Thursday, November 13, 2014

10 Things About Metformin

- Metformin is currently the most commonly prescribed medication for type 2 diabetes; at least 4% of all Americans are taking it.

- Metformin is the only diabetes medication shown to reduce risk of heart disease vs no medication at all.

- Metformin is also prescribed for polycystic ovarian syndrome.

- Metformin interferes with digestion and often causes diarrhea.

- Roughly 5% of type 1 diabetics are taking metformin. In type 1 diabetics, metformin reduces insulin needs but those on metformin generally don't have lower A1cs or any difference in hypoglycemia rates.

- Metformin can be prescribed to prevent type 2 diabetes, and sometimes is.

- Metformin is available in brand and generic form, in pills and liquid.

- Metformin is in the medication class called "biguanides" and because another of the biguanides caused an awful lot of lactic acidosis when people took it and drank alcohol, drinking alcohol with metformin is not recommended. However, only about a dozen cases of lactic acidosis on metformin are known to have occurred. Ever.

- Although it's not an officially recognized side effect, I have met two people who've told me that taking metformin gave them brain fog. Metformin IS known to exacerbate vitamin B12 deficiencies, and a few studies have had inconclusive results when trying to figure out what effect metformin may have on dementia.

-Metformin was first described in an article in 1922, but was not FDA approved until 1995.

Wednesday, November 12, 2014

Diabetes affects the Brain

Shortly before I was diagnosed with diabetes, I began experiencing memory problems. They continued to get worse for months after I was diagnosed, and my memory has never returned to what it was before my diagnosis.

The changes in my memory were more life changing for me than diabetes- and y'all know diabetes was a game changer.

I don't know for certain whether or not diabetes was responsible, but I suspect it was.

Diabetes is associated with cognitive impairment in many domains as well as an increased risk of dementia in middle aged adults. DKA (which I was in at diagnosis) is associated with poorer cognitive performance for quite a while after the recovery from DKA. 

I have read a lot of studies in which diabetics do a lot worse on cognitive tests and school performance; I've read others where there is no difference, and even a couple of studies where diabetics outperformed their siblings in school (maybe diabetes messed with sibling homelife, but the diabetics and not their siblings were given some slack in school?)

However, whatever the cognitive performance, diabetes undeniably is associated with brain changes visible on brain imagery:
http://diabetes.diabetesjournals.org/content/early/2014/06/12/db14-0348.full.pdf+html

And of course, diabetes increases risk of stroke.

Tuesday, November 11, 2014

Lipodystrophy

Lipodystrophy- changes in fat composition as a result of injections, especially insulin injections- happens in two major types.

Lipohypertrophy occurs to at least a mild extent in the majority of people who have used insulin for five or more years; it tends to make itself known by a puffiness in the area(s) used most often for injection.

Lipoatrophy, where the fat from an area disappears, is much  rarer. I don't think anybody's done any good studies on lipoatrophy's incidence or prevalence, but my sense is that it occurs in 1-2% of long time insulin users.

Both types of lipodystrophy can change the insulin absorption. In most cases, it just makes it less consistant; in extreme cases it may prevent insulin absorption in those areas entirely. Recovery in a specific area may or may not happen after changing where the insulin is injected or infused, changing the insulin delivery method (from pump to shots or the other way around), or changing insulins.

Personally, I have so far experienced very mild lipohypertrophy on my thighs and that's it as far as visible lipodystrophy is concerned. However, I have gained a significant amount of fat because of being unable to walk nearly as much since my foot injuries in June, and I thought I'd try the Quick Sets again. Two out of two kinked, and this time I can't blame a lack of fat... I'm gonna blame scarring and/or abnormal density of fat tissue.

Monday, November 10, 2014

Interferon Alpha Treatment Can Cause Type 1 Diabetes

Years ago, I had dramatically elevated liver enzymes for a few months. While waiting for answers from the medical professionals, I went looking online for information about hepatitis, and on a hepatitis information board, I met a couple people who had developed type 1 diabetes within a year of being treated for hepatitis C; they said it was a risk of the treatment. As it turns out, the professional literature suggests that but has mostly hesitated to come out and say that the treatment definitely causes T1D.

