 12 month randomized controlled trial. 2017. J Clin Endocrinol Metab. 2017; 0: 1-16.

RCGP: When is a sick child seriously ill?

Adapted from RCGP, Acutely ill children by Ann Van den Bruel and Matthew Thompson June 14

A feverish child is very common and many of them consult the GP or go to the A and E department. Emergency admissions to hospital with febrile illness are increasing even though admissions for serious causes of infections are relatively rare at less than one percent of febrile children seen in primary care. These serious illnesses are mainly caused by pneumonia, urinary tract infection and many fewer by sepsis, meningitis and osteomyelitis. The trick is to be able to recognise the very few children with serious illnesses as soon as possible.  This is where it becomes so difficult as the early stages of illness are non specific.  Up to half of children with meningococcal disease, for example, are not recognised as such at first contact.

Parents often correctly realise that their child has a much more serious illness than usual, indeed this indicates 14 times the likelihood that there is a serious illness,  but other times their description of catastrophe bears little resemblance to what the doctor or nurse sees.

Some clinical signs are more useful than others. For instance if the temperature is over 40 degrees, the risk of serious illness is raised from 1% to 5%. Other important signs are cyanosis (blue lips), poor peripheral circulation (mottled hands and feet), rapid breathing, crackles on listening to the lungs, reduced breath sounds, meningeal irritation (causing a high pitched cry or a stiff neck), petechial bruising, (non blanching bruised looking rash), and reduced level of consciousness, ( drowsy or incoherent).

Combinations of features can help sort out potentially serious from not serious causes.

The only prediction rule that has been tested is this.  If one of these is present then there is a 6% chance of a serious infection:

the clinician has a gut feeling something is wrong, the child is breathless, the temperature is over 39.5 degrees, and there is diarrhea in a child aged 1-2.5 years.

If NONE of these are present however there is a 0% chance of a serious infection. That is,  no concern from a doctor, no breathlessness, a fever under 39.5 and no diarrhea aged 1-2.5 or diarrhea but in a child out with this age range.

Symptoms and signs can change over time of course so vigilance from the parents is still needed.


Meningococcal disease may be lethal. The trouble is that in the first 8 hours of the illness, it presents with the usual flu like symptoms of fever, headache and sore throat.  Typical symptoms of meningitis only occur after 13 to 16 hours. These include neck stiffness, rash, fits or loss of consciousness. They also don’t occur in all children with the illness. Other symptoms that can help are leg pain and also the less distinguishing skin pallor or blueness and cold hands and feet.


80% of all serious infections are due to pneumonia. This is obvious when you have an ill looking child, who is breathing fast and has a low oxygen saturation and on blood testing a raised CRP.

If a doctor has no concerns about the child AND there is no shortness of breath however, it is very unlikely that the child has pneumonia.

Heart rates and breathing rates can be raised in sick children but when this becomes abnormal is still a matter of debate.

If a doctor has concerns about a child, this raises the chances of serious illness from less than 1% to 11%.

Blood testing is rarely done in primary care but when done  perhaps in the A and E department, CRPs under 20 and procalcitonin levels under 0.5 ng/ml rule out serious infections.

Safety netting advice is particularly important if the diagnosis is not clear, there could be complications of a particular diagnosis or the child is at a higher risk of getting complications.

Although children are getting healthier, acute infections remain common, and parental concern leads to many presentations at the surgery or in A and E.  How to distinguish serious illness that needs quick intervention from non serious illness that can be managed at home remains a challenge.


Vegetable oil ingestion not so sunny after all

Adapted from BMJ 9 Feb 13 Use of dietary linoleic acid for secondary prevention  of coronary heart disease and death: evaluation of recovered data from the Sydney Diet Heart Study and updated meta-analysis. Christopher E Ramsden et al

Despite lack of evidence to the contrary I still see NHS dieticians telling patients to avoid naturally occurring saturated fat such as butter, cream and the fat in animal meats. This study didn’t get much publicity at the time so here it is again.

