Showing posts with label Endocrinology. Show all posts
Showing posts with label Endocrinology. Show all posts

Monday, March 9, 2015

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kussmaul breathing pattern - description and causes

This type of breathing pattern was first described by Adolph Kussmaul, a german physician in 1874. He noticed that his patients with diabetic ketoacidosis had a pattern of breathing which he first labelled as having "air hunger".

In the Kussmaul type of breathing, the patient is breathing heavily i.e hyperventilating along with tachypnea.
So we will find that the amplitude of the breaths along with the rate will be increased.
There is usually no pauses between the breaths.

This is not specific for diabetic ketoacidosis. It can also appear in other types of severe metabolic acidoses e.g alcoholic ketoacidosis .

Saturday, April 26, 2014

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Diaxozide - mechanism of action


The diagram shows a beta cell of the islet of pancreas and will explain how local factors regulate secretion of insulin from it.
Glucose enters the cell via the GLUT-2 transporter. Inside the cell there is metabolism with the generation of ATP. This causes the ATP-sensitive K+ channel to close, as shown in A.
Closure of this channel leads to cell membrane depolarization. This in turn allows calcium ions to enter the cell via another calcium channel, shown in B. Increased intracellular calcium activates calcium dependent phospholipid protein kinase. This leads to exocytosis of insulin granules.

Diaxozide acts by opening the K+ channel. This leads to loss of K+ and causing membrane hyperpolarization. This prevents Ca2+ from entering, protein kinases are not activated and thus there is no exocytosis of insulin granules... 

Sunday, June 2, 2013

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Diabetes - 7 keys messages to the patients

1. Diabetes is self-managed.

Caring for diabetes is more than just taking a daily pill or doing your insulin injection. It may feel like a burden but the decisions you make about physical activity, what and when you will eat will affect both how you feel today and your future health and well-being.

2. Take diabetes seriously.

It is a multi-systemic disorder and indeed needs a lot of care. Since the symptoms and complications take time to appear you may think that it is a simple disease but it is not in reality!!!

3. Learn everything about the disease.

Since most of diabetes care is  about self-care, the more you know about it, the better you will be able to manage it. You can control your diabetes rather than letting your diabetes control you. If possible, try to get updated with latest developments in the field and read to drive away myths about the disease.

4. Your treatment will change over time.

Treatment of diabetes will eventually change over time. Changes in treatment do not mean that you have failed or that your diabetes is worse. It simply means that your body needs more help to keep your blood glucose level on target. Insulin therapy is part of the treatment and not a punishment.

5. Negative emotions are common.

It can be difficult to live with diabetes and researchers have shown that patients are about twice as likely to become depressed. Let your doctor know if your emotions are getting in the way of managing diabetes or enjoying your daily life. Do not hesitate to go for a psychological evaluation.

6. Step by step is the motto.

Diabetes often involves making changes in your food, exercise and other habits. It can quickly become too hard if you try to do it all at once. Start by choosing one thing that is important to you. Try to make small changes each day. It is likely that you will try different things along the way. Use what you learn about what does and does not work as a guide. Perfection is not the goal. It is what you do most of the time that counts.

7. Complications don't always happen.

You may have seen the toll of long-term complications on others. The good news is that these can be delayed or prevented by keeping your blood glucose and blood pressure levels in the target ranges. There are no guarantees, but you can greatly reduce your risk.

Living with diabetes is not easy. But with the help of your health care team and your family and friends, you can do it.

Wednesday, May 1, 2013

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Highest prevalence of Diabetes Mellitus

Figures till November 2012 show that the top 5 countries with the highest prevalence of Diabetes Mellitus are from the pacific islands. They may be the smallest islands but the epidemic of diabetes is one of the worst there. More than a third of adults in some of these countries have diabetes and the combined toll of complications, deaths and loss of income make diabetes a real threat not just to the individuals experiencing the disease but also to the economies of the countries themselves.

Above is an image showing the locations of the pacific islands.

