Diabetes Type 1

Type-1 Diabetes (T1DM)

Patient primer prepared by the BioSeek Endocrine Clinics Program

 So I (or my child) have type-1 diabetes. What do I do now?
You are not alone!

  • As many as 1:250 Americans (over 1 million people) have this disease too and the number grows with every passing year.  Finland has the highest frequency of T1DM in the world, and there, the disease is increasing in incidence at an annual rate of 3.6% compounding annually. The reason for this is obscure, however we believe that our increasingly hygienic society especially with respect to food and drink and possibly excessive antibiotic use may be important. We do not believe that cow milk or childhood vaccines are in any way involved based upon the available evidence, but some others do.

What is T1DM?
T1DM results from a deficiency of pancreatic insulin secretion.

  • T1DM is most often an immunological disease whereby a person’s own immune system attacks the pancreatic insulin secreting b cells as if they were “foreign” like a virus, and destroys them. This type of disease is called an autoimmune disease.
  • Insulin is a hormone that is secreted into the blood when food is eaten, where it directs the ingested nutrients to be stored in the body for later release as energy fuel in between meals. While diabetes is the failure to keep the blood sugar (glucose) within the narrow normal range of 70-200mgs/dl, T1DM is that type of diabetes caused by an inability to secrete enough insulin for the body’s needs.
  • The lack of insulin in T1DM causes the blood glucose levels to rise, and the kidney to excrete the excess glucose, taking with it salts and water from the body. This results in lots more urine than usual (polyuria) and thirstiness (polydipsia). Further, since food consumed by the patient cannot be stored in the body properly, weight loss is frequent, while the breakdown of fats from body stores overwhelms the body’s ability to convert them to energy. The excessive fatty acids released are diverted into the formation of ketones. At the same time, breakdown of body proteins (and release of glycerol from fats) is unhelpfully diverted by the liver and kidneys into even more new glucose (gluconeogenesis). If the diagnosis of T1DM is not made at this stage, the patients may get dehydrated with acid build-up in the blood, causing deep sighing breathing. This severe stage of the acute illness is called diabetic ketoacidosis (DKA). Whereas coma and even death can result, now days the diagnosis is usually made an early stage when non-urgent treatment can be initiated. Most times, initial treatment can be instituted in the Clinic and the patient not needed to be hospitalized.

How is T1DM treated?
The only way to treat the disease is to replace the deficient insulin (insulin is most often lost in the autoimmune destruction of pancreatic islet cells), by multiple daily injections of insulin, as follows.