Chronic hepatitis C infection is associated with an increased incidence of type 2 diabetes, which makes some sense because the liver is involved in so much of glucose regulation.
The only curative treatment for hepatitis C, interferon alpha treatment, is known to trigger autoimmune diabetes.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4138583/

When I  look up interferon and diabetes, however, I get a lot of results that have nothing to do with hep C.  Because an interferon, as it turns out, is a signal that cells send out to inform the rest of the body that they have been infected. And interferons are involved in the development of autoimmune disease, because in some autoimmune diseases- including type 1 diabetes- the organ that comes under attack from the immune system sends out interferons. Whether that pre- or post- dates the immune attack is uncertain- but this plays a part in the debate about the possibility that autoimmune diseases don't start out as autoimmune diseases. http://www.ncbi.nlm.nih.gov/pubmed/23966997
Genes for specific forms of interferon increase type 1 diabetes risk- although not enough to be anywhere close to the whole story. http://www.ncbi.nlm.nih.gov/pubmed/24402011

Sunday, November 09, 2014

Glucokinase

The typical gene for glucokinase can produce two different but very similar forms of glucokinase. One of these forms is typically produced in the brain and pancreas; the other form is produced in the liver.

This is because, among its other jobs, glucokinase is responsible for converting glucose to glycogen for storage in the liver, and its also responsible for signaling to our islet cells so that they know how much insulin and glucagon to produce.

People with one normal copy of the glucokinase gene and one copy that doesn't work as well generally have MODY 2- something whose classification as a diabetes is debatable. These people's bodies maintain blood sugar in a range as narrow as normal, but higher- they have a higher blood sugar set point that the body aims for. Attempting to treat it is difficult because of the body having an intact response to hypoglycemia, and that response kicking in at fairly high blood sugar levels. Fortunately, the risk of diabetes complications from MODY 2 is very low and so most doctors don't recommend treating it.
 Although it doesn't predispose people to type 2 diabetes, when type 2 diabetes happens in a person  who has MODY 2, it can be very hard to treat.

People with two copies of the glucokinase gene that don't work well may have neonatal diabetes, and there are also mutations of the gene that cause abnormally high production of insulin with hypoglycemia.

Saturday, November 08, 2014

Kimmelstiel and Wilson's Syndrome

Once upon a time, diabetic kidney disease was rare. Diabetes tended to either: occur so severely that death resulted from DKA or occur in elderly persons (or at the least, elderly for their time) who tended to die of infectious disease before kidney disease could catch up with them.

In December 1936, Clifford Wilson (1906-1997) and Paul Kimmelstiel (1900-1970) published a paper about kidney disease in the American Journal of Pathology called Intercapillary Lesions in the Glomeruli of the Kidney, describing kidney disease (with intercapillary lesions in the glomeruli) that primarily occurred in diabetics who also had hypertension and kidney disease signs and symptoms  such as albuminuria and edema. They speculated that diabetes might be the cause.

As an aside, the current wikipedia article mistakenly cites a different article by these two authors as the paper that first described diabetic nephropathy, but in fact their article on benign and malignant hypertension's only mention of diabetes is in noting that a small portion of autopsies showed pancreatic lesions.

Wilson and Kimmelstiel's description of diabetic kidney disease earned them the naming of the major type of diabetic nephropathy- Wilson-Kimmelstiel Disease.

However, it should be noted that the first paper mentioning that kidney changes could be seen in some diabetics was published in 1854.

Today, diabetic nephropathy is a major cause of death for type 1 diabetics; in some populations, it is the top cause but in most groups it ranks #2 or #3.

Source:
Landmark Papers in Nephrology, ed John Feehally et al. 2013

Friday, November 07, 2014

Things That Lead to Incorrect Type 1 Diabetes Diagnoses

-Not everybody with diabetes antibodies develops type 1 diabetes, and some people coincidentally have diabetogenic antibodies and non-type 1 diabetes. This is particularly true of people with only one positive diabetes antibody diagnosed with diabetes as adults.

- Many doctors incorrectly assume that diabetes in a child is type 1, and don't test anything else; or despite tests that don't support a type 1 diagnosis, don't know what else to think.
I always think of this when I remember a family I met on the DOC many years ago whose son was diagnosed with diabetes with a blood sugar over a thousand and was in a nonketotic hyperosmolar hyperglycemic coma at the time. He was antibody negative. But he was also ten years old. So they diagnosed him with type 1 diabetes anyways and put him on insulin. About a year (maybe two years?) later, he went off insulin and about six years later he's still off insulin.