The question was, does increasing dietary omega 6 linoleic acid in the place of saturated fat reduce the risk of death from coronary heart disease?

What happened was that in the Sydney Diet Heart Study, a RCT done between 1966 and 1973, saturated fat (thought to produce heart attacks) was replaced by omega 6 fatty acids from Safflower oil ( vegetable oil and margarines, thought to be heart healthy). Although the blood cholesterol levels decreased in the intervention group, deaths from all causes, coronary heart disease and cardiovascular disease, all increased.

The subjects were all men aged 30-59 who had had a recent heart attack.  As an example, all cause mortality was 17.2% in the intervention group compared to 11.8% in the control group. Results for cardiovascular disease were similar.

It is mystifying that dietary advice telling people to swap lard for vegetable oils and butter for margarine is still going on. Very telling is that date that this study was done. The results would have been out by 1975.

Beware of alternative causes of neuropathy in diabetes

Diabetes in Control: Disasters averted

Not All Neuropathies in Diabetes are Caused by Diabetes
May 10, 2016

A woman, 57 years of age, type 2 diabetes, metformin 1,000mg twice daily for 12 years, came in with weakness, anemia, tingling of fingers and toes. Her A1C had always been below 7%. Some in my office thought she had developed diabetic peripheral neuropathy. I could not disagree, but I also knew metformin can cause vitamin B12 deficiency. I immediately ordered lab including a B12 level. Sure enough, her B12 was low. We recommended B12 lozenges, 500mcg daily, and her symptoms as well as her B12 levels improved. This was good news because neurological symptoms don’t always improve with B12 therapy, but hers did. (My comment: they need to be treated within six months of onset)
Lessons Learned:
• For patients taking metformin, check B12 levels at least annually.
• Consider recommending B12 supplementation to patients who take metformin, or at least teach of the possibility of this side effect.
• Teach patients who are on metformin therapy to eat foods high in vitamin B12 such as animal sources of foods including beef, poultry, seafood, eggs, dairy and foods fortified with B12.
• When a patient with diabetes presents with peripheral neuropathy, check vitamin B12 levels, and treat accordingly.

Gestational diabetics seven times more likely to get type two diabetes

From RCGP Brian McMillan et al

Reducing risk of type 2 diabetes after gestational diabetes: a qualitative study to explore the potential of technology in primary care.

April 2018

Although women who have experienced gestational diabetes have are seven times more likely to develop type two diabetes than other pregnant women, there is as yet no formal testing arrangement in primary care.

These women may benefit from annual Hbaic and ongoing dietary and advice on weight management.

If these women have a HbA1c of more than 42 they can become eligible for the National Diabetes Prevention Programme. Otherwise not.

Women in this situation were interviewed and told researchers that they would welcome advice regarding diet and the help of other women in the same situation. They said they would value technology to give them the information to enable personalised self management.

Diabetes awareness mama: managing mood changes in your type 1 child

This article is from the mother of a type one son who has recently started school. She discusses ways to help other parents of children in the same situation in her blog.

Managing mood changes
July 5, 2017
Hannah Foreman-Wenneker
Today I would like to open the doors on what goes on behind the scenes of a T1D child. What do they feel that we parents cannot see? What do they want to tell us but are too young to possess the vocabulary or verbalise their emotions? These, and many more questions, often race through my mind. Taking on the full time job of a pancreas isn’t just about calculating carbohydrates, night time blood tests or insulin pump therapy; it is equally as important to understand the side effects this disease has on your child’s brain and subsequently, personality.
It all starts with the physiology of diabetes. I will never be able to fully appreciate what our son physically and mentally feels when he experiences a hypo or hyper, I can only describe to you what I have been told. According to the experts: diabetics, when a child is having a hypo they feel weak, dizzy, confused and shaky. This fantastic 3 minute video of four woman describing how they physically feel and mentally react during a hypo is well worth your time.
It is quite common for a T1D to suffer from ‘hypo-unawareness‘, particularly in young children who are naturally less aware of their body and how it functions. Hypo-unawareness is physically dangerous, but it is also a mental battle for the patient and for those who care for them. When our son Noah, is feeling these symptoms his insulin pump will give me a warning alarm (caveat: there is a 20 minute, give or take, communication delay between his body and the pump) and I can treat the hypo for its physical effects.