  • A non-diabetic person secretes a steady low amount (basal) of insulin day and night, and secretes an additional amount (bolus) of insulin with every meal that is eaten. The amount of insulin in the food bolus depends largely on the amount of carbohydrates eaten with the meal or snack. In a normal day, a T1DM person needs about 0.5 –1.0 units of insulin per kilogram (1 kg = 2.2 lbs) body weight each day, an amount which will be lowered by exercise but increased by high food intake, stress or flu or pregnancy.
  • Basal insulin can be replaced by long-acting insulin injections or by a short-acting insulin taking continuously by insulin pump.
  • Two commonly used types of long acting insulin are NPH insulin which is taken twice daily, usually before meals, and glargine (LANTUS) insulin which may last the whole day from just one injection. Two injections of Lantus may be required each day in some, especially in young children. One big problem with NPH insulin is that there is a peak action at about 6-8 hours after it has been given, so that if food is not eaten around this time, low blood glucose levels (hypoglycemia) may result.
  • When insulin is given by a continuous subcutaneous insulin infusion (CSII) by pump, short acting insulins lispro insulin (Humalog) or aspart (Novolog) and more recently glulisine (Apidra) are given. Lispro insulin although a synthetic, man made hormone, has an action just like the natural form of insulin that non-diabetic people make. While a low levels of insulin occur normally during the early hours of sleep, most of us also have a natural rise in insulin during the early hours of the morning before waking. This is called the “dawn phenomenon” and is due to secretion of pituitary and adrenal hormones that appose the action of insulin. This rise is exaggerated in T1DM where additional insulin to oppose the rise cannot be made.
  • Bolus insulin can be replaced by recombinant (“bug made”) regular human insulin that has an action from 0.5 hours after it has been given to 4-6 hours later. Curiously, although this insulin is chemically identical to normal human insulin, it is slower to act and lasts much longer when injected under the skin because it aggregates. Humolog (lispro) insulin is slightly altered in structure from the natural human insulin but it acts just like natural insulin because it prevents aggregation after injection giving it an immediate effect and a short duration of action of 2-4 hours. Boluses of insulin are best taken before significant meals and snacks, in an amount that is dependent upon the blood glucose level and the quantity of carbohydrate in that meal. The bolus amounts which depend upon your before food blood glucose level and amount of carbohydrate to be eaten, are written out for you by the physician in the Clinic. Humalog insulin can thus be given before each of the three main meals (and snacks if by CSII), and sometimes at supper-time as well.
  • Combination multi-dose insulin (MDI) therapy:  The basal insulin can be given as by long acting insulin injections, however with all of them, absorption can be variable since they aggregate when injected, which makes them release insulin over a long period of time. Besides NPH (which acts over 0.5-1.0 days) and glargine insulin (which acts over 1.0-1.5 day period), ultra-lente insulin is another type that is similar to glargine but has a reputation for very irregular absorption. Lente is a mixture of two insulins, ultra-lente and semi-lente (which is like regular insulin) in a fixed proportion of 3:7. Since NPH insulin mixes readily with regular or Humalog insulins they can be taken up in the same syringe, but only if the short acting insulin is taken into the syringe first and NPH last and not the other way around. For convenience, Humalog and Novolog pens are useful for these multiple injections but CSII is the most convenient.
  • Continuous subcutaneous insulin infusion (CSII) or insulin pump therapy:  This method of insulin delivery most approximates the natural, non-diabetic state. It provides Humalog insulin at a basal rate, which can be adjusted to jog upwards in the early morning to cover the pre-dawn rise, and it allows for boluses to be given before meals and snacks as needed. The small plastic tube from the insulin pump that is attached to the body, is replaced once every 2-3 days. The advantages of insulin pumps over MDI are many. Most importantly, taking insulin by the insulin pump gives more flexibility with respect to day-time activities. Tighter diabetes control can be attempted without the same risk of hypoglycemic episodes with MDI. Meals can be eaten on the run, whenever they can be fitted in, instead of being fixed by time of day to cover the long acting insulin dose given hours before with conventional MDI replacement therapy. The number of injections required are also fewer. However what is not different is the need for close monitoring of the blood glucose levels throughout the day, and the need to eat a diet with appropriate contents of calories and carbohydrates.

Why is it important to control my blood glucose levels?
The higher the blood glucose levels, and the longer period of time that diabetes has been present, then the greater is the chance of developing diabetes complications.  The diabetes complications and control trial (DCCT) completed a few years ago by the National Institutes of Health (NIH) shows that the effort made to control blood glucose levels will greatly reduce such complications, the list of which includes:

  • Skin infections such as boils or vaginal candidiasis: These problems reflect diabetes control and are common to diabetes of all types. Once the diabetes is under control, the risk of developing these problems becomes much less.
  • Neuropathy: Chronic elevations of blood glucose can lead to damage of the sensory nerves to the feet and lower legs. Numbness and unpleasant or even painful sensations may be felt. Damage to the nerves of blood vessels may lead to a tendency of blood pressure to fall (postural hypotension) while damage to the nerves of the stomach (gastroparesis) and the intestine may result in eating problems and/or a tendency to diarrhea after eating. Some men also complain of impotence.
  • Nephropathy: Damage to the kidneys over time can lead to a loss of protein from the blood into the urine (proteinuria), an inability to concentrate urine properly at night, and later to kidney failure.
  • Eye Disease:  Opacities in the lens of the eyes (cataracts) can result from chronically raised blood glucose, while damage to the visual system (retina) can affect vision and even lead to blindness (retinopathy).
  • Micro-vascular disease: This lesion to the small arteries (arterioles) is common to all diabetes, but more with T1DM than T2DM. Blood vessels of the eye, kidney, lower legs and feet, and heart when affected cause the most concern.
  • Atherosclerosis: Common again to all diabetes is a tendency for wide spread atherosclerosis or “hardening of the arteries”, with an increased incidence of strokes, coronary heart disease and reduced circulation to the lower legs. This tendency can be compounded by elevations in blood lipids, especially LDL cholesterol.This problem is most common with T2DM rather than T1DM however.
  • Loss of self esteem: Some patients get needlessly down on themselves, and feel unnecessary helpless about their disease. This can prove to be self-fulfilling prophecy with under-achievements in areas of activities that if fact have nothing to do with having diabetes.