- A lack of available other diagnoses. Type 2 diabetes is by definition diabetes caused by an insulin secretory defect on top of a background of insulin resistance. However... that description does not hold true for a very large portion of adults with type 2 diabetes diagnoses, and many doctors are reluctant to make a diagnosis of diabetes that's not type 1 or type 2, particularly because the other available diagnoses are other specific diabetes and gestational diabetes, and it's often impossible to say what specific other the diabetes is. So if they're pretty sure there's not an insulin secretory defect on top of insulin resistance, and they're pretty sure it's diabetes... then you may get a type 1 diagnosis.

- The c-peptide test of insulin production needs to be performed when a person is NOT in DKA, and has a blood sugar that's only slightly high to be a good measure of insulin producing capacity.

Based on studies of c-peptide levels in people with longstanding diagnoses of type 1 diabetes, I think that at least 5% of type 1 diabetes diagnoses are incorrect.

Thursday, November 06, 2014

Frank Rizzo, Former Mayor of Philadelphia, was a diabetic

Frank Rizzo, who was head of the Philadelphia police department from 1967 to 1971 and mayor from 1971 to 1983, was diagnosed with diabetes around age 19 (he served one year in the Navy and was discharged because of his diabetes diagnosis).

I believe he had type 1 diabetes despite the fact that he himself referred to it in public as "mild diabetes" because:
-after his death, his doctor mentioned that he took insulin
-he was diagnosed no older than 20
-it was severe enough a case of diabetes that it was diagnosed in 1939 (when mild cases didn't tend to get diagnosed) and to get him discharged from the navy in a time of war- which would not have been the case if he could have gotten away with controlling it via diet.

If I am correct, then Rizzo lived with type 1 diabetes for just over fifty years; he died in 1991 at the age of 70.

I have,  TBH, mostly heard negative things about Rizzo's mayorship- particularly about police brutality and racism. Nonetheless, he was a remarkable figure... and he had diabetes during all of the famous parts of his life.

Wednesday, November 05, 2014

People Normally Have Blood Sugar

I have heard people say that  somebody "has blood sugar" when they mean "has diabetes". Today, that  sounds ignorant; two hundred years ago it would have been scientific opinion.

I have not been able to tease out which sources are accurate with regards to who did what in terms of figuring out that in general blood DOES contain sugar. However, the following people seem to have been involved:

Hermann von Fehling (1812- 1885) a German chemist, after whom Fehling's solution is named. He lived in what is now Germany, and he studied chemistry. His solution is used to test for the presence of sugar, and it was still in use as the primary test for sugar when insulin came around. He developed it in 1848, and appears to have been aided in part by

Barreswill 1817-1870 a photographer, who was working on developing chemicals for better colors in pictures; finding out what chemicals changed color in reaction to what  was useful to Fehling, who may have been a friend of his.

Claude Bernard (1813-1878) whose experiments on animals demonstrated that the liver releases sugars in the blood stream even in animals that haven't been consuming sugar, and that beyond  a shadow of a doubt, sugar in the blood is normal. His main experiments with the pancreas were with digestive juices; he suspected diabetes was caused by signaling issues between the liver and brain.

Tuesday, November 04, 2014

Worms

One of the more strange sounding books  that comes up when I search my library's catalog for books on autoimmune diseases is An Epidemic of Absence, which I have not read. It takes the cleanliness hypothesis- the idea that the immune system makes more errors and creates more disease when there are fewer antigens in the environment (an antigen is any surface that antibodies may target)- and blows it further.
According to the book jacket and reviews, it claims that the absence of internal parasites  is bad for us!
So I didn't read it.

However, I was reminded of it when I came across this study today. The article about the study mentions that type 1 diabetes rates are lower in areas where it is common for humans to have worms. For the study, the researchers took worms from sheep bile ducts, and then injected the worms into a strain of mice that's been bred to have autoimmune diabetes. In the control group, 80% of the mice developed diabetes; in the group that was given worms, 16% developed diabetes.