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Top 10 countries with Diabetes Mellitus 2012

Data till November 2012 showed that together, these 10 countries make up 75% of the total prevalence of diabetes in the world.  Urbanisation and the accompanying changes in lifestyle are the main drivers of the epidemic in addition to changes in population structure where more people are living longer.

Friday, April 19, 2013

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Anemia in diabetic patients - Erythropoietin treatment?

If you encounter a normochromic and normocytic anemia in a diabetic patient, do not forget that it may be a case of erythropoietin deficiency. This deficiency can occur early in diabetic nephropathy (well before stage 5 of chronic kidney disease).

In adults, about 85-90% of the erythropoietin comes from the kidneys and 10-15% from the liver. It is produced by interstitial cells in the peritubular capillary bed of the kidneys and by perivenous hepatocytes in the liver. In cases of decreased renal mass, the level of erythropoietin falls and does not increase much in response to hypoxia (anemia). This occurs even if the liver is normal as the latter cannot compensate for the kidney's loss of function.

Since the availability of recombinant human erythropoietin to patients in 1989, anemia and transfusion requirements have become relatively  rare in patients on hemodialysis.
After adequate treatment with erythropoietin, studies have demonstrated that there is an:
1) enhanced exercise capability, presumably partly because of improved cardiac function with reduction in ventricular hypertrophy,
2) improved quality of life with improved physical performance, work capacity and cognitive capacity,
3) improved sexual function,
4) reduced rates of hepatitis and iron overload because of fewer transfusions.

All of the erythropoietin preparations are now referred to collectively as erythropoiesis stimulating-agents (ESAs). So far, intravenous route has been the sole route of administration and is given during hemodialysis but investigations are going on about the possibility of subcutaneous administrations.

With subcutaneous administration, peak serum concentrations of about 4% to 10% of an equivalent IV dose are obtained at around 12 hours, and thereafter they decay slowly such that concentrations greater than baseline are still present at 4 days.
The bioavailability of subcutaneous epoetin is around 20% to 25%. Nevertheless, subcutaneous application
is more efficient than IV application, allowing an approximately 30% dose reduction to maintain the same hemoglobin concentration.
Presumably, the early peak concentrations of epoetin after IV injection are inefficient, but the more prolonged elevation of hormone concentrations after subcutaneous application allows a more sustained stimulation of red cells production. Thrice-weekly administration has remained the most popular dosage frequency for both IV and subcutaneous administration, although once-weekly, twice-weekly and
seven-times-weekly (once-daily) dosing have all been used.

The hemoglobin target should be in the range of 11-12 g/dL and should not be greater than 13 g/dL.

Above is a diagram showing the change in hemoglobin level (blue line) with respect to different dosage of erythropoietin from 1991 till 2009 in an attempt to keep the hemoglobin in the target range. Hemoglobin level should be tested at least once monthly. 


Thursday, March 7, 2013

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Acanthosis nigricans - cause and significance

Acanthosis nigricans is a hyperpigmented velvety lesion usually found in the neck and the axillary region. It can also be seen elsewhere e.g. the belt line, creases over the dorsal surface of fingers. The palms and soles are typically not involved.

Pathologically, it is characterized by an increased number of melanocytes associated with hyperkeratotic epidermal papillomatosis.

It is strongly associated with insulin resistance but it is a non-specific condition and can also be found in obesity, polycystic ovarian syndrome, endocrine diseases like acromegaly and Cushing's syndrome, as well as some malignant tumours.

The severity of the acanthosis nigricans correlates with the degree of insulin resistance and the level of serum insulin.
The exact mechanism of its formation is still unclear but it is speculated that there are related IGF-1 receptors in the skin which are activated by ambient hyperinsulinemia.

If the insulting factor is removed, there may be a regression of the lesion.

Below are photos of a patient requiring more than 100 IU of insulin per day and despite dieting, the level of glycemia remained high.




It is an interesting case because it is an atypical location for acanthosis nigricans. The back of neck and axilla were free of any lesions.