Wow! anything else?
Well there is one more thing. T1DM is usually an autoimmune disease (immune mediated T1DM), and other autoimmune diseases may afflict patients and their families. The list includes:

  • Thyroid disease:  Chronic inflammation of the thyroid occurs in 1: 4 girls and women with T1DM with lower frequencies in boys and men. This disease is called Hashimoto’s disease, and may results in non-painful swelling of the gland in the lower central neck (goiter), and a lower than normal amounts of thyroid hormone being made (hypothyroidism).  Lack of thyroid hormones results in dry hair and skin, tiredness, and sensitivity to the cold. Members of the family are commonly affected too, especially when female.
  • Gastric disease: Similarly, many patients lose their ability to made stomach acid (achlorhydria), especially if they also have thyroid disease. This causes no pain or problems outside of a tendency not to absorb iron from the diet which can lead to anemia. Later in life, these patients may not be able to absorb enough vitamin B12 either, which can also lead to anemia and nerve damage to the lower legs and feet.
  • Adrenal disease: This serious problem which is much less common results from the loss of ability to secrete normal amounts of adrenal hormones. Unusual falls in blood glucose and a muddy darkening of the skin may be seen, with muscle weakness and tiredness giving way to dehydration and faintness if not treated.
  • Ovarian disease: Uncommonly, autoimmune disease of the ovaries can occur, leading to diminishing periods and infertility.
  • Vitiligo:  This is a depigmenting skin disease, often seen in patches of white skin on the hands and around the eyes. The lesions do not hurt but can lead to bad burning from the sun.
  • Alopecia:  This skin problem is the loss of body hair. Like vitiligo, it is also an autoimmune skin disease.

This sure is a lot to contend with!
Perhaps, but the more you know about your diabetes and continue to value the diabetes care for yourself and your family, the less problems you will have in future. Indeed, there is no mental or physical activity that someone with T1DM should not be able to accomplish, provided that each situation is well thought out beforehand. Further, early warning signs of complications need to be monitored so that additional actions to head them off can be taken. This disease has a very different outlook than it once did, and the situation continues to improve. You should stay abreast of all of the research that is being done in this disease.

What do I need to look out for and what do I do about it when a problem is found?
Since diabetes is a lifelong disease, it is important to ensure that it is the immune mediated form of T1DM that you have. The finding of positive islet cell auto-antibodies (ICA, IAA, GADA and IA-2A) in the blood is one way to prove it, however the longer diabetes has been present, the more likely it is that these antibodies will have disappeared by the time of testing. Thus a negative test does not rule it out. Sometimes, if there is doubt, your ability to secrete insulin when given an oral glucose test (OGTT) may need to be determined.

  • Once T1DM is confirmed, time with a diabetes nutritionist and diabetes educator is useful.
  • Thyroid and adrenal auto-antibodies are measured (see above).
  • Insulin pump familiarity (video and booklet) is begun.
  • Growth in height and weight is recorded every 3 months, as is blood pressure.
  • A fasting blood lipid profile is done after diabetes has been controlled.
  • A urine is tested for micro-albumin yearly.
  • An opthalmologist’s examination is suggested every 2 years once puberty has begun.
  • Older patients may require EKGs and other tests.

