Tag: research

Lower cholesterol may not better if you have neuropathy

kaitiscotland1 Comment

From Jende JME et al. Peripheral nerve damage in patients with type 2 diabetes. JAMA Netw Open. 2019;2(5);e194798

In type two patients who had diabetic neuropathy affecting the legs, low total cholesterol and low density lipoprotein cholesterol had more nerve lesions, impaired nerve conduction and more pain and disability than those with higher cholesterol levels.

Almost all type two diabetics will be advised to take statins to keep the cholesterol level down as this is generally accepted as improving the outlook for cardiac and circulatory conditions.

One hundred participants with type two diabetes were tested using magnetic resonance neurography. 64 had diabetic neuropathy and 36 did not.

My comment: Although this was not discussed in the abstract, I wonder whether those people with more advanced complications were being more intensively treated all round and thus had more/higher doses of statins, and so the relationship between low cholesterol and neuropathy severity was simple association, or whether there is a causative factor here. I am aware that statin neuropathy is believed to exist.

Higher blood pressure is linked to LESS cognitive decline

kaitiscotland4 Comments

From Streit S et al. Ann Fam Med 1 March 2019 and reported by Sarfaroj Khan UK Clinical Digest 13 March 2019

In my GP career treatment of blood pressure for the general population has become more intensive as time has gone on. This hasn’t always resulted in better long term outcomes overall. Indeed, the target systolic blood pressure, the upper measurement, has been moved from 130 to 140 in the last few years because of this.

A Dutch study of over a thousand patients over the age of 75 showed that those with a systolic blood pressure under 130 showed more cognitive decline than those with a blood pressure over 150 when they had mental functioning tests a year later.

Those with higher blood pressures had no loss of daily functioning or quality of life.

As aggressive blood pressure control in those with diabetes is standard treatment, it is worth knowing this. Perhaps further studies in this subgroup of patients would be worth doing. I have seen reports of impaired kidney function when blood pressure levels are “optimal” but low too.

Another study regarding blood pressure management reported in the British Journal of Sports Medicine indicates that blood pressure reduction of almost 9mm Hg in hypertensive patients when regular structured exercise is undertaken. This is of a degree similar to most anti-hypertensive medications. (Reported in BMJ 5 Jan 2019)

 

 

Eating carbs last gives lower blood sugar spikes

kaitiscotland5 Comments

From IDDT newsletter December 2018

A report in BMJ Open Diabetes Research and Care Sept 2017 shows that in type two diabetes, eating sugar and starch later in the meal halved the blood sugar spike after the meal compared with those who ate the sugar and starch first.

This study was done on 16 people who ate test meals of protein, vegetables, bread and orange juice. Those who were instructed to eat the bread and juice last also had 40% lower post meal glucose levels compared to those who ate all of the meal components in a mixed fashion.

My comment: This is a small study but easily reproducible with yourself and your blood glucose meter. If you do wish to eat sugar and starch best have these last, unless you are treating a hypo.

 

 

More fat = more kidney failure

kaitiscotland2 Comments

From BMJ 12th January 2019

Chang AR et al The CKD Prognosis Consortium BMJ 2019;364:k5301

Between 1970 and 2017 a huge number of people were assessed for fatness using body mass index, waist circumference and waist to height ratio. The outcome was that the fatter you get, the more your kidney function declines. This was true whether you started off  with normal or impaired kidney function.

The lowest kidney disease was seen in those with a BMI of 20 and this barely changed till a BMI of 25 was reached. After this was a linear progression. By the time your BMI is 40, you have double the risk of kidney function impairment.

The results were adjusted for age, sex, race and current smoking.

My comment: This is a new risk factor for obesity as far as I know.

 

 

 

Hypoglycaemia: the neglected complication

kaitiscotland3 Comments

Adapted from Hypoglycaemia: the neglected complication by Sanay Kalra et al.

Indian J Endocrinol Metab. 2013 Sep-Oct; 17(5): 819-834

Hypoglycaemia is an important complication of glucose lowering therapy in patients with diabetes mellitus. Attempts made at intensive glycaemic control invariably increases the risk of hypoglycaemia. A six fold increase in deaths due to diabetes has been found in patients with severe hypoglycaemia compared to those not experiencing severe hypoglycaemia.

Repeated episodes can lead to hypoglycaemia unawareness. Complications  of hypoglycaemia include stroke, heart attacks, cognitive dysfunction, retinal cell death and loss of vision. Apart from this there are the effects on quality of life regarding sleep, driving, employment, exercise and travel.

To maintain good glycaemic control, minimize the risk of hypoglycaemia and thereby prevent complications, there are steps that need to be taken: recognise risk factors for hypoglycaemia, use appropriate self monitoring of blood sugar, select treatment regimens that have little or no risk of incurring hypoglycaemia and teach health care professionals and patients how to avoid hypoglycaemia.

Although the DCCT showed that complications were reduced when blood sugars were brought under a HbA1C of 7%, other trials have noted a three fold risk of hypoglycaemia when the level is reduced under 6.5%. This tends to negate any improvements in long term complications.