Wednesday, March 6, 2013

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Classification of Diabetes Mellitus


Diabetes is divided into 4 different classes:

1) Type 1 diabetes (results from beta-cell destruction, usually leading to absolute insulin deficiency)
2) Type 2 diabetes (results from a progressive insulin secretory defect on the background of insulin resistance)
3) Other specific types of diabetes due to other causes, e.g. genetic defects in beta-cell function, genetic defects in insulin action, diseases of the exocrine pancreas (such as cystic fibrosis, pancreatitis) and
drug- or chemical-induced (such as in the treatment of HIV/AIDS or after organ transplantation)
4) Gestational diabetes mellitus (GDM) (diabetes diagnosed for the first time during pregnancy that is not clearly overt diabetes).

Wednesday, October 3, 2012

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Type 2 Diabetes Mellitus - Exercise benefits and regime

The positive benefits of exercise in a diabetic patient include:
1) cardiovascular risk reduction,
2) reduced blood pressure,
3) maintenance of muscle mass,
4) reduction in body fat and weight loss,
5) lowering plasma glucose (during and following exercise) and
6) increasing insulin sensitivity.

Also since the diabetics lack the normal glucoregulatory mechanisms, they are more prone to be affected by either hypo or hyperglycemia if exercising. That is why it is better to have the blood glucose monitored before, during and after the exercises.
It is not advised to do exercises if the blood glucose level is below 5.6 mmol/L or more than 14 mmol/L with ketones present.

The exercise regime recommended is as follows:
1) At least 150 minutes of moderate to vigorous exercise per week distributed over at least 3 days. One example of such a moderately intense exercise is brisk walking.
2) Ideally resistance training should also be done for 3 non consecutive days per week. e.g. small weight lifting.

Use of pedometer applications in mobile phone devices is also favoured. Studies have found that doing 10,000 steps per day is a good indicator of proper physical activity and will be beneficial on the long run.

Another important finding in a recent study found that in diabetic patients who did little or no exercise at baseline, cut their risk of death by 2/3 if they substantially increase their physical activity level over a period of 5 years.

Sunday, August 5, 2012

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Insulin - Structure

Insulin is a protein hormone. It was the first protein to be shown to have a precisely defined amino acid sequence. This work was done by Federick Sanger in 1953. 
As shown above in two colours, the insulin molecule consists of 2 peptide chains. 
a) The blue coloured chain is the A chain. It has 21 amino acids and a sisulphide bond within itself. 
b) The yellow colour represents the B chain. It is larger with 30 amino acids. 
Both chains are connected by 2 disulphide bridges. 
Porcine and bovine insulins differ from human insulin at 1 and 3 positions of the amino acids respectively. 

Friday, July 20, 2012

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Diabetes Mellitus - Definition / Criteria for diagnosis

Definition:
It is a group of metabolic disorders that is characterized by hyperglycemia which is due to a relative or absolute deficiency in insulin. There is usually a defect in insulin secretion, a defect in insulin action or a combination of both. 


Criteria for diagnosis:
1) An Fasting Plasma Glucose ≥ 7.0 mmol/L (126 mg/dL), 
2) A Plasma Glucose  ≥ 11.1 mmol/L (200 mg/dL) 2 h after an oral glucose tolerance test,
3) An HbA1c    6.5% or
4) A Random Plasma Glucose concentration   11.1 mmol/L (200 mg/dL) accompanied by classic symptoms of DM (polyuria, polydipsia, polyphagia, weight loss). 


Note:
1) Fasting means no calorie intake for the past 8 hours.
2) For the glucose tolerance test, we must use 75 g of anhydrous glucose dissolved in water.
3) The diagnostic HbA1c test should be performed using a method certified by the National Glycohemoglobin Standardization Program (NGSP) and standardized or traceable to the Diabetes Control and Complications Trial (DCCT) reference assay. The currently available assays are not accurate enough.
4) Random Plasma Glucose means without regard to time since last meal. 

Wednesday, September 21, 2011

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Diabetes insipidus - effect of desmopressin

This is a continuation of the main article Diabetes insipidus. It shows the effect of desmopressin in a case of central D.I.

The changes seen are:
1) decrease in urine output,
2) increase in urine osmolarity,
3) decrease in plasma osmolarity and
4) slight increase in body weight.