Insulin injections are given into the upper arms, thighs, lower abdomen and bottom. The needle must be pushed in all the way and is best if it faces somewhat downhill, so that insulin does not leak out and not get into you. The bottles of insulin in use can be left out at room temperature. Store the unopened vials in the refrigerator.
You must learn how to measure blood glucose at home. There are many choices of monitors. Always bring your blood glucose record or meter into the clinic so it can be downloaded for analyses. BioSeek Clinics often provide One Touch Ultra Smart to their patients since the data can be quickly analyzed at the Clinic visit.

  • If you have positive thyroid antibodies (the disease is called Hashimoto’s disease or chronic lymphocytic thryoiditis), blood is taken for thyroid hormones at the next visit. If the hormones are low, a thyroid pill (Synthyroid @ 50-150mcg) is taken daily thereafter. If the test is normal, then it will be repeated yearly since there is a 5-10% chance of thyroid failure each year therafter.
  • If you have positive adrenal antibodies, then blood samples are taken for the pituitary adrenal trophic hormone (ACTH) and renin hormone levels. One or both are raised early when the adrenal glands are beginning to fail. Sometimes an ACTH stimulation test will need to be done. If the adrenal gland is failing, cortisone (a glucocorticoid) and fluorinef (a salt retaining hormone) will need to be taken daily.
  • If the blood pressure begins to rise and/or microalbuminuria appears, then an angiotensin converting enzyme inhibitor-class of drug (ACE inhibitor) such as Vasotec will be prescribed at 2.5-20 mgs daily.
  • If there is leakage of serum from a blood vessel in the eye, then laser therapy will be given to arrest it.

Is there any research going on that could make my life easier?
There is so much happening that you will find it hard to keep up with. Here are a few areas to get you started.

  • There is a lot of research development in the area of non-invasive glucose monitoring. Glucowatch is one of these. The current version that can read out blood glucose for about 16 hours (without pricks) has been released in the US but still needs refinements to avoid skin irritations from the current version.
  • Medtronics have a blood glucose monitors that involve repeatedly reading blood glucose levels through a plastic tube placed in you over a 1-3 day period, night and day. This can help identify low blood glucose levels at night that can result in a rebound hyperglycemia by the morning. The current version reads a bit lower than laboratory glucoses levels but the record can be helpful with trends.
  • Medtronics have just released a self implantable blood glucose monitoring device that can be used like an insulin pump and replaced every 2-3 days for continuous glucose monitoring.
  • Most of the pump companies are improving their product continually. Animas, Medtonics and Deltec have excellent pumps.
  • Many groups (Animas, Medtronics and Therasense) are trying to make implantable glucose sensors that can link with an insulin pump system to make an artificial pancreas. Unfortunately, the problem which has been tough to crack is that the body reacts to the sensor to wall it off, interfering with its’ function.
  • Work is being done on chemical methods of preventing damage from high blood glucose levels by preventing glycation of proteins (advanced glycated end products (or AGEs) of the body, especially in blood vessels.
  •  Pancreatic islet cell transplants are now usually successful. However there are two remaining problems to be solved; how to obtain enough human islets to transplant and how to avoid taking the large doses of immunosuppressive drugs needed to prevent rejection. The long term failure rates continue to be relatively high also. Many groups have begun studies into methods to grow islet cell in the laboratory from stem cells. Others are working on ways to create islet cells from other cells from the body such as skin cells or fibroblasts.
  • Efforts to prevent the disease through intervention studies are also underway.  For this, the relatives are screened for islet cell antibodies. The chances are about 3% for non-diabetic siblings. Those found to be positive are then tested (staged) for their ability to secret insulin by giving glucose into a vein (intra-venous) and then by measuring insulin in blood samples taken over the next 30 minutes (IVGTT).  According to the estimated risk of impending diabetes, various experimental interventions can be given. BioSeek has interests in several interventions which are best described during a Clinic visit.

Can I get help with all this?
If you are a patient in the BioSeek Clinics program, you can get expert help around the clock, seven days per week.

Freedoms Foundation: BioSeekEndocrine Clinics has established a foundation to further their ability to deliver services to less fortunate diabetic children and to foster research into diabetes and obesity related problems. Please ask if you are interested in helping the Clinic with this.