Insulin users are most at risk. Those who have had diabetes for more than 15 years are particularly at risk. The DARTS study showed that the risk of severe hypoglycaemia was 7.1% for type one patients, 7.3% for type two patients and 0.8% for type twos on sulphonylureas. This causes increased cost for their healthcare as hospitalisation for around a week is needed in the average case.

The majority of hypos are due to medications but there are other potential causes such as: pancreatic or islet cell tumours, dietary toxins, alcohol, stress, infections, sepsis, starvation and excessive exercise.

In diabetics not eating enough food was the most common cause. Others were physical exercise, insulin miscalculation, stress, overtreating a high blood sugar, and impaired glycaemic awareness.

Nocturnal hypoglycaemia is seen in half of diabetic children, particularly under the age of 7. Dead in bed syndrome causes 5-6% of all deaths in type one youngsters.  Contributory factors are increased exercise that day or delayed meals.

In type two patients additional causative factors are alcohol ingestion and liver disease and duration of insulin over ten years. As in type ones there tends to be more hypoglycaemic unawareness as the person ages. In type twos  there is a 9 fold increase in deaths in those with hypoglycaemic unawareness.

Severe hypos in elderly patients increase the risk of dementia, functional brain failure and cerebellar ataxia. There are clear signs of neuronal death in specific brain areas at post mortem in these patients and a history of fits make these more extensive.

Hypos in elderly patients promote cardiac ischaemia. Arrhythmias are more likely due to catecholamine release during hypos. Prolonged QT intervals lead to increased heart rate, fibrillation and sudden cardiac death.  Inflammatory cytokines are released during hypos, abnormalities of platelet function and the fibrinolytic system occur.

Hypos can cause double vision, blurred vision and dimness of vision.  Blindness can occur due to retinal cell death.

Recurrent hypos make people feel powerless, anxious and depressed. Acute hypos cause mood swings, irritability, stubbornness and depression.  Quality of life scores are worse in patients with recurrent hypos.

Driving ability is affected by hypos. The affected driver can inadvertently cross lanes and speed and generally drive worse.

Hypos at night may be recognised by sleep disturbance, morning headaches, chronic fatigue and mood changes. In young children fits and bed wetting may occur.

Hypos at work can be awkward, embarrassing and frightening. Hypos are particularly dangerous for those who work at heights, underwater, on railway tracks, oil rigs, coal mines, handling hot metals or heavy machines.

Expert medical advice and planned action counselling can help workers. So can self blood glucose testing, healthy food options in canteens, flexible meal times, arrangements to carry and use emergency glucose/sugar, storage and disposal sites for medications and sharps, and time off for medical appointments. Work time and productivity due to hypos can be reduced and nocturnal hypos can also have a knock on effect the next day.

Hypos in children tend to be increased in summer months when they are more active. In adults, intense prolonged exercise following an episode of recent severe hypoglycaemia can damage skeletal muscle and the liver and can cause severe neurological symptoms.

Travelling long distances, particularly over times zones can cause insomnia, tiredness, stress, reduced appetite, nocturia,  gastric disturbance, muscle aching and headaches. Psychological symptoms include low mood, irritability, apathy, malaise, poor concentration. These deficits in both physical and mental performance can profoundly affect decision making.

The fear of hypos can affect patients more profoundly than the fear of long term complications.  Withholding of insulin can occur. Sometimes patients refuse to start it when they need it and sometimes they miss out their doses.

About 30% of type one patients are affected by hypoglycaemia unawareness and under 10% of type two patients are thus affected. Duration of insulin use is the main common factor.

Educating patients about how to detect, treat and prevent hypoglycaemia must be understandable to the patient and their family.

In 2013 the ADA recommended that insulin users test their blood sugars 6-8 times a day.

Basal insulin needs to be matched to the patients needs. If hypos persist, particularly overnight, switching to pump therapy may help.

Newer diabetic medications, which do not cause low blood sugars such as the gliptans and gliflozins, may be preferable in type two patients who have multiple co-morbidities, are elderly,  who live alone, are at high risk of falls, and who have hypoglycaemia unawareness or who otherwise could not effectively deal with a hypo.

 

 

 

Dietary calcium doesn’t make your bones stronger after all

kaitiscotland5 Comments

Although it is current practice to prescribe vitamin D and calcium together, particularly in post menopausal women, a six year study shows that the added calcium has no value.

The women were all over the age of 65 and had osteopenia. This is the stage before osteoporosis. 1,994 women were randomised to take zolendronic acid or placebo.  Bone mineral density was measured at the spin, total hip, femoral neck and total body three times at intervals.

The baseline BMD was unrelated to dietary calcium after controlling for age, height, weight, physical activity, alcohol intake, smoking and past HRT use when a cross section of women were studied.

Loss of BMD over the next six years was not related to the amount of dietary calcium ingested.

Bristow SM et al. Dietary Calcium intake and bone loss over six years in osteopenic post menopausal women. J Clin Endocrinol Metab. 2019 Mar 21.