Desmopressin is 12 times more potent antidiuretic than ADH. It has a duration of action of around 8 hours and thus can be given in 3 divided doses per day. The intranasal route is preferred though the bioavailability is only 10-20%. Treatment is life long.
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Diabetes insipidus

Definition:
It is a syndrome characterized by the production of abnormally large volumes of dilute urine due to the decreased secretion or decreased action of AVP (arginine vasopressin). AVP is also commonly known as ADH i.e. Anti Diuretic Hormone.

Cause:
1) Central D.I - aka pituitary D.I or neurohypophyseal D.I.
2) Nephrogenic D.I

Central D.I occurs because of an inadequate release of ADH from the posterior pituitary. The usual causes are idiopathic, traumatic, iatrogenic (surgery,radiation), neoplastic, infective, granulomatous (TB,sarcoidosis) and congenital being a rarer cause.

Nephrogenic D.I is due to the resistance to ADH at the level of the collecting duct cell. The most common cause of resistance is the use of drugs like lithium (bipolar disorders) and amphotericin. But it can rarely be due to a congenital cause.

Pathogenesis:
The antidiuretic effect of ADH is achieved by increasing the hydroosmotic permeability of cells that line the distal tubule and medullary collecting ducts of the kidney. In the absence of AVP, these cells are impermeable to water and reabsorb little, if any, of the relatively large volume of dilute filtrate that enters from the proximal nephron. Thus there is production of large amounts of dilute urine.

Clinical features:
1) Polyuria - more than 50 mL/kg of urine per day (i.e. 3500 mL for a 70 kg man) with nocturia also,
2) Polydipsia due to excessive thirst,
3) Preference for ice water.

Investigations:
1) 24 hr urine sample will show a urine output > 50 mL/kg body weight,
2) 24 hr urine osmolarity will be < 300 mosmol/L,
3) Fluid deprivation test - no increase in urine osmolarity,
4) Administration of desmopressin at 0.03 μg/kg S.C or I.V and measurement of urine osmolarity 2 hr later -
An increase of >50% indicates severe pituitary DI, whereas a smaller or absent response is strongly suggestive of nephrogenic DI.

Treatment:
Desmopressin is a synthetic analogue of ADH and is a V2 receptor agonist that eliminates polyuria and polydipsia in central D.I. It can be given SC,IV,oral or intranasally. The last method is preferred and the dosage is 0.15-0.75 μg/kg.
The main side effect is water intoxication that is manifested as hyponatremia.

Thursday, September 15, 2011

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Whipple's triad - hypoglycemia diagnosis and treatment

 DIAGNOSIS 
Hypoglycemia can be diagnosed by whipple's triad which consists of:
1) symptoms consistent with hypoglycemia,
2) a low plasma glucose concentration measured by an accurate method,
3) relief of the symptoms when the plasma glucose level is raised.

 SYMPTOMS 
Symptoms of hypoglycemia are:
1) Neuroglycopenic symptoms like behavioral changes, fatigue, seizures, altered consciousness,
2) Adrenergic symptoms like palpitations, tremors, anxiety,
3) Cholinergic symptoms like sweating, hunger and altered sensations

The cut off value for hypoglycemia is 70 mg/dL which is equal to 3.9 mmol/L.

 TREATMENT 
Relief of symptoms can be done by:
1) an initial 20 g of carbohydrate containing fluid or food can be given if the patient can tolerate orally,
2) I.V glucose 25 g bolus at 2 mg/kg/min followed by 10 g/hr. 250 mL of 10% dextrose is better than 50 mL of 50 % dextrose as there is less thrombophlebitis.
3) Glucagon 1 mg subcutaneously or intramuscularly works as rapidly as dextrose and is a good method when no I.V access is available and the patient is unconscious but it will not work in drunk patient.