There is no medical treatment for the mental effects of a hypo. In our experience, Noah morphs from an adorable kitten to a roaring lion in a nano-second. He goes from “Mummy I love you to the universe and back” to a vein-popping, red faced animal screaming inaudible words that make no sense anyway. Unlike typical child-like tantrums (which he naturally has too, yey! these appear as is if from nowhere.

Sometimes his behaviour is quicker to burst forth than the pump’s warning alarm and we can tell he is having a hypo simply from his monumental meltdown over inconsequential nothingness. Even though I know his diabetes is just ‘having a conversation with me’, I confess, I sometimes feel embarrassed when we are out in public. There are occasions when I have been in the supermarket or walking down the street and Noah’s diabetes wants to have another ‘chat’ with me. Millions of parents know the look you get from strangers on the street; you know the one, it appears that you cannot control your own child. I get those same looks but sometimes I just want to scream ‘you have no idea what he battles with inside!‘

Noah can also become confused during a hypo and he finds it difficult to concentrate. Whilst these are less fiery side-effects they cause me more long-term concern than the tantrum-style behaviour. I know the meltdowns will become easier as he gets older but he has already started school and now I find myself wondering how hypos will affect him in the future. How will Noah cope with T1D together with his education? Will it impact his academic ability? How can we help him now to learn to overcome these issues down the line?
According to this scholarly article we are already using the best possible therapy to support Noah’s mood and behaviour. ‘Continuous subcutaneous insulin infusion’ or insulin pump therapy has been very effective in reducing the frequency of hypos in T1Ds and the results show improved mood and behaviour changes in young children. So is that all that we have at hand to help? My answer to this is: I don’t think so.

Whilst it is notoriously difficult to measure neurological impact of T1D and, from what I can gather, is something that experts vary in opinion on, frequently the following cognitive elements are reported to be affected by T1D: intelligence (general ability), attention, processing speed, memory, and executive skills. I am not a scientist and I haven’t done any research into this, I am also only two years in as a T1D carer but my firm belief today is that all of these cognitive domains can also be greatly influenced by the parents, teachers, siblings, social circles, mentors and extended family etc. who surround the child.
And what about hypers? Someone once described to me that a hyper is like having a massive hangover, but without the nausea part. The patient is very thirsty, has severe headaches and lethargy. It isn’t rocket science to realise that these are not attributable feelings to a productive day at school or work.

For the last year, Noah experiences an (as yet) unresolved hyper every morning after his breakfast. His glucose levels soar, sometimes triple the amount of a non-T1D and try hard as we might, we haven’t yet fixed this ‘bug’ in his daily routine. Nevertheless, off he marches every morning to school, feeling like he drank himself under the table the night before. For now, I simply admire his strength but I worry about when he becomes a teenager, how will he find the will to keep concentrating on math, or history or grammar when he mentally becomes aware that he has a choice?
And speaking of teenagers, puberty is a notoriously challenging period for many diabetics, but I will leave this topic for another day, another year even. The underlying point here is that T1D presents enormous challenges both physically and mentally. Both require a bachelor degree level of understanding to deliver optimal short and long term care. Both take place behind the scenes and in front of a crowd but T1D is so massively misunderstood by many (including me before my son’s diagnosis) that raising awareness and understanding is a monumental challenge, but one that many can be proud to be passionate about.


Polycystic ovary syndrome is linked to autism in offspring

Cambridge University Autism Research Centre has found that compared to women who do not have polycystic ovary syndrome, women who do have this have about double the risk of having a child with autism.  The risk was slightly higher in male children compared to female children.

Cherskov A et al. Polycystic ovary syndrome and autism: At test of the prenatal sex steroid theory. Transl Psychiatry. Aug 1 2018. doi:10.1038/s41398-018-01867.