My comment: Maybe time to ditch the calcium?

And while we are on the subject of bones, I’m pleased to say that another study has shown that high dose vitamin D supplementation does NOT increase kidney stone risk.

Over just over 3 years of taking 100,000 iu of vitamin D3 each month did not increase excess calcium in the blood or the onset of kidney stones in adults aged between 50 and 84 years.

This dose is equivalent to 3300 iu vit D3 a day, similar to what many of us in the know take.

158 people took part in the randomised trial. The number of people developing kidney stones was similar in each group and no one in the intervention group developed hypercalcaemia.  The groups self reported stones. No ultrasound was done which the authors say could have been more accurate.

Malihi Z et al. Monthly high dose vitamin D supplementation does not increase kidney stone risk or serum calcium: results from a randomised controlled trial. Am J Clin. Nutr. 2019 Apr 21

 

Liraglutide can improve fatty liver damage as well as blood sugars

kaitiscotland6 Comments

Adapted from Glucagon like peptide-1 receptor agonists for the management of obesity and non-alcoholic fatty liver disease: a novel therapeutic option. 

Gauri Dhir and Kenneth Cusi  Endocrinology/Metabolism Review Volume 66 Issue 1 2018

Obesity is a major risk factor for type two diabetes and a cluster of metabolic factors that lead to poor cardiovascular outcomes.  The amount of fat stored in the liver tissue closely mirrors insulin resistance and metabolic health.

Non alcoholic fatty liver disease (NAFLD) is now the commonest form of liver disease in the western world and can lead progressively to non alcoholic steatohepatitis (NASH), cirrhosis and hepatocellular carcinoma.

NAFLD is present in two thirds of obese people and promotes type two diabetes.  NASH is present in half of these. NAFLD is expected to become the most common cause of liver transplantation by 2020.

Pioglitazone and the newer drugs such as Liraglutide (Victoza) can be used, as well as various dietary therapies.

If a weight loss of 10% can be achieved, there is a significant improvement in the inflammatory process that results in cell death and fibrosis in NASH. But weight loss is difficult to achieve and maintain.  Pioglitazone can improve  NASH in two thirds of non- diabetic patients and by around half in those with diabetes or pre-diabetes.  Vitamin E has also been shown to have some success in non diabetic patients.

Liraglutide and drugs of the same class affect insulin secretion in response to meals, beta cell proliferation, inhibition of glucagon secretion, delayed gastric emptying, and making you feel fuller with less to eat.

These effects result in worthwhile clinical outcomes in overweight or obese patients whether they have diabetes or not. Body weight is reduced by at least 5% in 30% of patients and by at least 10% in 30% of patients. Over three years this can result in complete remission of the diabetes or pre-diabetes in 30% of the patients. Cardiovascular outcomes are also improved.

Triglyceride accumulation in the liver cells is the mechanism that has been recently shown to cause insulin resistant adipose tissue.  After 48 weeks of high dose Liraglutide (1.8 mg a day), resolution of NASH was seen on biopsy samples in 39% of the treated group compared to 9% in the placebo group.

The main side effects are nausea and diarrhea.  There could possibly be more gallstone development but no increase in pancreatitis.

High dose Vitamin D improves cardiovascular health markers

kaitiscotland3 Comments

Adapted from UK Medical News 17 July 2018

Several different health measures, all which improve your cardiovascular outcomes, have been found to result from high dose vitamin D supplementation. You are likely to need to take at least 4,000 iu a day though, depending on how much extra sunshine you are exposed to regularly.

A meta-analysis of 81 randomised controlled trials looked at almost one thousand patients randomised to taking supplements or to a control group who did not. The active and control groups were both roughly 5,000 each.  The durations of the trials varied but averaged out at ten months. The doses ranged from 400 iu a day to 12,000 iu a day. The average taken was 3,000 iu a day.

The outcomes were related to the blood level of vitamin D achieved. Levels had to be over 86 nmol/L to get benefits. You need to take over 4,000 iu a day to get vitamin D concentrations of 100 nmol/L or more.  My comment:This does mean that the minimum levels advised by the Scottish Chief Medical Officer last year are way too low to see the benefits discussed here.

So what extra benefits do you see?

lower systolic and diastolic blood pressure.

lower high sensitivity C reactive protein.

lower serum parathyroid hormone.

lower triglycerides.

lower total cholesterol.

lower low density lipoprotein.

high density lipoprotein increased.

All benefits were numerically small but did reach statistical significance. Cardiovascular outcomes were not measured directly, only blood markers and blood pressure.

Mirhosseini N et al. Vitamin D Supplementation. Serum 25(OH)D Concentrations and cardiovascular disease risk factors: A systematic review and meta-analysis. Front Cardiovasc Med. 2018 July 12.

 

 

 

 

Metformin improves blood sugar and vascular health in type one children

kaitiscotland4 Comments

 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.
Reference:
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?

kaitiscotland5 Comments

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.

Meningitis

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.

Pneumonia

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.