Below is a great infographic from Healthline .
Effects of caffeine on the Body
Last reviewed on: 2 September 2015

Friday, September 9, 2011

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Newly diagnosed Diabetes Mellitus type 2 - minimum assessment


1) Measurement of height, weight, waist, BMI
2) Measurement of blood pressure 
3) Examination of feet for pulses, loss of sensation to touch/vibration, signs of 
infection 
4) Measurement of visual acuity 
5) Urine tested for albumin, ketones and glucose 
6) Record made of current physical activity/recreational exercise levels, smoking 
history and alcohol consumption, addition of salt to prepared food 


If the resources and laboratory facilities are available then the following may be desirable. 
•  ECG as baseline 
•  Fasting blood lipids-cholesterol and triglycerides, HDL, LDL 
•  Serum urea and creatinine for those with proteinuria 
•  Retinal examination by fundoscopy 
•  Urine for microalbuminuria if dipstick –ve 
•  Glycosylated haemoglobin (HbA1c) 

Wednesday, August 10, 2011

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Insulin - action on peripheral cells


Insulin binds to receptor on target sites. These sites have an intrinsic tyrosine kinase activity that lead to receptor autophosphorylation and recruitment of intracellular signalling molecules. The latter result in widespread metabolic and mitogenic effects of insulin as shown in the diagram above.

Another effect is the activation of phosphatidylinositol 3 kinase that fastens the translocation of GLUT-4 containing vesicles to the cell surface. This is important to allow uptake of glucose by skeletal and fat cells.
When insulin action ceases, the transporter-containing patches of membrane are endocytosed and the vesicles are ready for the next exposure to insulin.


On the other hand, in the liver, this is not the mechanism of glucose uptake. Instead, it induces glucokinase, and this increases the phosphorylation of glucose, so that the intracellular free glucose concentration stays low, facilitating the entry of glucose into the cell by diffusion.

Insulin-sensitive tissues like muscles also contain a population of GLUT 4 vesicles that move into the cell membrane in response to exercise, a process that occurs independent of the action of insulin. This is why exercise lowers blood sugar.

Tuesday, August 9, 2011

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Insulin secretion - local regulation


The diagram shows a beta cell of the islet of pancreas and will explain how local factors regulate secretion of insulin from it.
Glucose enters the cell via the GLUT-2 transporter. Inside the cell there is metabolism with the generation of ATP. This causes the ATP-sensitive K+ channel to close, as shown in A.
Closure of this channel leads to cell membrane depolarization. This in turn allows calcium ions to enter the cell via another calcium channel, shown in B. Increased intracellular calcium activates calcium dependent phospholipid protein kinase. This leads to exocytosis of insulin granules.

Thursday, July 14, 2011

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Best insulin regimen

We have 2 classic regimens that have been used on a large scale.

1) Multiple component insulin regimen

Here, usually a basal insulin level is maintained by a long acting insulin like glargine insulin (lantus) injected at night. Then short acting insulin analogues are injected just after breakfast, lunch and supper. In total the patient has to do 4 injections per day.

2) Twice a day pre-mixed insulin

This is more commonly used. It consists of twice daily injected mixture of an intermediate acting insulin like NPH insulin and a short acting insulin or regular insulin in a ratio of 70:30.
2/3rd of the total insulin requirement is given in the morning and the remaining 1/3rd at night. The total number of injections is 2 per day.

For the patients' convenience, the second regimen seems better as he/she has to do only 2 injections but the first regimen i.e multiple component insulin regime is actually the better of the two. Studies have recently shown that a better HbA1c goal is reached with this regimen and that the risk of hypoglycemia is 10% less if carried out properly.

Monday, June 13, 2011

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Vitamin D - recommended level in blood, value for deficiency

The minimum recommended vitamin D level is 30 ng/mL but a range of 40-60 ng/mL has been put to guarantee sufficiency.
The vitamin D level actually refers to the level of 25-Hyhroxy-cholecalciferol i.e. 25[OH]D and not that of 1,25-Dihydroxy-cholecalciferol. 25[OH]D is the major storage form of vitamin D. Around 88% of it circulates bound to vitamin D-binding protein, 0.03% is free and rest circulates bound to albumin. It has a half life of around 2-3 weeks.
If this level is less than 20 ng/mL, it is considered as vitamin D deficiency.